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Topics
from the book,
Gluten Problems and Solutions
by Stephen Gislason MD
Dr
Stephen Gislason's Preface
What is Gluten?
What is Celiac Disease?
Allergy
Digestive Tract Permeability
Diseases Related to Celiac Disease
Gluten-Free
Diet Revision
Celiac Diagnosis
Gluten Psychiatry
Dermatitis Herpetiformis
Celiac Disease & Cancer
This discussion of
celiac disease and other gluten-related disorders is continued in the
book. You can order the book separately or as part of
The Gluten Rescue Starter
Pack.
An
eBook edition is also available.
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Celiac Disease - Description & Incidence
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References from the Medical Literature
Coeliac disease research and clinical practice: maintaining momentum into the
twenty-first century.
- Author
Ferguson A
Address University of Edinburgh, UK.
Source Baillieres Clin Gastroenterol, 1995 Jun, 9:2, 395-412
Abstract Recent research shows that each word in the definition of coeliac disease,
permanent gluten sensitive enteropathy, must now be reviewed, revised or reinterpreted.
Permanent--but there are now well documented cases of acquired disease, and perhaps also
partial recovery of gut gluten tolerance. Enteropathy--gluten sensitivity is expressed in
a spectrum, with a mild form seen as normal architecture with high count of
intraepithelial lymphocytes. Gluten--the provoking agent--Investigators are intensively
working to identify the precise toxic sequence, and to establish how this will link in
with new genetic information. Mechanism of sensitivity? or hypersensitivity?--Critical to
this is new knowledge on the modulation and regulation of immunity to intestinal antigens,
including gliadin. A hypothesis is presented, as to the pathogenesis of gluten-sensitive
enteropathy, which combines concepts of oral tolerance and of the regulation of expression
of delayed type hypersensitivity reactions in the gut mucosa.
The coeliac disease task force " Free from Gluten," " Improved
knowledge to cure coeliac disease".
- Author
Greco L; Percopo S
Address Department of Pediatrics, University Federico II, Naples, Italy.
Source Acta Paediatr Suppl, 1996 May, 412:, 25-8
Abstract Gluten has recently been introduced into the diet of the Mediterranean and
European population, but a considerable proportion has not adapted to this change and has
developed intolerance to gluten. At least one million EEC citizens are gluten intolerant.
In Italy each year 12 million ECU is spent in the diagnosis of uncomplicated gluten
intolerance, 10 million ECU for complex diagnosis and 32 million ECU for long-term
complications and malignancies. The total financial load of gluten intolerance, in its
present state, is about 150 million ECU/year in Italy. Four million ECU is actually needed
to develop a genetic probe, which may make the population screening feasible. A National
Task Force "Free from Gluten" has been set up by the Italian Coeliac Society to
stimulate fund-raising activities supporting genetic and basic research on gluten
intolerance.
Striking differences in the incidence of childhood celiac disease between Denmark and
Sweden: a plausible explanation.
- Author
Weile B; Cavell B; Nivenius K; Krasilnikoff PA
Address Department of Paediatrics, University of Copenhagen, Gentofte Hospital,
Denmark.
Source J Pediatr Gastroenterol Nutr, 1995 Jul, 21:1, 64-8
Abstract Among 771 children (381 Swedish and 390 Danish) investigated between 1972
and 1989 because of suspected celiac disease (CD), 179 proved to have the disease.
Surprisingly only 24 CD patients were found among the Danish children, compared with 155
in the Swedish group, despite the close ethnic, geographical, and cultural background of
the two populations. The Swedish CD children were diagnosed at an earlier age than the
Danish children (mean, 1.5 vs. 5.5 years). The symptoms of the Swedish patients were
dominated by failure to thrive (93 vs. 71%), whereas a higher proportion of the Danish CD
patients suffered from stomach pain (21 vs. 5%). Breast-feeding habits were comparable.
The estimated content of gliadin in the officially recommended diets of the two countries
in 1987 differed substantially, the Swedish diet containing more than 40 times more
gliadin than the Danish (4,400 vs. 100 mg) at the age of 8 months, and 4 times more (3,600
vs. 900 mg) at the age of 12 months. The Danish infant diet differed significantly from
the Swedish in containing a larger amount of the lower gluten-containing rye flour. The
earlier introduction of food items with a high gluten content in the Swedish compared with
the Danish diet seems to be an obvious explanation for the great difference in incidence
and symptomatology of CD between the two populations.
Coeliac disease in childhood.
- Author
Littlewood JM
Address St. James's University Hospital, Leeds, UK.
Source Baillieres Clin Gastroenterol, 1995 Jun, 9:2, 295-327
Abstract Coeliac disease usually presents in infancy or early childhood with
diarrhoea, vomiting and interference with weight gain and growth. Withdrawal of dietary
gluten is followed by resolution of the symptoms and signs and restoration of normal
weight gain and growth; the characteristic subtotal villous atrophy of the jejunal mucosa
also recovers. Later re-introduction of dietary gluten will lead to a return of the
jejunal mucosal abnormality in the majority and to clinical relapse in many but not all.
The severity and timing of both are variable and 5% of children initially considered on
clinical, biopsy and gluten response evidence to have coeliac disease appear to develop
permanent tolerance to gluten, although mucosal relapse may occur years after the
re-introduction of dietary gluten in a minority, emphasizing the need for long-term
follow-up. Although a diagnostic and subsequent follow-up jejunal biopsy are necessary to
confirm the diagnosis, anti-gliadin IgA and IgG, anti-reticulum and anti-endomysium
antibodies are now almost totally reliable in identifying children who have coeliac
disease and are valuable in monitoring the adequacy of gluten withdrawal. Dietary
compliance is frequently poor and regular supervision by a paediatric dietitian is needed;
indeed, lifelong supervision to ensure gluten withdrawal is essential to reduce the chance
of developing later gastrointestinal malignancy.
Gender and clinical presentation in adult celiac disease.
- Author
Ciacci C; Cirillo M; Sollazzo R; Savino G; Sabbatini F; Mazzacca G
Address Gastrointestinal Unit, Medical School, University Federico II of Naples,
Italy.
Source Scand J Gastroenterol, 1995 Nov, 30:11, 1077-81
Abstract BACKGROUND: Celiac disease may present in various forms. This study aimed
to investigate whether gender affects the clinical presentation of the disease in adult
celiac patients from the Mediterranean area. METHODS: This study retrospectively analyzes
data collected in all adult patients with celiac disease (n = 195) seen during the past 13
years at the Gastrointestinal Unit of the Federico II University of Naples, Italy.
RESULTS: In these series of patients the ratio of women to men was 3.33. Age at diagnosis
was lower in women that in men (p < 0.05). Except for asthenia, all signs and symptoms
were more frequent in women than in men. Hypochromic anemia was the most commonest finding
in women and was 40% more frequent in women than in men (p < 0.001). Dyspepsia was
twice as frequent in women as in men (p < 0.05); genital disorders were reported by 44%
of women and by no men. Recent weight loss or low body mass index was the commonest
finding in men. About 60% of men and women reported diarrhea; among patients without
diarrhea, the prevalence of hypochromic anemia differed between sexes (p < 0.05),
occurring in about 80% of women. CONCLUSION: This study shows that the clinical
presentation of celiac disease is not the same in men and women. The disease is not only
more frequent in women than in men but is also more severe and more rapid. The data also
suggest the need to look for celiac disease in patients with unexplained hypochromic
anemia.
High prevalence of undiagnosed coeliac disease in 5280 Italian students screened by
antigliadin antibodies.
- Author
Catassi C; RÂatsch IM; Fabiani E; Ricci S; Bordicchia F; Pierdomenico R;
Giorgi PL
Address University Department of Paediatrics, Ancona, Italy.
Source Acta Paediatr, 1995 Jun, 84:6, 672-6
Abstract Many cases of coeliac disease are currently undiagnosed. We carried out a
pilot study on screening for coeliac disease in a school population. The screening
protocol consisted of three parts: (1) IgG and IgA antigliadin antibody (AGA) assay; (2)
antiendomysium antibody and total serum IgA determinations; (3) jejunal biopsy. A total of
5280 students aged 11-15 years (71.7% of the eligible population) underwent the first
evaluation; 113 subjects performed the second tests and 35 of these needed the third
investigation. Coeliac disease was diagnosed in 23 cases, most of which were atypical or
silent forms. The prevalence of undiagnosed coeliac disease was 4.36 per 1000 screened
subjects (95% CI 2.58-6.14) and 5.03 per 1000 (95% CI 3.41-6.65) in the general
population. The ratio of known to undiagnosed cases was 1 to 6.4. This high prevalence of
undiagnosed coeliac disease raises a number of problems that require further evaluation.
Prevalence and diagnosis of celiac disease in IgA-deficient children.
Author Meini A; Pillan NM; Villanacci V; Monafo V; Ugazio AG; Plebani A
Address Department of Pediatrics, University of Brescia, Italy.
Source Ann Allergy Asthma Immunol, 1996 Oct, 77:4, 333-6
- Abstract
BACKGROUND: Reported frequencies of celiac disease in selective IgA
deficiency in childhood vary widely and this is probably due to the different
characteristics of the patients studied and to the different criteria used for intestinal
biopsy: all patients or only those with symptoms of malabsorption. Diagnosis of celiac
disease is of considerable importance in IgA deficiency because of its increased frequency
and also because avoidance of dietary gluten permits elimination of the symptoms and
complications of celiac disease. OBJECTIVES: To obtain a more reliable estimate of the
incidence of celiac disease in childhood IgA deficiency jejunal biopsies were performed in
65 consecutively diagnosed IgA-deficient children whose parents consented. Some clinical
and laboratory parameters including IgA-antigliadin and IgG-antigliadin antibodies were
evaluated to predict their usefulness in selecting IgA-deficient patients for intestinal
biopsy. METHODS: All IgA-deficient patients had serum IgA levels below 5 mg/dL and
salivary IgA below 0.5 mg/dL. Jejunal biopsy was performed using a peroral Watson capsule
and IgA-antigliadin and IgG-antigliadin antibodies were performed by an ELISA assay.
RESULTS: Biopsy findings of severe villous atrophy permitted diagnosis of celiac disease
in 7.7% (5/65 children). IgG-antigliadin antibody levels, elevated in 16 patients
including all five celiacs, were the best parameter for predicting celiac disease and gave
no false negatives. CONCLUSIONS: The 7.7% frequency of celiac disease observed in these
IgA-deficient children is about 20 times higher than in the general Italian population,
and the lowest among the studies biopsying all patients; this is probably attributable to
the presence of a substantial proportion of healthy children (20/65) and very few (2/65)
with autoimmune disorders. The elevated sensitivity and negative-predictive value of
IgG-antigliadin antibodies lead us to suggest that positive IgG-antigliadin antibodies can
be used to select IgA-deficient children for jejunal biopsy with a very low probability of
missing celiac disease while allowing a drastic reduction in the number of biopsies
performed.
Is celiac disease a lifelong disorder?
- Author
Schmitz J
Address Department of Pediatrics, HÈopital des Enfants Malades, Paris.
Source Clin Invest Med, 1996 Oct, 19:5, 352-6
Abstract That celiac disease is a lifelong disorder was suggested by clinical case
records and was considered to have been demonstrated through the widespread use of
intestinal biopsies by the end of the 1950s. It was clear that the mucosal lesions
observed in children and adults were identical and responded similarly to gluten
withdrawal. In fact, in 1970 the European Society for Paediatric Gastroenterology and
Nutrition instituted the practice of a challenge after diagnosis. A relapse of clinical
symptoms and of the intestinal lesions after gluten was reintroduced into the diet
demonstrated the "permanent" nature of sensitivity to gluten in children with
celiac disease. Twenty-five years later, the permanence of the sensitivity of the
intestinal mucosa to gluten is again a matter of debate. Several lines of evidence,
gathered during recent years, show that celiac disease is not always a lifelong condition.
