Influence of cow's milk proteins and gluten on human duodenal mucosa in organ culture

Forty-five duodenal biopsies from 33 children and 3 adult patients were maintained in organ culture for 24 h and exposed to various cow's milk proteins and gluten. In 10 of 11 celiac patients with a flat duodenal mucosa, and in 2 of 4 patients with partial villous atrophy, a significant reduction in the mean enterocyte height was found after in vitro gluten exposure, compared to culture in basic culture medium. Three patients had coexisting celiac disease and cow's milk protein intolerance. alpha-Lactalbumin and beta-lactoglobulin exhibited toxic effects on flat biopsies from two of these patients, and casein was toxic in one. In 10 patients with cow's milk protein intolerance, a significant reduction in enterocyte height was noted in one case with gluten, and in three patients with casein and lactoglobulin, whereas lactalbumin did not affect the tissues. In seven control patients having a normal duodenal mucosa, no in vitro influences were noted, whereas in four patients with partial villous atrophy, a toxic reaction to gluten was seen in one and a reduced enterocyte height was seen after lactoglobulin exposure in another. In vitro toxicity induced by gluten corresponded well with the diagnosis of celiac disease, whereas toxic reactions to cow's milk proteins during organ culture were inconsistent in cow's milk intolerance, except for cases in which a marked enteropathy was documented.     

Serum IgG and IgA anti-gliadin antibodies as markers of mucosal damage in children with suspected celiac disease upon gluten challenge

Serum anti-gliadin antibodies (AGAs) of the IgG and IgA isotypes were determined in 17 children (mean age of 5.6 years) by means of an enzyme-linked immunosorbent assay (ELISA). All children were suspected of celiac disease. They had been on dietary treatment for at least 10 months before they were challenged with gluten. Based on jejunal biopsy findings, 10 of the 17 children had to be considered positive. The sensitivity of the measurement of AGA at 6 weeks after gluten challenge was found to be 90% for IgG, 100% for IgA, and 100% for IgG/IgA combined. The specificity for IgG, IgA, and the IgG/IgA combination was 100, 71, and 100%, respectively. Twelve weeks after gluten challenge, the sensitivity as well as the specificity of AGA determination for IgG, IgA, and IgG/IgA were 100%. It is concluded that testing both IgG AGA and IgA AGA in children suspected of celiac disease is valuable in monitoring the course of the diagnostic provocation protocol and that jejunal biopsies can be abolished. This inexpensive tool can be useful in reducing the number of intestinal biopsies.     

Antiendomysial antibody detection in biopsy culture allows avoidance of gluten challenge in celiac children

OBJECTIVE: Antiendomysial antibody (EMA) production has been induced in vitro by the small bowel mucosa of celiac disease (CD) patients in clinical remission cultured in the presence of gliadin peptides. The aim of the present study was to use this in vitro system to determine whether it could be used to predict the clinical or histologic relapse to gluten challenge in CD children on a gluten-free diet (GFD). METHODS: Enrolled were 32 CD children and adolescents on GFD (group 1), and 80 controls (group 2) who underwent in vitro gliadin challenge. Subsequently, 24 group 1 CD children underwent in vivo gluten challenge to confirm the diagnosis. Biopsy cultures, with and without gliadin, morphometric analysis, immunoglobulin (Ig)A and IgG1 EMA detection, both in sera and culture supernatants, were performed. RESULTS: Of the 32 group 1 CD patients, 23 were IgA EMA positive in culture supernatants. The other nine were IgG1 EMA positive. All 24 children who had in vivo gluten challenge showed clinical or histologic relapse. All culture supernatants from disease controls belonging to group 2 were both IgA and IgG1 EMA negative, irrespective of gliadin challenge. CONCLUSIONS: Organ culture with in vitro gliadin challenge is able to reproduce the results of in vivo challenge. This system could reduce the need for gluten challenge in celiac children.     