First, the long-term follow-up of children with proven celiac disease shows that 10% to
20% of them become "tolerant" (defined on clinical, biological and histologic
grounds) to gluten during adolescence. Second, it has also been shown, in individual
cases, that the mucosal lesions typical of the disease may appear during adulthood. Our
increasing knowledge of the long-term evolution of the disease suggests that celiac
disease develops and, in some cases, fades in a predisposed group of people with
intestinal sensitivity to gluten, which is probably a common condition. The factors
leading to the appearance or disappearance of the disease, however, are still unknown.
Celiac disease is a lifelong disorder.
- Author
Chartrand LJ; Seidman EG
Address Division of Pediatric Gastroenterology, Sainte-Justine Hospital, Quebec.
Source Clin Invest Med, 1996 Oct, 19:5, 357-61
Abstract Celiac disease has always been considered a permanent condition. A relapse,
defined on the basis of mucosal changes, occurring within 2 years of reintroducing gluten
to a patient's diet (challenge) has been taken as confirmation of the permanence of the
disease. Some observers have questioned whether the disease is permanent, since long
periods of unexplained clinical remission occur, mainly among adolescents. However, the
presence or absence of symptoms has no correlation with the histologic activity of the
disease or with the results of serologic tests. With very few exceptions, patients in whom
celiac disease is diagnosed during their childhood eventually have a relapse. However, in
some cases, many years may elapse before a relapse; therefore, the 2-year limitation is no
longer considered valid. On the other hand, there have been anecdotal observations that
some patients eating a normal diet containing gluten appear to have experienced a
"natural recovery." This recovery is partial and probably temporary, since there
is evidence that celiac disease can be present in a latent form. Long-term randomized
studies, in which morphometric and ultrastructural measurements are taken, that show
villous integrity, the absence of abnormal inflammation and a lack of long-term
complications of a diet containing gluten are needed before the current
"zero-gluten" approach to celiac disease is altered. The individual variation in
the extent and time course of celiac disease does not contradict the evidence that the
disease persists throughout life, actively, silently or latently. Currently, there is no
justification for recommending long-term consumption of gluten for either children or
adults with celiac disease.
GIT Permeability
Lymphocytic gastritis and gastric permeability in patients with celiac disease .
- Author
Vogelsang H; Oberhuber G; Wyatt J
Address Department of Gastroenterology and Hepatology, University Clinic of Internal
Medicine IV, Vienna, Austria.
Source Gastroenterology, 1996 Jul, 111:1, 73-7
Abstract Lymphocytic gastritis is associated with celiac disease. Gastric
permeability can now be assessed by a sucrose test, and intestinal permeability measured
by a lactulose/mannitol test is increased in untreated celiac patients. The aim of this
study was to prospectively compare gastric and intestinal permeability with histological
changes of the stomach and small bowel in patients with celiac disease. METHODS: Gastric
and intestinal permeability were measured by oral or duodenal (during endoscopy)
administration of a triple sugar solution containing 20 g sucrose, 10 g lactulose, and 5 g
mannitol in 100 mL water in 43 adult patients with celiac disease (28 without diet) and in
30 healthy controls. Endoscopical biopsy specimens were taken from the antrum and distal
duodenum and investigated for intraepithelial lymphocyte counts. RESULTS: Urinary sucrose
excretion decreased after duodenal administration (n = 8) as opposed to oral
administration and thus measured gastric permeability in celiac disease. Gastric
permeability was elevated in 60% of the celiac patients and correlated with antral
intraepithelial lymphocyte counts. Intestinal permeability (measured by a
lactulose/mannitol test) was also elevated in 69% of the celiac patients and correlated
with duodenal intraepithelial counts. CONCLUSIONS: There is a high prevalence of
lymphocytic gastritis in untreated celiac disease associated with elevated gastric
permeability. Celiac disease seems to be a general disorder of the gastrointestinal tract
associated with disturbed permeability.
Gut permeability to human alpha-lactalbumin, beta-lactoglobulin, mannitol, and
lactulose in celiac disease .
- Author
Kuitunen M; Savilahti E
Address Children's Hospital, University of Helsinki, Finland.
Source J Pediatr Gastroenterol Nutr, 1996 Feb, 22:2, 197-204
Abstract Our objective was to examine the permeability of the gut to protein
macromolecules and sugar probes and their possible association in celiac disease patients.
We studied the permeability to human alpha-lactalbumin, beta-lactoglobulin, mannitol, and
lactulose on 46 occasions in 33 celiac disease patients in various phases of the disease;
in addition, mannitol and lactulose permeability was studied in 18 healthy controls.
Lactalbumin absorption was detected in 19 of 42 patients tested, more often in celiac
disease patients with villous atrophy than in those with normal jejunal biopsy (p = 0.01).
Higher absorption of lactalbumin was found in patients with subtotal villous atrophy than
in those with normal biopsy (p = 0.02). beta-lactoglobulin was found in four of 42
patients tested. Less mannitol was absorbed by patients with either subtotal or partial
villous atrophy than by those with normal histology (p = 0.001 and 0.006, respectively).
Lactulose recovery was higher in newly diagnosed patients and patients with subtotal
villous atrophy than in controls (p = 0.007 and 0.03, respectively). The
lactulose/mannitol ratio was higher in newly diagnosed patients and patients with villous
atrophy than in controls (p = 0.002 and 0.002, respectively). The correlation between
permeability to lactalbumin and mannitol and lactulose was poor. We conclude that
permeability to proteins and sugar molecules is abnormal in celiac disease patients with
mucosal damage and that they probably reflect different mechanisms of penetration.
Follow-up of celiac disease with D-xylose breath test.
- Author Casellas F; De Torres I; Malagelada JR
- Address
Digestive System Research Unit, Hospital General Vall d'Hebron, Barcelona,
Spain.
- Source
Dig Dis Sci, 1996 Oct, 41:10, 2106-11
- Abstract
Hydrogen breath tests (H2-BT) are commonly used to diagnose carbohydrate
malabsorption. Specifically, the H2-BT with D-xylose has been shown to be as valid as the
traditional urinary test for the recognition of intestinal malabsorption. We have now
investigated the H2-BT with D-xylose in the follow-up of patients with celiac disease.
Seventeen patients with celiac disease established clinically and confirmed by jejunal
biopsy were studied. H2-BT was performed before and after treatment with a gluten-free
diet for at least five months. Alveolar breath samples were obtained before administering
orally 25 g of D-xylose and thereafter at 30 min intervals for 5 hr. Samples were analyzed
for H2 by chromatography. Simultaneously, the 5-hr urinary excretion of D-xylose was
determined by colorimetry. Gluten removal significantly decreased the H2 delta change
(from 56.5 +/- 5.9 ppm to 32.2 +/- 8.8, P < 0.05). A similar decrease was observed in
the area under the curve (P < 0.05). Conversely, urinary D-xylose excretion increased
significantly (P < 0.05). Eleven of the 17 celiacs clinically improved after treatment.
The H2-BT normalized in every patient who entered remission on the gluten-free diet,
whereas the urinary D-xylose excretion remained abnormal in six of them. In the six
nonresponder patients the H2-BT remained high in five, whereas urinary D-xylose excretion
paradoxically normalized in 2. We conclude that H2-BT with D-xylose is a useful and
practical test for the follow-up of celiac disease and is simpler and more reliable than
the urinary D-xylose test.
Screening for celiac disease in first-degree relatives of patients with celiac disease
by lactulose/mannitol test.
- Author Vogelsang H; Wyatt J; Penner E; Lochs H
- Address
Department of Gastroenterology, University of Vienna, Austria.
- Source
Am J Gastroenterol, 1995 Oct, 90:10, 1838-42
- Abstract
OBJECTIVES: In first-degree relatives of celiac patients, the risk of
oligosymptomatic celiac disease is elevated. These individuals therefore also have a
higher potential for malignancy or nutritional deficiencies. Lactulose/mannitol
permeability is increased in untreated celiac patients and has been recommended to screen
for celiac disease. We investigated the usefulness of a lactulose/mannitol home test kit
for screening first-degree relatives home test kit for screening first-degree relatives of
celiac patients. METHODS: The lactulose/mannitol test was performed at home by 111
first-degree relatives. These subjects received the test kit from celiac index patients,
were instructed by an information sheet how to carry out the test, and were asked about
their symptoms by questionnaire. When lactulose/mannitol permeability was abnormal,
endomysial antibodies were tested by immunofluorescence. Any relatives with positive
endomysial antibodies were then biopsied. To investigate the specificity of the
lactulose/mannitol test for celiac disease, 40 patients with nonspecific gastrointestinal
symptoms were tested. RESULTS: Lactulose/mannitol permeability was elevated in 34 (31%)
relatives, but only nine (8%) of those relatives showed positive endomysial antibodies.
Flat mucosa was found in all nine relatives after biopsy. The prevalence of celiac disease
was much higher (42%) among 12 relatives who contacted the outpatient clinic themselves
because of symptoms. Seventy-one percent of the remaining 21 relatives with elevated
permeability demonstrated normal intestinal permeability at a control test within 1 yr.
CONCLUSION: By combining the lactulose/mannitol test with endomysial antibody testing, we
have developed a good strategy for use in screening for celiac disease among first-degree
relatives.
Assessing the site of increased intestinal permeability in coeliac and inflammatory
bowel disease.
- Author
Teahon K; Somasundaram S; Smith T; Menzies I; Bjarnason I
Address Department of Clinical Pharmacology, University of Newcastle upon Tyne.
Source Gut, 1996 Jun, 38:6, 864-9
Abstract The precise site of intestinal permeability changes in patients with
coeliac and inflammatory bowel disease is unknown. AIMS: To design a non-invasive
technique for the localisation of altered gastrointestinal permeability to 51chromium
labelled EDTA (51CrEDTA). The method depends on comparing and defining concentration/time
profiles in serum of a series of simultaneously ingested indicators with a well defined
absorption site (3-0-methyl-D-glucose (jejunal indicator), 57cobalt labelled vitamin B12
(ileal indicator), and sulphasalazine (caecal-colonic indicator)) in relation to
simultaneously ingested 51CrEDTA. SUBJECTS: Five normal controls, six patients with
untreated coeliac disease, five with Crohn's ileitis, and five with pan-ulcerative colitis
underwent study, which entailed the simultaneous ingestion of the above four test
substances followed, during the next 24 hours, by timed serial collection of urine and
serum for marker analysis. RESULTS: Urinary excretion of 51CrEDTA was significantly
increased in all patient groups. Analysis of serum appearances and profiles of the markers
suggested that the increased intestinal permeation of 51CrEDTA took place in the diseased
jejunum in patients with coeliac disease, predominantly in the ileum in Crohn's disease
and in the colon in the patients with pan-ulcerative colitis. CONCLUSION: A new
non-invasive technique has been assessed that permits the localisation of the site of
permeability changes with the gastrointestinal tract.
Non-Invasive and Screening Tests
Screening for celiac disease: a prospective study on the value of noninvasive tests.
- Author
Vogelsang H; Genser D; Wyatt J; Lochs H; Ferenci P; Granditsch G; Penner E
Address Department of Internal Medicine IV (Gastroenterology and Hepatology,
University of Vienna, Austria.
Source Am J Gastroenterol, 1995 Mar, 90:3, 394-8
Abstract OBJECTIVE: Celiac disease is frequently diagnosed in patients with
nonspecific abdominal symptoms. Therefore, highly sensitive, specific, and simple
noninvasive screening tests are needed. METHODS: This study compared the usefulness of
IgG- and IgA-antigliadin antibodies, IgA-endomysial antibodies, and intestinal
permeability in diagnosing celiac disease in 102 adult patients with nonspecific abdominal
symptoms. In addition, all patients underwent small bowel biopsy as a gold standard for
the diagnosis of celiac disease. RESULTS: Forty-nine patients were ultimately diagnosed as
having celiac disease because of flat mucosa. Flatulence and signs and symptoms dating
back to childhood were more frequent and abdominal pain less frequent (p < 0.05) in
celiac disease but were not helpful for screening. IgA-endomysial antibodies showed a
sensitivity and specificity of 100%; an altered intestinal permeability had also a 100%
sensitivity, but only 55% specificity. IgG- and IgA-antigliadin antibodies' sensitivity
(73% and 82%, respectively) and specificity (74% and 83%, respectively) were much lower.
Combining the two antigliadin antibodies did not significantly improve the sensitivity and
specificity. CONCLUSIONS: Our data show the advantage of IgA-endomysial antibodies for
screening of celiac disease except in the case of patients with IgA-deficiency or
dermatitis herpetiformis. In these patients, the permeability test could improve
noninvasive differential diagnosis.
IgA antigliadin antibodies as a screening method for nonovert celiac disease in
children with insulin-dependent diabetes mellitus.
- Author
Calero P; Ribes-Koninckx C; Albiach V; Carles C; Ferrer J
Address Endocrinology and Gastroenterology Units, La Fe Children's Hospital,
Valencia, Spain.
Source J Pediatr Gastroenterol Nutr, 1996 Jul, 23:1, 29-33
Abstract One hundred forty-one children with insulin-dependent diabetes mellitus
were screened for serum immunoglobulin A (IgA) antigliadin antibodies by means of an
enzyme-linked immunosorbent assay (ELISA) method. None of them had gastrointestinal
symptoms, and no major nutritional disturbances were detected except for a girl with
moderate growth delay. Twelve patients with positive IgA antigliadin antibodies on two or
more consecutive measurements underwent a small intestinal biopsy; four of them had a
subtotal villous atrophy, and celiac disease was diagnosed; in another patient, a partial
villous atrophy was observed. Children suffering from both diabetes and celiac disease
showed an onset of diabetes at a younger age than did nonceliac patients. Prevalence of
celiac disease in the screened population is 2.85%, which is higher than in the general
population of the Comunidad Valenciana (one in 2,500 live births).
Preliminary results from follow-up of a large-scale population survey of antibodies to
gliadin, reticulin and endomysium.
- Author
Johnston SD; Watson RG; McMillan SA; McMaster D; Evans A
Address Department of Medicine, Queen's University of Belfast, Northern Ireland.
Source Acta Paediatr Suppl, 1996 May, 412:, 61-4
Abstract Coeliac disease is often under-diagnosed, particularly in cases which are
atypical or asymptomatic. OBJECTIVE: The aim of this study was to comprehensively assess
the prevalence and clinical profile of adult coeliac disease in our community. METHODS:
One-hundred-and-thirteen subjects from the most recent MONICA (multinational MONItoring of
trends and determinants in Cardiovascular disease)1991/2 survey with positive serology
were followed up 3 years after initial screening and assessed by means of (i) a clinical
questionnaire, (ii) screening blood tests, and (iii) jejunal biopsy. RESULTS: Forty-six
subjects (21 male, mean age 51 years) have been followed up to date. Prior to follow-up,
two of these subjects were diagnosed as having coeliac disease. Ten (3 male, mean age 51
years) of 44 subjects had enteropathy. Three of these 10 subjects were relatively
asymptomatic, 3 had folate deficiency and 3 had iron deficiency. Thus 12 of the 1823
initially screened had enteropathy consistent with coeliac disease. CONCLUSIONS: Coeliac
disease is more prevalent than previous estimations and was found to be at least 1 in 152.
Diagnostic value of various serum antibodies detected by diverse methods in childhood
celiac disease.
- Author
Sacchetti L; Ferrajolo A; Salerno G; Esposito P; Lofrano MM; Oriani G;
Micillo M; Paparo F; Troncone R; Auricchio S; Salvatore; F
Address Dipartimento di Biochimica e Biotecnologie Mediche, Universita Frederico II,
Napoli, Italy.
Source Clin Chem, 1996 Nov, 42:11, 1838-42
Abstract The diagnostic performances of antiendomysium IgA detected on monkey
esophagus and human umbilical cord smooth muscle, of antireticulin IgA, and of antigliadin
IgA and IgG were calculated in 74 children with celiac disease (CD) or other
gastrointestinal disorders. We also compared four methods for gliadin antibody detection.
With a diagnostic specificity of 100%, diagnostic sensitivity was 94% for antireticulin
IgA, 93% for antiendomysium IgA when detected on human umbilical cord smooth muscle, and
97% when detected on monkey esophagus. The diagnostic sensitivity for gliadin antibody was
highest with an ELISA procedure, followed by fluorogenic detection (94% for IgG, 91% for
IgA, 97% with IgA and IgG combined). Because of its high diagnostic sensitivity and ease
and speed of use, the combined antigliadin IgG and IgA antibody assay is suitable for
screening large groups of patients. In IgG- or IgA-positive cases, the more demanding and
more specific antiendomysium IgA evaluation is required to confirm suspected CD.
Serum and salivary antigliadin antibodies and serum IgA anti-endomysium antibodies as
a screening test for coeliac disease.
- Author
Rujner J; Socha J; Barra E; Gregorek H; MadaliÆnski K; WoÆzniewicz B; Giera
B
Address Department of Gastroenterology, Child Health Centre, Warsaw, Poland.
Source Acta Paediatr, 1996 Jul, 85:7, 814-7
Abstract Serum and salivary IgA and IgG antigliadin antibodies were determined by an
enzyme-linked immunosorbent assay in 18 children with villous atrophy and 30 children on a
gluten-free diet for coeliac disease in whom normal intestinal mucosa was found. Serum IgA
anti-endomysium antibodies were also determined by an immunofluorescence method in these
children. Serum IgG antigliadin and IgA anti-endomysium antibodies had the highest
sensitivity (100 and 94.4%, respectively), followed by serum IgA antibodies to gliadin
(72.2%), salivary IgA antigliadin (61.2%) and IgG antigliadin (50%) antibodies. The
highest specificity was found for serum IgA anti-endomysium (100%) and IgA antigliadin
(96.6%) antibodies and salivary IgA and IgG antigliadin antibodies (93.3%), while serum
IgG antigliadin antibodies were found to be least specific (63.3%).
Is small bowel biopsy necessary in adults with suspected celiac disease and IgA
anti-endomysium antibodies? 100% positive predictive value for celiac disease in adults.
- Author Valdimarsson T; Franzen L; Grodzinsky E; Skogh T; StrÂom M
- Address
Department of Internal Medicine, Faculty of Health Sciences, University
Hospital of LinkÂoping, Sweden.
- Source
Dig Dis Sci, 1996 Jan, 41:1, 83-7
- Abstract
The comparative diagnostic value of IgA anti-endomysium and IgA antigliadin
antibodies in adults with histologically confirmed celiac disease is reported. Sera from
144 adult patients (without concurrent dermatitis herpetiformis or IgA deficiency) who
underwent small bowel biopsy were analyzed for both IgA anti-endomysium and IgA
anti-gliadin antibodies. Nineteen patients (13%) had celiac disease. The presence of IgA
antiendomysium antibodies had a sensitivity of 74% and a specificity of 100%. The positive
and negative predictive values were 100% and 96%, respectively, and the diagnostic
accuracy was 97%. In contrast, IgA anti-gliadin antibodies had positive and negative
predictive values of 28% and 96%, respectively, with a diagnostic accuracy of 71%. Based
on these data, we suggest that small bowel biopsy is not necessary to diagnose celiac
disease in symptomatic adults with IgA antiendomysium antibodies. Due to a negative
predictive value of 96%, some symptomatic adults lacking anti-endomysium antibodies will
not be correctly diagnosed without small bowel biopsy.
-
A comparison of diets with and without oats in adults with celiac disease
- Author
Janatuinen EK; Pikkarainen PH; Kemppainen TA; Kosma VM; JÂarvinen RM;
Uusitupa MI; Julkunen RJ
Address Department of Medicine, Kuopio University Hospital, Finland.
Source N Engl J Med, 1995 Oct 19, 333:16, 1033-7
Abstract
BACKGROUND. Wheat, rye, and barley damage the small-intestinal mucosa of patients with
celiac disease; maize and rice are harmless. The effects of a diet containing oats are
uncertain. METHODS. In a randomized trial, we compared the effects of gluten-free diets
without oats and with oats (with a goal of 50 to 70 g per day from three sources: two
types of wheat-starch flour mixed with an equal amount of oats, muesli containing 60
percent oats, and rolled-oat breakfast cereal). Fifty-two adults with celiac disease in
remission were followed for 6 months and 40 with newly diagnosed disease for 12 months.
Endoscopy with duodenal biopsy was performed at the beginning and end of the study.
RESULTS. The mean (+/- SD) oat intake in the oat group was 49.9 +/- 14.7 g per day at 6
months for patients in remission and 46.6 +/- 13.3 g per day at 12 months for patients
with newly diagnosed disease. The oat and control groups did not differ significantly in
nutritional status, symptoms, or laboratory measures. Patients in remission, regardless of
diet, did not have worsening architecture of the duodenal villi or increased
mononuclear-cell infiltration. All the patients with new diagnoses were in remission at
one year, except for one in the control group. Six patients in the oat groups and five in
the control group withdrew from the study. CONCLUSIONS. Moderate amounts of oats can be
included in a gluten-free diet for most adult patients with celiac disease without adverse
effects.
Diseases Related to Celiac Disease
The major complications of coeliac disease.
- Author
Wright DH
Address University Department of Pathology, Southampton General Hospital, UK.
Source Baillieres Clin Gastroenterol, 1995 Jun, 9:2, 351-69
Abstract Neoplasms constitute the major complication of coeliac disease, and
high-grade T-cell lymphoma of the small intestine (enteropathy-associated T-cell lymphoma)
is the most common neoplasm in this category. HLA genotyping indicates that in patients
with enteropathy-associated T-cell lymphoma have the coeliac disease associated DQA1*0501,
DQB1*0201 phenotype, although additional HLA-DR/DQ alleles may represent risk factors for
lymphoma development. Molecular biological and immunohistochemical studies have shown that
the intestinal mucosa distant from the tumour contains clonal populations of small T
cells, often of the same clone as the high-grade T-cell lymphoma. These findings suggest
that enteropathy-associated T-cell lymphoma arises in the setting of coeliac disease and
evolves from reactive intraepithelial lymphocytes through a low-grade lymphocytic neoplasm
to a high-grade tumour, which is usually the cause of the presenting symptoms. Most cases
of chronic ulcerative enteropathy (ulcerative jejunitis) are probably part of the same
disease process. If the ulceration occurs at a time when the neoplastic T-cells are of a
low grade, morphological recognition of tumour cells in the ulcers may be impossible.
Carcinoma of the pharynx and oesophagus, and adenocarcinoma of the small intestine, are
increased in frequency in patients with coeliac disease. The increased risk of carcinoma
of the oesophagus may be related to vitamin A deficiency. A number of reports have
indicated an increased prevalence of various types of chronic hepatitis in patients with
coeliac disease, but no coherent view of the cause of this association has emerged.