Recombinant human tissue transglutaminase for diagnosis and follow-up of childhood coeliac disease

Highly discriminatory markers for celiac disease are needed to identify children with early mucosal lesions and for rapid follow-up. The aim of this study was to evaluate the potential of circulating anti-tissue transglutaminase (tTG) IgA and IgG antibodies in the diagnosis and follow-up of childhood celiac disease. An ELISA using recombinant human tTG was used to measure the levels of IgA and IgG anti-tTG antibodies in 226 serum samples from 57 children with biopsy-verified celiac disease, 29 disease control subjects, and 24 healthy control subjects. All samples were also analyzed for anti-endomysium antibodies (EMA). The levels of IgA and IgG anti-tTG antibodies correlated with the condition of the small intestinal villous structure and the serum levels of IgA EMA. All of the 25 serum samples obtained from untreated patients contained IgA anti-tTG antibodies, and 24 of 25 also had IgA EMA. Of the serum samples from 53 control children, two had IgA anti-tTG antibodies and two had IgA EMA. Children younger than 5 y of age with untreated celiac disease had the highest serum levels of both IgA and IgG anti-tTG. There was already an increase in IgA anti-tTG antibodies after 2 wk of gluten challenge (p < 0.01). Although the criteria-based diagnosis of childhood celiac disease still depends on histologic evaluation of intestinal biopsies, detection of anti-tTG antibodies provides useful complementary diagnostic information. The human recombinant tTG-based ELISA can be used as a sensitive and specific test to support the diagnosis and may also be used in the follow-up of treatment in childhood celiac disease.     

A comparison between antigliadin antibodies and blood xylose in celiac disease]

We have compared serum antigliadin antibodies (AGA) with xylose absorption test in diagnosis and follow-up of pediatric celiac disease. Three groups of children were investigated: celiacs, affected by other gastrointestinal disease, healthy controls. On gluten diet AGA IgA, IgG and xylose test were abnormal in all celiac children. After only three months of gluten-free diet, abnormal AGA IgA values were found in 3%, AGA IgG in 63%, xylose test in 28% of children. Normal values for AGA IgA and IgG and for xylose test were found between 7 and 20 months. On challenge, after 1-4 months of gluten diet, abnormal AGA IgA and IgG values were found in 90% of cases, xylose test only in 27%. As far as the children with other gastrointestinal disease are concerned, 2% had abnormal values for AGA IgA, 22% for AGA IgG and 42% for xylose test. All healthy children had normal AGA IgA, IgG values and xylose test. Our date show AGA IgA the most specific laboratory test, among these investigated, for diagnosis and follow-up of celiac disease.     

Serum soluble interleukin-2 receptor,interleukin-6, and tumor necrosis factor-alpha levels in children with celiac disease: response to treatment

OBJECTIVES: T-cell mediated immune response to dietary gluten and cytokines release are important for the enteropathy seen in celiac disease. We investigated the serum levels of soluble interleukin-2 receptor, interleukin-6, and tumor necrosis factor-alpha in celiac children before and after gluten exclusion. METHODS: Cytokine levels were determined using enzyme immunoassay in serum from 12 untreated celiac patients, 16 treated celiac patients on a gluten-free diet for at least two years, and from 26 control children. Eight of 12 untreated patients were also investigated at 6 and 12 months after gluten exclusion. Serum IgA antiendomysium antibodies were also assayed by indirect immunofluorescence. RESULTS: Soluble interleukin-2 receptor and interleukin-6 levels were significantly increased in untreated celiac patients compared with treated and control children. There was no difference in the tumor necrosis factor-alpha levels between the groups. Soluble interleukin-2 receptor levels were the only ones significantly decreased at 12 months after gluten exclusion. However, soluble interleukin-2 receptor and interleukin-6 levels at 12 months were significantly higher compared with controls. Antiendomysium antibodies had a diagnostic sensitivity of 100% and the titers decreased significantly after 12 months of gluten exclusion. A significant positive correlation was found between antiendomysium antibody titers with both soluble interleukin-2 receptor and interleukin-6 values. CONCLUSIONS: The serum soluble interleukin-2 receptor and interleukin-6 levels may be used as a noninvasive measure of celiac disease activity and response to treatment.     