Similarly, patients with coeliac disease have been reported to have various forms of
fibrosing lung disease of uncertain causation. In recent years, there have been several
reports, mainly from Italy, of a syndrome of epilepsy and bilateral brain calcification
occurring in coeliac patients. The pathogenesis of this condition is not known and its
prevalence in other communities is uncertain. Splenic atrophy occurs frequently in
patients with coeliac disease and is related to the severity of the disease and degree of
dietary control. Splenic atrophy predisposes to infection with capsulated bacteria,
although mortality studies indicate that infection with these organisms is not a major
cause of death in patients with coeliac disease.
Non-malignant complications of coeliac disease.
- Author
Holmes GK
Address Department of Medicine, Derbyshire Royal Infirmary, Derby, UK.
Source Acta Paediatr Suppl, 1996 May, 412:, 68-75
Abstract Patients with coeliac disease are at increased risk of developing
complications which increase morbidity and mortality. Emphasis on malignant complications
has often overshadowed the non-malignant risks, which have received relatively little
attention, although some of these can be very troublesome and even life-threatening. This
article points out that a large population of unidentified or neglected coeliac patients
is at potential risk. The challenge is to identify this group by case-finding or screening
programmes in selected populations, so that they can be offered a gluten-free diet and
other treatments which will not only improve general health but may also prevent or reduce
the development of health problems. The non-malignant risks are outlined and bone and
neuropsychiatric disturbances considered in more detail because of recent developments in
these areas.
Bone remodeling indices and secondary hyperparathyroidism in celiac disease.
- Author
Keaveny AP; Freaney R; McKenna MJ; Masterson J; O'Donoghue DP
Address Department of Gastroenterology, St. Vincent's Hospital, Dublin, Ireland.
Source Am J Gastroenterol, 1996 Jun, 91:6, 1226-31
Abstract
OBJECTIVES: To determine the prevalence of hypovitaminosis D and secondary
hyperparathyroidism (SHPT) and to assess bone turnover by using markers of bone formation
and resorption in celiac disease (CD). METHODS: Forty-three patients with CD were
investigated: group 1, newly diagnosed celiacs (n = 19); group 2, treated celiacs
responding histologically to a gluten-free diet (n = 16); group 3, refractory celiacs,
unresponsive to a gluten-free diet and immunosuppressive therapy (n = 8). Serum was drawn
for intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], ionized calcium
(Cai), total alkaline phosphatase (AP), and biochemical markers of bone formation:
procollagen I carboxyterminal propeptide (PICP) and osteocalcin (Oc). Urinary indices of
bone resorption, deoxypyridinoline (DPD), pyridinoline (PyD), and hydroxyproline (OHP),
were measured in a 2-h fasting urine. In 22 patients, computerized tomographic scan for
bone mineral density (BMD) was performed. RESULTS: The prevalence in groups 1, 2, and 3,
respectively, of hypovitaminosis D (<50 nmol/L) was 58%, 25%, and 88%, and the
prevalence of SHPT ( 5.4 pmol/L) was 25%, 19%, and 25%. Bone resorption markers were
significantly elevated in all groups, and bone formation indices were elevated in the
newly diagnosed celiacs compared with a group of healthy adults. Low BMD (T-score greater
than -1 SD unit) was found in 68% of patients assessed; 36% of patients had a T-score
greater than -2.5 SD units. CONCLUSIONS: Hypovitaminosis D and SHPT are common in newly
diagnosed and refractory celiacs but are less common in those who respond to a gluten-free
diet. Newly diagnosed patients have a high bone turnover state with elevation of both bone
formation and resorption indices. Those with refractory disease demonstrate a remodeling
imbalance with high bone resorption.
Body composition and bone mineral density in untreated and treated patients with
celiac disease.
- Author
GonzÆalez D; Mazure R; Mautalen C; Vazquez H; Bai J
Address SecciÆon OsteopatÆias MÆedicas, Hospital de ClÆinicas, Buenos Aires,
Argentina.
Source Bone, 1995 Feb, 16:2, 231-4
Abstract Body composition and bone mineral density (BMD) were studied by X-ray
absorptiometry in 20 untreated and 12 treated women with celiac disease, as well as in 85
age-matched control women. Untreated patients had a significantly lower body weight, fat
mass, lean tissue mass and BMD at the lumbar spine and total skeleton compared to controls
(p < 0.001 for all parameters). Treated patients had also a significantly lower body
weight (p < 0.01) fat mass (p < 0.05) and bone mineral density at lumbar spine and
total skeleton (p < 0.05) compared with controls, but lean tissue mass was not
diminished. However, treated patients had a significantly higher body weight, fat mass and
BMD of the total skeleton compared with untreated celiac patients (p < 0.01 for all
parameters). Serum alkaline phosphatase levels were increased in untreated patients but
serum 250HD was normal. In conclusion, celiac disease causes a global and almost universal
reduction of fat mass and BMD. The results of this cross-sectional study suggest that
osteopenia does not seem to be completely restored by adequate treatment. Alteration of
vitamin D metabolism was not the cause of osteopenia in the majority of patients.
Neurological complications of celiac disease: a rare but continuing problem.
- Author
Muller AF; Donnelly MT; Smith CM; Grundman MJ; Holmes GK; Toghill PJ
Address University Hospital, Nottingham, England.
Source Am J Gastroenterol, 1996 Jul, 91:7, 1430-5
Abstract Neurological complications are a recognized but unusual manifestation of
celiac disease. We present here our experiences with four current cases. Age of patients
at presentation with neurological signs varied from 7 to 67 yr. In one patient, the
neurological disability developed before the diagnosis of celiac disease, whereas, in the
other three, it occurred from months to 16 yr after the diagnosis had been established.
One patient died of rapidly progressive neuromyopathy. The other three patients had
combinations of cerebellar and posterior and lateral column abnormalities. All four
patients developed neurological complications despite a strict gluten-free diet. In three
of four patients, there was no improvement in duodenal histology on this diet. Treatment
with vitamin B12, folic acid, or vitamin D failed to reverse the changes. No other
nutritional deficiencies were found. Vitamin E levels were normal in two of three
patients. One patient had no response to treatment with immunosuppressive drugs. The
mechanisms responsible for these neurological complications are poorly understood,
although patients whose duodenal histology fails to improve on a gluten-free diet may be
at greater risk. There have been no real advances in the understanding of this condition
since the original description nearly 30 yr ago.
Celiac disease and type I (insulin-dependent) diabetes mellitus in childhood:
follow-up study.
- Author
Lorini R; Scotta MS; Cortona L; Avanzini MA; Vitali L; De Giacomo C;
Scaramuzza A; Severi F
Address Department of Paediatrics, University of Pavia, Policlinico San Matteo
I.R.C.C.S., Italy.
Source J Diabetes Complications, 1996 May-Jun, 10:3, 154-9
Abstract To ascertain the specificity of IgA and IgG antigliadin (IgA-AGA, IgG-AGA),
IgA-antireticulin (R1-ARA), and antiendomysial (AEA) antibodies for the diagnosis of
celiac disease, we evaluated 133 type I diabetic children aged 1.4-28.4 years (mean 14.1
+/- 6.6), with diabetes from onset to 20.5 years. Fifty-three patients were considered at
onset and 49 of these also during follow-up. IgA-AGA and IgG-AGA were determined by
enzyme-linked immunosorbent assay (ELISA), R1-ARA and AEA by indirect immunofluorescence.
IgA-AGA were positive in 20 of 133 (15%), IgG-AGA were positive in seven of 133 (5.26%),
while R1-ARA and AEA were positive in three patients. At the onset of disease we found
elevated IgA-AGA in 17 of 53 (32%) patients, IgG-AGA in four (7.55%) patients, three of
them with IgA-AGA as well; R1-ARA and AEA were present in three (5.66%) patients, all with
high IgA-AGA levels. During 1-10 year follow-up IgA-AGA decreased to within the normal
range in 13 patients, with elevated IgA-AGA at onset but without R1-ARA and AEA; in four
patients with high IgA-AGA at onset, IgA-AGA remained constantly elevated as did R1-ARA
and AEA in three of them; and two patients, without IgA-AGA, R1-ARA, and AEA at onset,
became positive for all three antibodies. Intestinal biopsy confirmed a diagnosis of
celiac disease in five of these with IgA-AGA, R1-ARA, and AEA, but not in one patient with
persistent IgA-AGA but no AEA and R1-ARA, suggesting that R1-ARA and AEA are more reliable
markers for the screening of celiac disease in type I diabetic patients.
Clinical aspects of coeliac disease in children with insulin-dependent diabetes
mellitus.
- Author
Lorini R; Scaramuzza A; Vitali L; d'Annunzio G; Avanzini MA; De Giacomo C;
Severi F
Address Department of Pediatrics, University of Pavia, Italy.
Source J Pediatr Endocrinol Metab, 1996 Mar, 9 Suppl 1:, 101-11
Abstract Coeliac disease (CD) is heterogeneous in its clinical presentation and
pathological expression. Silent, latent and potential forms represent the submerged part
of the so-called "coeliac iceberg". The association of insulin-dependent
diabetes mellitus (IDDM) and CD has been widely reported. For the screening of CD in
diabetic patients, anti-reticulin R1 (ARA-R1) and anti-endomysium (AEA) antibodies are
more reliable markers than anti-gliadin (AGA) antibodies. Recent studies have reported an
increased prevalence of CD in children with IDDM. In our experience intestinal biopsy
confirmed a diagnosis of CD in 6 out of 172 diabetic patients, with a prevalence of 3.5%.
Only occasionally does CD precede the onset of IDDM; more often CD is diagnosed shortly or
sometimes years after the onset of diabetes. Typical gastrointestinal complaints of CD
(such as diarrhoea, abdominal distension) are rare in IDDM patients, while atypical
isolated signs or symptoms of CD are more common, in particular sideropenic anemia, short
stature, delayed puberty, epilepsy, hypertransaminasemia, dyspeptic symptoms, herpetiform
dermatitis, and recurrent aphthous stomatitis. It is recommended that all diabetic
children, even those asymptomatic, should be screened yearly for CD, using a combination
of AGA plus ARA-R1 and AEA.
Gluten-sensitive enteropathy in patients with insulin-dependent diabetes mellitus.
- Author
Rensch MJ; Merenich JA; Lieberman M; Long BD; Davis DR; McNally PR
Address Fitzsimons Army Medical Center, Aurora, Colorado, USA.
Source Ann Intern Med, 1996 Mar 15, 124:6, 564-7
Abstract OBJECTIVE: To determine the prevalence of celiac disease in a cohort of
patients with insulin-dependent diabetes mellitus and to describe the clinical
characteristics of patients with coexistent disease. DESIGN: Prospective cohort study.
SETTING: U.S. Army medical center. PATIENTS: 47 patients with insulin-dependent diabetes
mellitus. MEASUREMENTS: Antiendomysial antibody testing was used to screen for celiac
disease. The diagnosis of celiac disease required histologic evidence of villous atrophy
and crypt hyperplasia and a positive antiendomysial antibody test result. In patients
identified as having coexistent disease, complete blood counts, multiphasic biochemical
testing, D-xylose absorption testing, and bone mineral density estimates were done.
RESULTS: 3 of 47 patients with insulin-dependent diabetes mellitus (6.4%; 95% CI, 1.4% to
17.5%) had positive antiendomysial antibody test results and small-bowel biopsy specimens
consistent with celiac disease. The 95% CI lies entirely above the estimated prevalence of
celiac disease expected in the general U.S. population, which ranges from 0.02% to 0.1%.
Mean bone mineral densities were 0.8 and 1.1 SD below age-, ethnicity-, and sex-matched
controls in each of the 2 antiendomysial antibody-positive patients tested. Small bowel
absorption was abnormal in 1 of the 2 patients tested by D-xylose. Anemia and
hypoalbuminemia were not detected in any of the patients with coexistent disease. Only 1
of the 3 patients had symptoms of diarrhea. All patients were at or above their ideal body
weights. CONCLUSIONS: Celiac disease appears to be more common among patients with
insulin-dependent diabetes mellitus than in the general U.S. population (p less than
0.001). Two of the three patients with coexistent disease in this study had subclinical or
latent celiac disease.
Polymyositis, arthritis, and proteinuria in a patient with adult celiac disease.
- Author
Evron E; Abarbanel JM; Branski D; Sthoeger ZM
Address Department of Internal Medicine, Kaplan Hospital, Rehovot, Israel.
Source J Rheumatol, 1996 Apr, 23:4, 782-3
Abstract A 37-year-old woman developed polymyositis and arthritis concomitantly with
proteinuria and watery diarrhea. Repeated duodenal biopsies and serological evaluation
established the diagnosis of adult celiac disease. Treatment with gluten-free diet
resolved all clinical and laboratory abnormalities.
The arthritis of coeliac disease: prevalence and pattern in 200 adult patients.
- Author
Lubrano E; Ciacci C; Ames PR; Mazzacca G; Oriente P; Scarpa R
Address Rheumatology Unit, Federico II University, Naples, Italy.
Source Br J Rheumatol, 1996 Dec, 35:12, 1314-8
Abstract Arthritis has often been alluded to as an extra-intestinal clinical
manifestation of coeliac disease, but definitive data regarding its prevalence are still
lacking. We therefore evaluated the overall prevalence of articular involvement in 200
consecutive adult coeliac patients attending routine gastroenterology follow-up and in 40
controls, and determined whether the prevalence and pattern of articular involvement
varied according to the dietary status. An arthritis was present in 26% of patients and in
7.5% of controls, prevalences ranging from 41% in patients on a regular diet to 21.6% in
patients on a gluten-free diet (P < 0.005). Arthritis was peripheral in 19 patients,
axial in 15 and an overlap of both in 18 subjects. These data suggest that arthritis is
much more common than previous reports have indicated, particularly in patients receiving
an appropriate dietary regimen, and support the need for combined gastrointestinal and
rheumatological follow-up in coeliac patients.
Prevalence of celiac disease in patients with juvenile chronic arthritis.
- Author
Lepore L; Martelossi S; Pennesi M; Falcini F; Ermini ML; Ferrari R;
Perticarari S; Presani G; Lucchesi A; Lapini M; Ventura; A
Address The Clinica Pediatrica and the Laboratorio di Immunologia, Istituto
perl'Iinfanzia di Trieste, Italy.
Source J Pediatr, 1996 Aug, 129:2, 311-3
Abstract We estimated the prevalence of celiac disease in children with juvenile
chronic arthritis (JCA), using antiendomysium antibodies as the screening test to select
patients for intestinal biopsy. We studied 119 children with JCA and found four patients
with antiendomysium antibodies. In three of these patients (2.5%), intestinal biopsy
revealed villous atrophy; in the fourth the intestinal mucosa was normal. We conclude that
the prevalence of celiac disease is increased in patients with JCA.
Adult celiac disease is frequently associated with sacroiliitis.
- Author
Usai P; Boi MF; Piga M; Cacace E; Lai MA; Beccaris A; Piras E; La Nasa G;
Mulargia M; Balestrieri A
Address Istituto di Medicina Interna, University of Cagliari, Italy.
Source Dig Dis Sci, 1995 Sep, 40:9, 1906-8
Abstract No data are available on the presence and frequency of peripheral or
central joint disease, routinely determined by bone scintigraphy with 740 MBq of
[99mTc]MDP, in adult celiac disease. Bone scintigraphy was carried out to detect early
acute inflammatory lesions in 22 adult celiac patients (15 females and seven males; mean
age 36.72 years, range 17-63). Bone scintigraphy was positive for sacroiliitis in 14 cases
(63.6%). Except in the case of one patient suffering from rheumatoid arthritis, laboratory
data were normal. Our data suggest that as in other chronic intestinal diseases, celiac
disease in adults, is frequently associated with central joint disease. This high
incidence of sacroiliitis, the joint disease most frequently found in our patients, has
not been previously reported in other series. We believe, therefore, this difference could
be explained by the different methodology used for the screening of joint disease.
Pancreatic enzyme therapy in childhood celiac disease. A double-blind prospective
randomized study.
- Author
Carroccio A; Iacono G; Montalto G; Cavataio F; Lorello D; Greco L; Soresi M;
Notarbartolo A
Address Cattedra di Medicina Interna, UniversitÄa di Palermo, Italy.
Source Dig Dis Sci, 1995 Dec, 40:12, 2555-60
Abstract The validity of pancreatic enzyme substitution therapy in the two months
following diagnosis of celiac disease was investigated. Twenty patients (8 males, 12
females), mean age 14.2 months (group A) received an enzyme substitution preparation. The
control group (group B) included 20 patients (9 males, 11 females), mean age 14.5 months,
treated with placebo. Before starting treatment, we performed a stratification for age,
weight-for-age at diagnosis, and degree of pancreatic insufficiency. The therapies were
then administered randomly in double-blind fashion. On diagnosis and 30 and 60 days after
commencement of a gluten-free diet with identical calorie intake in both groups, a series
of anthropometric variables were determined. After 30 days weight increase in group A
patients was significantly higher (in grams) than in group B: 1131 +/- 461 vs 732 +/- 399
(P < 0.006). Weight-for-age increase also was greater in group A than in group B: 9.2
+/- 5.1% vs 5.0 +/- 4.0% (P < 0.002). The increase in height Z score,
weight-for-height, arm circumference, and subscapular and tricipital fold measurements
were greater in group A patients than those in group B, but the difference was not
significant. After 60 days of therapy none of the parameters considered were significantly
different in the two groups. We concluded that pancreatic enzyme therapy is certainly
useful in the first 30 days after diagnosis of celiac disease.
Celiac disease and alopecia areata: report of a new association.
- Author
Corazza GR; Andreani ML; Venturo N; Bernardi M; Tosti A; Gasbarrini G
Address Department of Internal Medicine, University of L'Aquila, Italy.
Source Gastroenterology, 1995 Oct, 109:4, 1333-7
Abstract Celiac disease is frequently associated with other autoimmune disorders but
has never been reported in association with alopecia areata. In a routine clinical
practice, 3 patients with such an association were observed. In one of the patients,
celiac disease was diagnosed after the occurrence of malabsorption symptoms. In the
youngest patient, a 14-year-old boy, gluten-free diet resulted in complete regrowth of
scalp and body hair. A prospective screening program for celiac disease using antigliadin
and antiendomysial antibodies was therefore set up in 256 consecutive outpatients with
alopecia areata. Three patients, all completely asymptomatic for intestinal diseases, were
found to be positive and underwent biopsy. Histological analysis showed a flat intestinal
mucosa consistent with the diagnosis of celiac disease. The results show that alopecia
areata may constitute the only clinical manifestation of celiac disease and that the
association between these two conditions is a real one because the observed frequency of
association is much greater than can be expected by chance. It is suggested that
antigliadin and antiendomysial antibodies should be included in the work-up of patients
with alopecia areata.
Increased proinflammatory cytokine gene expression in the colonic mucosa of coeliac
disease patients in the early period after gluten challenge.
- Author
Chowers Y; Marsh MN; De Grandpre L; Nyberg A; Theofilopoulos AN; Kagnoff MF
Address Department of Medicine, University of California, San Diego, La Jolla
92093-0623, USA.
Source Clin Exp Immunol, 1997 Jan, 107:1, 141-7
Abstract Activation of T cells in the intestinal mucosa in response to gluten
exposure is thought to play a key role in the pathogenesis of coeliac disease. Moreover,
the response of the rectal mucosa to gluten challenge has been considered a useful
predictor of gluten sensitivity in coeliac disease. In the present study, we assessed
early changes in the expression of proinflammatory cytokine genes and the T cell receptor
(TCR) Vbeta repertoire in the rectal mucosa of coeliac disease patients following
experimental gluten challenge. Cytokine gene expression was assessed in rectal mucosal
biopsies from coeliac disease subjects and controls before and after rectal gluten
challenge using quantitative reverse transcription polymerase chain reaction analysis, and
the TCR Vbeta repertoire was characterized using a multiprobe RNase protection assay.
Marked up-regulation of expression of the C-X-C chemokine IL-8, the proinflammatory
cytokine IL-1beta, and the C-C chemokine monocyte chemotactic protein-1 occurred within 24
h of rectal gluten challenge in coeliac disease subjects, but not in controls.
Furthermore, these changes occurred in the absence of parallel changes in the expressed
repertoire of TCR Vbeta genes in the rectal mucosa. Thus, an increased expression of
proinflammatory cytokine genes precedes the expansion of antigen-specific T cell
populations in the early period following experimental exposure of the rectal mucosa of
coeliac disease patients to gluten. These findings provide new insights into pathways that
may be involved in the activation or reactivation of coeliac disease.
Infertility and coeliac disease.
- Author
Collin P; Vilska S; Heinonen PK; HÂallstrÂom O; Pikkarainen P
Address Department of Medicine, University of Tampere, Finland.
Source Gut, 1996 Sep, 39:3, 382-4
Abstract BACKGROUND: Coeliac women may suffer from gynaecological and obstetric
complications. It is possible that these complications are the first symptom of coeliac
disease. AIMS: To investigate the occurrence of subclinical coeliac disease in patients
with infertility or recurrent miscarriages. SUBJECTS: Women of reproductive age who were
attending the hospital because of either primary or secondary infertility, or two or more
miscarriages. Women undergoing sterilisation served as control subjects. METHODS: The
diagnostic investigation for infertility included the endocrine status, diagnostic
laparoscopy, investigation of tubal patency, postcoital test, and semen analysis of the
partner. Circulating antibodies against IgA class reticulin and gliadin were used in
screening for coeliac disease. In positive cases, the diagnosis was confirmed by small
bowel biopsy specimens. RESULTS: Four (2.7%) of 150 women in the infertility group, and
none of the 150 control subjects were found to have coeliac disease (p = 0.06). All four
women with coeliac disease suffered from infertility of unexplained origin. Altogether 98
women had no discoverable reason for infertility. Thus, in this subgroup the frequency of
coeliac disease was 4.1% (four of 98), the difference from the control group being
statistically significant (p = 0.02). None of the coeliac women had extensive
malabsorption, but two had iron deficiency anaemia. One women with coeliac disease has had
a normal delivery. None of the 50 women with miscarriage had coeliac disease. CONCLUSION:
Patients having fertility problems may have subclinical coeliac disease, which can be
detected by serological screening tests. Silent coeliac disease should be considered in
the case of women with unexplained infertility.
Incidence of familial dermatitis herpetiformis.
- Author
Reunala T
Address Department of Dermatology, University of Helsinki, Finland.
Source Br J Dermatol, 1996 Mar, 134:3, 394-8
Abstract Dermatitis herpetiformis (DH) and coeliac disease (CD) are gluten-sensitive
diseases which have a common immunogenetic background, with the histocompatibility locus
antigen (HLA) alleles DQ A1*0501 and B1*0201 in the short arm of chromosome 6. CD is well
known to cluster in families whereas DH has not been generally regarded as a familial
disease. To study the familial incidence of DH, a prospective study was started in 1969 at
the Department of Dermatology of Helsinki University Hospital and in 1976 at the
Department of Dermatology of Tampere University Hospital. A total of 1018 patients with DH
were diagnosed and questioned for positive family histories. Of the 999 unrelated DH
patients, 105 (10.5%) had one or several affected first-degree relatives. The disease in
the relatives was either DH (4.4%) or CD (6.1%). Analysis of the 105 families showed that
13.6% of parents, 18.7% of siblings and 14.0% of children were affected, a segregation
pattern which fits well to a dominant mode of Mendelian inheritance. Gender may also be
important because the first-degree relatives affected with DH were more often females and
those affected with CD twice as often females as males. In contrast, there were more males
among the 105 propositi with DH and also among the 894 DH patients with no affected
relatives. The present study clearly shows that DH is a familial disease in which the
first-degree relatives can be affected both with DH and CD, presumably because of a common
genetic background. The environmental factors which could cause the rather high penetrance
of DH and CD in the first-degree relatives of DH patients remain unknown.