Serum antibodies to dietary antigens: a prospective study of the diagnostic usefulness in celiac disease of children

We examined 1,541 consecutive serum samples from 707 children with suspected food intolerance and 32 with treated celiac disease (CD) for IgG and IgA antibody reactivities to antigens from gluten, egg, and cow's milk by an enzyme-linked immunosorbent assay (ELISA). Samples from 72 patients showed increased IgA and/or IgG reactivity to gluten antigens; four were known CD patients not complying with a gluten-free diet, 13 were suspected CD patients challenged with gluten, and 30 most likely had CD as suggested by small intestinal villous atrophy and histological and/or clinical improvement on a gluten-free diet. The remainder with increased antigluten activity had other disorders that might have affected mucosal permeability. Nevertheless, the median IgA reactivity to gluten was significantly higher in the CD group, and the probability for CD increased from 25 to 100% when this reactivity was above 2.4 optical density (OD) units in our ELISA. Sixteen CD patients (but none of those without CD) had IgA reactivity to gluten higher than 2.4 OD units. We conclude that ELISA determinations of levels of serum antibodies reacting to dietary antigens is a valuable adjunct in the diagnosis of CD in children.     

Antiendomysial antibody test reliability in children with frequent diarrhea and malnutrition: is it celiac disease?

BACKGROUND: The aim of this study was to evaluate the specificity of the immunoglobulin A (IgA) antiendomysial antibody test in the diagnosis of celiac disease in a group of malnourished children with acute diarrhea, chronic diarrhea, or parasitosis, because the reliability of this test has been questioned when applied to this specific group of patients. METHODS: Serum IgA level, IgA antiendomysial antibody (EMA) test, and stool examination were performed in 315 children, ranging in age 6 months to 13 years (range, 41 +/- 2.9 months), affected by malnutrition, isolated or in association with diarrhea or parasitosis. Independent of results, 33 children with a strong suspicion of celiac disease, also underwent IgA antitransglutaminase antibody test and jejunal biopsy. RESULTS: The EMA test was negative in 313 children, including the 43 with parasitosis, being positive in two patients in whom biopsy disclosed typical celiac mucosal abnormalities (1:157). The 31 children with negative EMA test who underwent biopsy also showed negative antitransglutaminase antibody results. Their biopsies disclosed normal mucosa in 1 patient, variable degree of jejunal atrophy (grade 1 and 2) in 27 patients, and grade 3 abnormalities in 3 patients. One of these three children, showing severe jejunal atrophy, died. The diagnosis of celiac disease was apparently not confirmed by a protracted gluten challenge in the other two children. CONCLUSIONS: The specificity of the EMA test seems to be high also in children with chronic malnutrition and diarrhea. However, the possibility of false-negative tests among immunologically compromised children cannot be excluded. In doubtful cases, the gluten challenge is required in malnourished children with clinical picture, biopsy finding, and evolution suggestive of celiac disease.     

Anti-gliadin antibody panel and xylose absorption test in screening for celiac disease

We prospectively evaluated the use of a widely used commercially available anti-gliadin antibody (AGA) panel, and compared it with the xylose absorption test in screening pediatric patients with possible celiac disease for small intestinal biopsy. Sixty children were investigated with a 1-h xylose absorption test, IgG and IgA AGA panels, and small bowel biopsy; 15 patients were diagnosed with celiac disease. The xylose was sensitive (93%) but not specific (47%) for celiac disease. The IgA AGA test had high sensitivity (100%) but low specificity (58%), while the IgA AGA test had low sensitivity (53%) but high specificity (93%) in screening for celiac disease. We conclude that the AGA panel currently available in the United States is comparable to, but not significantly different than, the xylose absorption test when used as the only laboratory test in screening for celiac disease. A two-step screening process would have best improved our ability to predict celiac disease. We recommend screening with the AGA panel, and obtaining a xylose test if only the IgG is abnormal. Biopsies should be performed in cases with high IgA AGA, or with abnormal IgG AGA and xylose values. This approach is clinically preferable, does not add cost, and spares children from unnecessary small bowel biopsies.     