Celiac Disease, Gluten & Cancer
Malignancy and survival in dermatitis herpetiformis: a comparison with coeliac disease .
- Author
Collin P; Pukkala E; Reunala T
Address Medical School, University of Tampere, Finland.
Source Gut, 1996 Apr, 38:4, 528-30
Abstract BACKGROUND--Dermatitis herpetiformis is a lifelong, gluten sensitive skin
disease. Patients with dermatitis herpetiformis, similar to patients with coeliac disease
not adhering to a gluten free diet, seem to have increased risk for lymphoma. AIMS--This
study looked at the occurrence of malignancy and survival of patients with dermatitis
herpetiformis and compared the results with those seen in patients with coeliac disease or
in the general population. PATIENTS--A total of 305 adult patients with dermatitis
herpetiformis diagnosed at the University Hospital of Tampere in 1970-1992 were studied.
Most patients started a gluten free diet and at the end of the study 93% of the patients
were adhering to the diet. A control group comprised 383 adult patients with coeliac
disease, 81% of them adhered to a gluten free diet, 6% had a normal diet, and in 13% the
diet history remained unknown. METHODS--The occurrence of malignant diseases and survival
of the patients were assessed up to the end of 1993. Standardised incidence ratios (SIR)
with 95% confidence intervals were used for the malignant diseases. The survival of the
patients was compared with that of the general population. RESULTS--Thirteen (4.3%)
patients with dermatitis herpetiformis developed 14 malignant disorders during the follow
up (SIR 1.25; 95% confidence intervals 0.68 to 2.09). A non-Hodgkin's lymphoma occurred in
four patients with dermatitis herpetiformis, significantly more than expected (SIR 10.3;
2.8-26.3). Thirteen (4.3%) patients with dermatitis herpetiformis died during the follow
up but there was no increased general mortality. In coeliac disease, 13 (3.4%) patients
developed malignancy (SIR 1.16; 0.62 to 1.97), 31 (8.1%) patients died but the survival
rate did not differ from that in the general population. CONCLUSIONS--The incidence of
non-Hodgkin's lymphoma was significantly increased in patients with dermatitis
herpetiformis. The results also confirm that the patients with dermatitis herpetiformis
treated mainly with a gluten free diet have no increased general mortality.
Primary T cell CD30-positive anaplastic large-cell lymphoma associated with
adult-onset celiac disease and presenting with skin lesions.
- Author
Mantovani G; Esu S; Astara G; Lampis B; MacciÄo A; Usai P; Santa Cruz G;
Mura E; Ferreli A
Address Department of Medical Oncology, University of Cagliari, Italy.
Source Acta Haematol, 1995, 94:1, 48-51
Abstract We report the case of a 52-year-old woman with primary CD30+ anaplastic
large-cell lymphoma of T cell phenotype with skin involvement, stage IVB, fulfilling
almost all the clinical, histopathologic and immunophenotypic criteria for this disease,
associated with adult-onset celiac disease. The diagnoses of malignancy and celiac disease
were made during the same clinical episode. The clinical course of the patient has been
extremely favorable and she is in complete remission, 15 months after finishing
consolidation therapy.
Genetics
HLA genotypes and the increased incidence of coeliac disease in Sweden.
- Author
Ploski R; Ascher H; Sollid LM
Address Institute of Transplantation Immunology, National Hospital, University of
Oslo, Norway.
Source Scand J Gastroenterol, 1996 Nov, 31:11, 1092-7
Abstract BACKGROUND: A strong increase of childhood coeliac disease (CD) was found
in Sweden concurrently with changes in the infant feeding pattern. We investigated whether
this increase reflects a recruitment of individuals with less predisposing HLA genotypes.
METHODS: Genomic HLA-DRB1, -DQA1, and -DQB1 typing was performed in 135 Swedish patients
(48 belonging to a low- and 81 to a high-incidence cohort) and 179 controls. The
distribution of HLA class-II genotypes in the cohorts was compared. RESULTS: DQA1*0501 and
DQB1*02 conferred increased risk for CD, and a gene dosage effect of DQB1*02 was found.
The distribution of HLA genotypes among the cohorts did not differ. CONCLUSIONS: The
results suggest that Swedish CD patients do not differ in genetic susceptibility compared
with other populations. No evidence was found suggesting that the increase would be a
result of more frequent development of disease in individuals carrying less predisposing
HLA genotypes.
Immune Mechanisms
Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with
Th1 or Th0 profile dominated by interferon gamma.
- Author
Nilsen EM; Lundin KE; KrajÅci P; Scott H; Sollid LM; Brandtzaeg P
Address Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute
of Pathology, Oslo, Norway.
Source Gut, 1995 Dec, 37:6, 766-76
Abstract Coeliac disease is precipitated in susceptible subjects by ingestion of
wheat gluten or gluten related prolamins from some other cereals. The disease is strongly
associated with certain HLA-DQ heterodimers, for example, DQ2 (DQ alpha 1*0501, beta
1*0201) in most patients and apparently DQ8 (DQ alpha 1*0301, beta 1*0302) in a small
subset. Gluten specific T cell clones (TCC) from coeliac intestinal lesions were recently
established and found to be mainly restricted by HLA-DQ2 or HLA-DQ8. Antigen induced
production of cytokines was studied in 15 TCC from three patients, 10 being DQ2 and five
DQ8 restricted. Cell culture supernatants were prepared by stimulation with gluten
peptides in the presence of DQ2+ or DQ8+ Epstein-Barr virus transformed B cells as antigen
presenting cells (APC). Supernatants were analysed for cytokines by bioassays, ELISA, and
CELISA. Cellular cytokine mRNA was analysed semi-quantitatively by slot blotting and
polymerase chain reaction (PCR). All TCC were found to secrete interferon (IFN) gamma,
often at high concentrations ( 2000 U/ml); some secreted in addition interleukin (IL) 4,
IL 5, IL 6, IL 10, tumour necrosis factor (TNF), and transforming growth factor (TGF)
beta. The last TCC thus displayed a Th0-like cytokine pattern. However, other TCC produced
IFN gamma and TNF but no IL 4, or IL 5, compatible with a Th1-like pattern. In conclusion,
most DQ8 restricted TCC seemed to fit with a Th0 profile whereas the DQ2 restricted TCC
secreted cytokines more compatible with a Th1 pattern. The TCC supernatants induced
upregulation of HLA-DR and secretory component (poly-Ig receptor) in the colonic
adenocarcinoma cell line HT-29.E10, most probably reflecting mainly the high IFN gamma
concentrations. This cytokine, particularly in combination with TNF alpha, might be
involved in several pathological features of the coeliac lesion. The characterised
cytokine profiles thus support the notion that mucosal T cells activated in situ by gluten
in a DQ restricted fashion play a central part in the pathogenesis of coeliac disease.
The gluten-host interaction.
- Author
Tighe MR; Ciclitira PJ
Address Division of Pharmacology, United Medical and Dental Schools of Guy's
Hospital, London, UK.
Source Baillieres Clin Gastroenterol, 1995 Jun, 9:2, 211-30
Abstract Work continues to progress in the unravelling of the molecular interactions
involved in the pathogenesis of coeliac disease. The immunogenetics of the disease
implicate certain HLA DQ alleles as necessary for subsequent disease development. These
HLA molecules have been shown to be necessary in the binding and presentation of gliadin
peptides to antigen-specific T cells. Current work is examining the precise HLA-antigen
interaction that may lead to the development of antigen-blocking agents. The isolation of
antigen-specific T cells has led to the confirmation of a toxic T-cell epitope of the
gliadin protein (residues 31-49) and it would appear likely that additional toxic epitopes
may be similarly characterized in the near future. No common TCR motifs have so far been
detected, although these may become apparent as this work progresses. The gliadin peptide
sequence, residues 31-49, has now been demonstrated to be toxic in vivo. Additional toxic
T-cell epitopes may also be present within gliadins, but this identification of a toxic
gliadin sequence for the first time raises the possibility of future manipulation of the
wheat genome (and other toxic cereals) that could lead to the development of new graminae
cereals with the properties of wheat, but which do not induce toxicity in patients with
coeliac disease.
Gliadin-specific T cell responses in peripheral blood of healthy individuals involve T
cells restricted by the coeliac disease associated DQ2 heterodimer.
- Author
Jensen K; Sollid LM; Scott H; Paulsen G; Kett K; Thorsby E; Lundin KE
Address Institute of Transplantation Immunology, University of Oslo, Norway.
Source Scand J Immunol, 1995 Jul, 42:1, 166-70
Abstract Coeliac disease (CD) is probably caused by an abnormal immune response
towards wheat gliadin in the small intestine. We found that gliadin-specific T cells from
the small intestinal mucosa of HLA-DQ2 positive CD patients were almost exclusively
restricted by the disease-associated DQ2 molecule. In the peripheral blood of CD patients,
a large proportion of gliadin-specific T cells were found to be restricted by DQ
molecules, including DQ2, but many were instead restricted by DR or DP molecules of the
patient. We have now investigated gliadin-specific T cell responses in peripheral blood
from healthy individuals. Four of 20 persons tested had strong in vitro responses and were
used as donors for gliadin-specific T cell clones. We found gliadin-specific T cells
restricted by the CD-associated DQ2 molecule in peripheral blood for two of these four
individuals. It is the presence of such T cells also in the small intestinal mucosa which
seems typical of CD.
Role of T cell receptor delta gene in susceptibility to celiac disease.
- Author
Roschmann E; Wienker TF; Volk BA
Address Department of Internal Medicine, Division of Gastroenterology, University of
Freiburg, Germany.
Source J Mol Med, 1996 Feb, 74:2, 93-8
Abstract There is a strong genetic influence on the susceptibility to celiac
disease. Although in the vast majority of patients with celiac disease, the
HLA-DQ(alpha1*0501, beta1*0201) heterodimer encoded by the alleles HLA-DQA1*0501 and
HLA-DQB1*0201 seems to confer the primary disease susceptibility, it cannot be excluded
that other genes contribute to disease susceptibility, as indicated by the difference in
concordance rates between monozygotic twins and HLA identical siblings (70% vs. 30%).
Obviously other genes involved in the genetic control of T cell mediated immune response
could potentially influence susceptibility to celiac disease. The density of T cells using
the gammadelta T cell receptor (TCR) is considerably increased in the jejunal epithelium
of patients with celiac disease, an abnormality considered to be specific for celiac
disease. This suggests an involvement of gammadelta T cells in the pathogenesis of the
disease. To ascertain whether the TCR delta (TCRD) gene contributes to celiac disease
susceptibility we carried out an association study and genetic linkage analysis using a
highly polymorphic microsatellite marker at the TCRD locus on chromosome 14q11.2. The
association study demonstrated no significant difference in allele frequencies of the TCRD
gene marker between celiac disease patients and controls; accordingly, the relative risk
estimates did not reach the level of statistical significance. In the linkage analysis,
performed in 23 families, the logarithm of the odds (LOD) scores calculated for celiac
disease versus the TCRD gene marker excluded linkage, suggesting that there is no
determinant contributing to celiac disease status at or 5 cM distant to the analyzed TCRD
gene marker. In conclusion, the results of the present study provide no evidence that the
analyzed TCRD gene contributes substantially to celiac disease susceptibility.
Epithelial cell proliferation in childhood enteropathies.
- Author
Savidge TC; Shmakov AN; Walker-Smith JA; Phillips AD
Address Academic Department of Paediatric Gastroenterology, Queen Elizabeth Hospital
for Children, London.
Source Gut, 1996 Aug, 39:2, 185-93
Abstract BACKGROUND/AIM: The aim of this study was to investigate epithelial cell
turnover in childhood enteropathy to establish whether common disease related mechanisms
operate. Levels of epithelial cell proliferation were measured in children with food
intolerance (cows' milk protein intolerance and coeliac disease), and after infection with
Giardia lamblia, Cryptosporidium, and enteropathogenic Escherichia coli. METHODS:
Comparative measures of epithelial cell proliferation were performed by recording mitotic
activity and MIB-1 immunoreactivity in proximal small intestinal biopsy specimens.
RESULTS/CONCLUSIONS: A hyperplastic crypt response was evident in all of the disease
states examined and was particularly pronounced in coeliac disease and in infection with
enteropathogenic E coli, where mitotic and MIB-1 labelling indices were significantly
raised above control values. In contrast with coeliac disease, increased crypt cell
production rates in enteropathogenic E coli infection were also due to an expansion of the
crypt proliferation compartment, without a comparable increase in crypt cell numbers.
Crypt hyperplasia is therefore a common tissue response to mucosal damage in food allergy
and infection, although disease specific mechanisms are evident.
Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV
and their relation to diarrhoea.
- Author
Keating J; Bjarnason I; Somasundaram S; Macpherson A; Francis N; Price AB;
Sharpstone D; Smithson J; Menzies IS; Gazzard; BG
Address Department of Medicine, Chelsea and Westminster Hospital, London.
Source Gut, 1995 Nov, 37:5, 623-9
Abstract Intestinal function is poorly defined in patients with HIV infection.
Absorptive capacity and intestinal permeability were assessed using 3-O-methyl-D-glucose,
D-xylose, L-rhamnose, and lactulose in 88 HIV infected patients and the findings were
correlated with the degree of immunosuppression (CD4 counts), diarrhoea, wasting,
intestinal pathogen status, and histomorphometric analysis of jejunal biopsy samples.
Malabsorption of 3-O-methyl-D-glucose and D-xylose was prevalent in all groups of patients
with AIDS but not in asymptomatic, well patients with HIV. Malabsorption correlated
significantly (r = 0.34-0.56, p < 0.005) with the degree of immune suppression and with
body mass index. Increased intestinal permeability was found in all subgroups of patients.
The changes in absorption-permeability were of comparable severity to those found in
patients with untreated coeliac disease. Jejunal histology, however, showed only mild
changes in the villus height/crypt depth ratio as compared with subtotal villus atrophy in
coeliac disease. Malabsorption and increased intestinal permeability are common in AIDS
patients. Malabsorption, which has nutritional implications, relates more to immune
suppression than jejunal morphological changes.
Endomysial antibodies as unreliable markers for slight dietary transgressions in
adolescents with celiac disease.
- Author
Troncone R; Mayer M; Spagnuolo F; Maiuri L; Greco L
Address Department of Pediatrics, University Federico II, Naples, Italy.
Source J Pediatr Gastroenterol Nutr, 1995 Jul, 21:1, 69-72
Abstract Adolescents with celiac disease often fail to adhere to a strict
gluten-free diet. The value of endomysial antibodies in assessing the dietary compliance
of such adolescents has been assessed in 23 patients divided into four groups according to
their daily gluten intake. Serum endomysial antibodies were absent in all subjects on a
gluten-free diet and consistently present in those ingesting 2 g/day of gluten. Only one
of six and three of six teenagers with celiac disease with an intake of < 0.5 and 0.5-2
g/day, respectively, had endomysial antibodies in their serum, despite the presence in
three of six and five of six of significant changes in the mucosal architecture, as shown
by computerized morphometry of jejunal biopsies. In conclusion, endomysial antibodies
cannot be considered a valid marker for slight dietary transgressions.
Leukotriene B4 and C4 metabolism in small intestine mucosa of children with celiac
disease.
- Author
Shimizu T; Beijer E; Strandvik B
Address Department of Pediatrics, Juntendo University, Tokyo, Japan.
Source J Pediatr Gastroenterol Nutr, 1995 Nov, 21:4, 426-9
Abstract The enhanced generation of eicosanoids, including leukotrienes (LTs), may
be involved in the pathophysiology of small intestine mucosal injury in patients with
celiac disease. We investigated the metabolism of LTB4 and LTC4 by small intestine mucosa
in patients with celiac disease by incubating biopsies of small intestine mucosa from
patients and healthy subjects in media containing LTB4 and LTC4 and measuring the changes
in LTB4 and cysteinyl LT concentrations in the incubation media. There was no significant
degradation of LTB4 during a 60-min incubation of the small intestine mucosa from either
children with celiac disease or controls. LTC4 was metabolized to LTD4 and LTE4 in a
time-dependent manner by the small intestine mucosa of both patients and controls.
However, the decreases in LTC4 and the increases in LTD4 and LTE4 by the intestinal mucosa
from patients with celiac disease occurred more slowly than the changes observed in
control experiments. Reduced catabolism of LTC4 in the small intestine mucosa due to
villous atrophy may contribute to increased levels of LTC4 and may play an important role
in the pathophysiology of celiac disease.
Evidence that intestinal intraepithelial lymphocytes are activated cytotoxic T cells
in celiac disease but not in giardiasis.
- Author
Oberhuber G; Vogelsang H; Stolte M; Muthenthaler S; Kummer AJ; Radaszkiewicz
T
Address Department of Clinical Pathology, University of Vienna Medical School,
Austria.
Source Am J Pathol, 1996 May, 148:5, 1351-7
Abstract To further define intraepithelial lymphocytes (IELs) in celiac disease (CD)
and giardiasis, IELs were probed for the presence of cytolytic granules containing
granzyme B (GrB) and T-cell-restricted intracellular antigen (TIA)-1. The expression of
TIA-1, GrB, CD3 (T-cell-receptor-associated complex), and Leu-7 (subset of natural killer
cells) was studied by a sensitive three-step immunoperoxidase technique. Stained IELs were
determined quantitatively, and results were expressed as number of stained IELs per 100
epithelial cells (ECs). The relative content in labeled lamina propria lymphocytes was
determined and expressed as the percentage of all lamina propria cells counted. When
compared with controls, CD3+ and GrB+ IELs were significantly increased (P < 0.0004) in
CD paralleled by an increase in TIA-1+ IELs (P < 0.0004). In CD, the highest numbers of
IELs containing GrB were found in subjects with a flat mucosa (median, 38 IELs/100 ECs, P
< 0.0004), followed by cases with shortened and blunted villi (median, 8 IELs/100 ECs,
P < 0.0004) and, finally, CD patients with an intact villous architecture (median, 0.5
IELs/100 ECs, P < 0.02). Except for cases with giardiasis, Leu-7+ IELs were virtually
absent in all groups as were GrB+ IELs in the controls and in subjects with giardiasis. In
the lamina propria of CD subjects, GrB+ lymphocytes were also significantly increased (P
< 0.001), whereas controls and cases with giardiasis were essentially free of GrB+
cytotoxic T lymphocytes. The percentage of CD3+ lamina propria lymphocytes was nearly
equal in all groups. In humans and mice, extensive studies revealed a GrB expression to be
absolutely restricted to activated cytotoxic T lymphocytes and natural killer cells.
TIA-1, on the other hand, is considered a marker of resting T lymphocytes possessing
cytolytic potential. We therefore conclude that IELs are cytotoxic T cells that are in a
resting state in the normal small bowel and in giardiasis. In CD, they become activated as
suggested by the GrB positivity of their granules.
In vitro mucosal digestion of synthetic gliadin-derived peptides in celiac disease.
- Author
Cornell HJ; Rivett DE
Address Department of Applied Chemistry, Royal Melbourne Institute of Technology,
Australia.
Source J Protein Chem, 1995 Jul, 14:5, 335-9
Abstract Two celiac-active synthetic peptides derived from the A-gliadin structure
corresponding to residues 8-19 (LQPQNPSQQQPQ) and to 11-19 were digested in vitro with
small intestinal mucosa from children with celiac disease in remission and from normal
children. The products of digestion were separated into two fractions on the basis of M(r)
<400 and M(r) 400 by gel permeation chromatography and subjected to amino acid
analysis. After digestion of the dodecapeptide with celiac mucosa, 71 +/- 14% (molar) of
the total digestion products remained in the M(r) 400 fraction. Glutamine, proline,
serine, and asparagine were the major amino acids present. Glutamine, proline, and leucine
were the major amino acids in the M(r) <400 fraction. The M(r) 400 fraction from the
celiac mucosal digestion of the nonapeptide was of similar composition to the
corresponding fraction from the dodecapeptide and represented 78 +/- 15% of the total
products. Digestion of the two peptides with normal mucosa gave lower amounts of products
in the M(r) 400 fraction, but they were of similar composition to the corresponding
fractions from the celiac mucosal digestion. Peptides such as NPSQQP and QNPSQQQ may be
present in the M(r) 400 fractions since glutamine and proline are present in the
approximate ratio of 2:1, respectively. The results indicate a defect in the mucosal
digestion of peptides which are active in an animal model of celiac disease.
Clinical, pathological, and antibody pattern of latent celiac disease: report of three
adult cases.
- Author Corazza GR; Andreani ML; Biagi F; Bonvicini F; Bernardi M; Gasbarrini G
- Address
Dipartimento di Medicina Interna dell'UniversitÄa dell'Aquila, Italy.
- Source
Am J Gastroenterol, 1996 Oct, 91:10, 2203-7
- Abstract
We report the clinical, pathological, and serological findings of three
adult patients with latent celiac disease. The initial intestinal biopsies, which were
normal, were carried out in the first case during an upper gastrointestinal endoscopy
performed for a duodenal ulcer, in the second case for first-degree familiarity with a
celiac patient, and in the third case because of the presence of malabsorption symptoms.
In all three cases, intraepithelial lymphocytes were within the normal range in the first
biopsy and cannot, therefore, be considered as a marker of latent celiac disease. In only
two of the three patients was it possible to carry out the search for the serum antibodies
connected with celiac disease at the time of the first biopsy. In both these cases, the
antijejunal antibodies were present before the development of the intestinal lesions.
HLA-DRB, -DQA, and -DQB polymorphism in celiac disease and enteropathy-associated
T-cell lymphoma. Common features and additional risk factors for malignancy.
- Author
Howell WM; Leung ST; Jones DB; Nakshabendi I; Hall MA; Lanchbury JS;
Ciclitira PJ; Wright DH
Address Molecular Immunology Group, Tenovus Laboratory, Southampton General
Hospital, United Kingdom.