Autoantibodies against soluble and immobilized human recombinant tissue transglutaminase in children with celiac disease

OBJECTIVES: The conformation of tissue transglutaminase might influence the performance of immunoassays to detect autoantibodies from patients with celiac disease. The present study investigated how the exposure of tissue transglutaminase kept in a liquid phase and fixed to a solid support affected the binding of immunoglobulin (Ig)A and IgG autoantibodies in children with untreated and treated celiac disease. METHODS: Included were 73 untreated celiac disease children, 50 controls and 80 children with treated celiac disease. IgA and IgG antitissue transglutaminase were measured with solid phase enzyme-linked immunoassay (ELISA) and liquid phase radioligand binding assays. For IgG antitissue transglutaminase detection with radioligand binding assays antihuman IgG and protein A were used. IgA endomysial autoantibodies were measured by indirect immunofluorescence. RESULTS: Both ELISA and radioligand binding assays detected IgA antitissue transglutaminase in 65 of 73 untreated celiac disease children and in 2 of 50 controls. One additional control child was detected with radioligand binding assays. Endomysial autoantibodies were present in 62 of 73 celiac disease children and in 2 of 50 controls. IgG antitissue transglutaminase was detected with both ELISA and radioligand binding assays in 40 of 73 untreated celiac disease children and in 2 of 50 controls. Radioligand binding assays using protein A detected 20 of 73 additional untreated celiac disease children and one control child with increased IgG antitissue transglutaminase. In treated celiac disease children, 21 of 80 were IgA antitissue transglutaminase positive with radioligand binding assays, 3 of 80 with ELISA, whereas none had endomysial autoantibodies. CONCLUSIONS: No qualitative differences between radioligand binding assays and ELISA in IgA or IgG antitissue transglutaminase binding from untreated celiac disease children was demonstrated. However, discrepancies in the binding of IgA antitissue transglutaminase from a subgroup of treated celiac disease children indicated that alterations of tissue transglutaminase might occur on fixation of the antigen. Protein A used for radioligand binding assays seemed not to assess IgG autoantibodies exclusively. IgA antitissue transglutaminase detection in screening of childhood celiac disease can be performed either by ELISA or radioligand binding assays because the two assays are interchangeable.     

Serum IgA and IgG gliadin antibodies and small intestinal mucosal damage in children

Serum immunoglobulin (Ig) A and IgG gliadin antibodies were determined with a simple, rapid, and inexpensive method--diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA)--and the results were related to small intestinal mucosal morphology in 234 children suspected of having malabsorption. Fifty-six of 58 children with flat intestinal mucosa had increased IgA and/or IgG gliadin antibody levels (sensitivity 97%). Fifty-four of the 58 children had celiac disease (CD) (n = 25) or probable CD (n = 29). Four children with flat mucosa had cow's milk protein and/or soy protein intolerance and three of these had increased gliadin antibody levels. Seventeen percent of 132 children with normal intestinal mucosa had increased IgA and/or IgG gliadin antibody levels. IgA and IgG gliadin antibody levels decreased significantly in the celiac children on a gluten-free diet and increased significantly after gluten challenge. Determination of serum IgA and IgG gliadin antibodies by means of DIG-ELISA is a sensitive test for small intestinal mucosal damage in children. When malabsorption is suspected, we suggest that this assay be used to select children for a small intestinal biopsy. It is also very useful for the follow-up of adherence to a gluten-free diet and to determine the effect of gluten challenge in celiac children.     