Source Hum Immunol, 1995 May, 43:1, 29-37
Abstract CD is a gluten-sensitive enteropathy, strongly associated with expression
of the DQA1*0501, DQB1*0201 genotype. CD patients have an increased risk of malignancy,
particularly EATCL. However, it is controversial as to whether adults with EATCL represent
a subgroup of patients with CD or should be regarded as a distinct entity. To investigate
the genetic relationship between CD and EATCL, HLA class II DRB1, DQA1, and DQB1 typing of
peripheral blood, frozen or paraffin-embedded biopsy tissue obtained from Caucasian
patients with CD (n = 91) or EATCL (n = 47) was performed by PCR-SSOP typing. Genotype
frequencies were compared with those observed in 151 unrelated control individuals. A
total of 83 (91%) of 91 CD patients were of DQA1*0501, DQB1*0201 genotype (pc < 10(-6),
RR = 522.2), compared with 40 (93%) of 43 EATCL patients (pc < 10(-6), RR = 44.2) with
amplifiable DNA versus 35 (23%) of 151 controls. DRB1*03 frequencies were also elevated in
both patient groups (79 of 91 in CD [87%; pc < 10(-6), RR = 24.5] and 38 of 40 in EATCL
[95%; pc < 10(-6), RR = 70.7]) compared with controls (32 of 151, 21%). These results
confirm previous studies of HLA associations in CD and also suggest that EATCL arises in
individuals with the DQA1*0501, DQB1*0201 CD-predisposing genotype. However, the frequency
of DRB1*03,04 heterozygotes was significantly increased in the EATCL group (16 of 40, 40%)
compared with both control individuals (3 of 151, 2%; pc < 10(-6), RR = 32.9) and
uncomplicated CD patients (6 of 91, 7%; pc = 0.04, RR = 9.4
Repeatability of the sugar-absorption test, using lactulose and mannitol, for measuring
intestinal permeability for sugars.
- Author
van Elburg RM; Uil JJ; Kokke FT; Mulder AM; van de Broek WG; Mulder CJ;
Heymans HS
Address Department of Pediatrics, Beatrix Children's Hospital, University Hospital
of Groningen, The Netherlands.
Source J Pediatr Gastroenterol Nutr, 1995 Feb, 20:2, 184-8
Abstract Differential sugar-absorption tests for measuring intestinal permeability
for sugars have been studied in a variety of gastrointestinal diseases. Their use in
general practice has been hampered by a lack of data on reference values and repeatability
of the test and the laboratory assay. In this study, we determined the reference values of
the sugar-absorption test, using lactulose and mannitol as probe molecules, for children
and adults. The repeatability of the test is good; linear relationship: slope, 0.825 [95%
confidence interval (CI), 0.571, 1.152); intercept, 0.005 (95% CI, -0.004, 0.010). The
repeatability of the laboratory assay for the sugar-absorption test is excellent; linear
relationship: slope, 1.014 (95% CI, 0.870, 1.094); intercept, 0.002 (95% CI, -0.005,
0.010). The validation of the sugar-absorption test makes the test useful as a simple,
noninvasive, reliable intestinal permeability test for sugars, which can be of use for
clinical practice. Taking possible interfering factors into account, the sugar-absorption
test can be used as a diagnostic test for enteropathy of different etiologies and
evaluation of therapeutic interventions in both children and adults. Studies with the
sugar-absorption test may clarify the role of intestinal permeability in the
pathophysiology of a variety of gastrointestinal diseases.
IgA and IgG binding components of wheat, rye, barley and oats recognized by
immunoblotting analysis with sera from adult atopic dermatitis patients.
- Author
Varjonen E; Kalimo K; Savolainen J; Vainio E
Address Department of Dermatology, Helsinki University Central Hospital, Finland.
Source Int Arch Allergy Immunol, 1996 Sep, 111:1, 55-63
Abstract IgA and IgG antibody response of adult atopic dermatitis patients against
neutral/ acidic fractions of wheat, rye, barley and oats was analyzed utilizing an
immunoblotting method. Moreover, the antibody response against ethanol-soluble fraction of
wheat was examined with serum pools of healthy donors, atopic dermatitis patients and
patients with dermatitis herpetiformis or adult celiac disease. All patient sera revealed
polymorphic IgA and IgG binding to cereal peptides with molecular weights of 11-97 kD. The
antibody staining was essentially identical with atopic dermatitis patients and controls.
Patients with dermatitis herpetiformis or celiac disease showed more intensive staining
with the ethanol extract of wheat and showed more IgA-stained bands in immunoblotting. It
seems that the presence of IgA and IgG antibodies to different cereal antigens is a result
of natural exposure and in atopic dermatitis displays little diagnostic significance, in
contrast to antigliadin antibody response in dermatitis herpetiformis and celiac disease.
Measurement of sugar probes in serum: an alternative to urine measurement in intestinal
permeability testing.
- Author
Fleming SC; Duncan A; Russell RI; Laker MF
Address Department of Clinical Biochemistry, University of Newcastle upon Tyne, UK.
Source Clin Chem, 1996 Mar, 42:3, 445-8
Abstract The percentage dose of lactulose and mannitol excreted in urine after oral
ingestion is used as a noninvasive method of assessing small intestinal permeability. The
collection of incomplete or inaccurately timed urine samples can lead to errors in
estimation of sugar probe molecules. We describe an HPLC method for the simultaneous
determination of lactulose and mannitol in serum after oral ingestion of test sugars. We
applied the test to healthy volunteers and to subjects undergoing jejunal biopsy for
suspected gluten-sensitive enteropathy. The ratio of concentrations of lactulose and
mannitol in serum discriminated well between subjects with a normal biopsy and those with
villous atrophy, discrimination being best at 90 min postdose. The results agree well with
lactulose:mannitol ratios determined in urine (r= 0.88), and the two methods can be used
interchangeably. The determination of mannitol and lactulose in serum provides an
acceptable alternative to urine collection and may be particularly useful in young
children. It also reduces the time spent on the investigation from 5 h to 90 min.
Study of the immunohistochemistry and T cell clonality of enteropathy-associated T cell
lymphoma.
- Author
Murray A; Cuevas EC; Jones DB; Wright DH
Address University Department of Pathology, Southampton University Hospitals, United
Kingdom.
Source Am J Pathol, 1995 Feb, 146:2, 509-19
Abstract Specimens from 23 patients with enteropathy-associated T cell lymphoma were
studied by immunohistochemistry after antigen retrieval. Specimens from 14 of these
patients were investigated for the presence of clonal T cell gene rearrangements in both
the tumor and the adjacent enteropathic intestine by the polymerase chain reaction.
Primers for T cell receptor beta and gamma genes were used in a combination that permits
the identification of approximately 90% of T cell receptor rearrangements. Clonal
rearrangements of the T cell receptor were found in 13 of the 14 tumors studied. Specimens
of enteropathic bowel resected with the tumor, but showing no morphological or
immunohistochemical evidence of tumor involvement, showed clonal T cell receptor gene
rearrangements in 11 cases. In 10 of these, the amplified DNA was of the same molecular
weight in the enteropathic bowel as in the corresponding tumor. In 2 cases, sequencing the
polymerase chain reaction product showed identical T cell receptor gene rearrangements in
the tumor and in the adjacent intestine. Uniform staining for p53 was seen in 22 of the 23
tumors. In 9 of 19 cases studied, collections of small lymphocytes in the enteropathic
bowel expressed p53. In all but one of these specimens, a clonal rearrangement of the T
cell receptor genes was identified. We interpret these findings as support for the concept
that enteropathy-associated T cell lymphoma arises on a background of gluten-sensitive
enteropathy with evolution of neoplastic T cell clones from the reactive T cell population
present in the enteropathic bowel.
Celiac disease and hypoparathyroidism: cross-reaction of endomysial antibodies with
parathyroid tissue.
- Author
Kumar V; Valeski JE; Wortsman J
Address IMMCO Diagnostics, Inc., Buffalo, NY 14223, USA.
Source Clin Diagn Lab Immunol, 1996 Mar, 3:2, 143-6
Abstract Celiac disease (CD) is a gluten-sensitive enteropathy characterized by the
presence of serum antibodies to endomysial reticulin and gliadin antigens. CD has been
associated with various autoimmune endocrine disorders, such as diabetes. We report a rare
case of idiopathic hypoparathyroidism with coexistent CD characterized by the presence of
serum autoantibodies. Studies were conducted to determine the specificities of these
autoantibodies and to localize the antibody binding sites by indirect immunofluorescence
and immunoelectron microscopy. Sera from a patient with idiopathic hypoparathyroidism and
CD and from two patients with CD alone were tested by indirect immunofluorescence for
autoantibodies to parathyroid and endomysial antigens. The specificities of the antibody
reactions were determined by testing the sera before and after absorption with monkey
stomach tissue. In addition, immunoelectron microscopic studies were performed to
determine the localization of the endomysial antigen. Indirect-immunofluorescence studies
on the patient's serum were positive with the parathyroid as well as the endomysial
substrate. Similar reactions were also observed with the sera of endomysial
antibody-positive patients with CD. Absorption of the sera with monkey stomach powder,
which is known to have the endomysial antigen, abolished the antibody activities on both
the endomysial substrate and the parathyroid tissue. Immunoelectron microscopic studies
showed that endomysial antibody activity was associated with antigens localized on the
myocyte plasma membrane and in the intercellular spaces. Thus, reactions of the patient's
serum with the parathyroid tissue were due to endomysial antibodies and were not
parathyroid specific as in patients with idiopathic hypoparathyroidism who did not have
coexistent CD. In conclusion, indirect-immunofluorescence tests on parathyroid tissue
detect not only tissue-specific antibodies but also cross-reactive antibodies, and this
should be taken into consideration when these tests are performed.
Molecular mimicry as a possible cause of autoimmune reactions in celiac disease?
Antibodies to gliadin cross-react with epitopes on enterocytes.
- Author
TuÅckovÆa L; TlaskalovÆa-HogenovÆa H; FarrÆe MA; KarskÆa K; Rossmann P;
KolÆinskÆa J; Kocna P
Address Department of Immunology and Gnotobiology, First Faculty of Medicine,
Prague, Czech Republic.
Source Clin Immunol Immunopathol, 1995 Feb, 74:2, 170-6
Abstract Structural similarities between external antigen and self components are
believed to be one of the possible causes of autoimmunity. This study describes the
presence of similar structures shared by gliadin and enterocyte surface molecules
recognized by antigliadin mAbs. The reactivity of mAbs to gliadin was followed by ELISA
using fixed enterocytes, their brush-border membranes, or purified enterocyte antigen. The
specificity of reaction was confirmed by ELISA inhibition studies and by
immunohistochemical staining of rat tissue sections using biotin-avidin-peroxidase
technique. Immunoprecipitation analysis of 125I-labeled intestinal epithelial cells using
antigliadin mAb revealed the presence of two main cross-reactive molecules of 28 and 62
kDa. The 62-kDa and an associated 66-kDa protein were isolated by affinity chromatography.
Immunoblotting analysis showed that a 28-kDa protein detected by immunoprecipitation also
reacted with IgA of celiac disease patient sera.
Enteropathy-associated T-cell lymphoma in the West of Ireland: low-frequency of
Epstein-Barr virus in these tumors.
- Author
Walsh SV; Egan LJ; Connolly CE; Stevens FM; Egan EL; McCarthy CF
Address Department of Histopathology, University College Hospital, Galway, Ireland.
Source Mod Pathol, 1995 Sep, 8:7, 753-7
Abstract The Epstein-Barr virus has been implicated in the etiology of endemic
Burkitt's lymphoma, post-transplant lymphoma, large-cell anaplastic CD30 (Ki-1)-positive
lymphoma, and in many T-cell lymphomas. A recent report has found Epstein-Barr virus
genome in association with 4 of 11 cases (36%) of enteropathy-associated T-cell lymphoma.
In a retrospective study, we have characterized 22 consecutive cases of
enteropathy-associated T-cell lymphoma from the West of Ireland where celiac disease is
endemic. All cases were immunophenotyped with T- and B-cell markers
Identification of major rye secalins as coeliac immunoreactive proteins.
- Author
Rocher A; Calero M; Soriano F; MÆendez E
Address Unidad de AnÆalisis Estructural de ProteÆinas, Centro Nacional de
BiotecnologÆia, Campus Universidad AutÆonoma, Cantoblanco, Madrid, Spain.
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