Anti-alpha-gliadin antibodies are not predictive of celiac disease in juvenile chronic arthritis

Some authors have recently reported an increased level of antigluten antibodies in rheumatoid arthritis, both in the adult and juvenile form. The real meaning of these antibodies is still unclear. We ascertained the levels of antigluten antibodies in a group of children with juvenile chronic arthritis to determine if these antibodies were linked with celiac disease and/or to increased intestinal permeability. In 18 of 53 patients (33.9%), the levels of antigluten antibodies (IgA or IgG) were higher than normal. No correlation was found between the increase in antigluten antibodies and the positive lactulose/ mannitol test, used for determining increased intestinal permeability. In all eight patients undergoing intestinal biopsy due to abnormal levels of antigluten antibodies (IgA class), intestinal mucosa was normal. In conclusion, our study shows that in patients with juvenile chronic arthritis, immunological response to gluten is neither related to celiac disease nor to increased intestinal permeability.     

A new laboratory kit for anti-gliadin IgA at diagnosis and follow-up of childhood celiac disease

A new laboratory kit measuring anti-gliadin IgA level by enzyme immunoassay has been evaluated to assess the test's potential for screening children with suspected celiac disease for small intestinal biopsy and predicting mucosal relapse after gluten challenge. One hundred thirty children were tested, and the results were related to the histopathologic findings of the intestinal mucosa and the final diagnosis. The sensitivity of the test was 97% and the specificity was 92% in the studied population. Forty-five children with celiac disease on different diets were observed. All had reduced anti-gliadin IgA levels on a gluten-free diet, and 91% had normal levels after 1 year. Two of four patients with increased values had an insufficient diet. During gluten challenge, 38 of 45 children showed increased anti-gliadin IgA levels. Of the remaining seven, five reacted either with immediate and strong symptoms or had spontaneously reduced gluten intake, or had an acquired IgA deficiency. In two cases, there was no explanation. In five children without relapse on gluten challenge, the anti-gliadin IgA level remained normal. Provided that IgA deficiency is ruled out and the gluten intake is sufficient, the test is reliable for screening and has a potential to replace the third biopsy.     

Value of Gluten Patch Test in Diagnosis of Celiac Disease

Objective

Celiac disease is an intestinal disorder identified by mucus inflammation, villous atrophy and crypt hyperplasia. This disorder can be controlled by elimination of gluten from daily diet. Patients with celiac disease are at greater risk of gastrointestinal malignancy and non-Hodgkin lymphoma than are the general population. This study tries to present the value of gluten patch test for diagnosis of celiac disease.

Methods

In this investigation, the study population was divided into case and control groups. The case group consisted of patients with celiac disease. The control group were patients involved in celiac disease but suffering from other gastrointestinal disorders. Both gluten patch and placebo patch were attached to the skin between the scapulas. The results were read twice: 48 hours and 96 hours after the patch was applied. Patients who showed irritation reactions were withdrawn from this study. The results were analysed by SPSS software, Spearman''s test, chi square, and Mann–Whitney tests.

Findings

The value obtained from the gluten patch test after 96 hours are as follows: specification at 95%, sensitivity at 8%, positive prediction value at 67%, and negative prediction value at 43%.

Conclusion

It can be concluded that the gluten patch test is not an efficient test for screening of celiac disease, however, it can be useful for diagnosis of celiac disease if employed and studied with clinical symptoms and serologic and biopsy tests. Furthermore, we should doubt our judgment if the result of gluten patch test for the patient with celiac disease is positive.     

Prevalence of celiac disease in Brazilian children with type 1 diabetes mellitus

OBJECTIVE: Although the relationship between celiac disease and diabetes mellitus type 1 is well recognized, there are no studies of this association in Brazil. This study aims to identify the prevalence of celiac disease in a group of children with diabetes mellitus type 1 undergoing treatment in the pediatric endocrinology division of a university hospital in Minas Gerais, Brazil. METHODS: Immunoglobulin (Ig)A and IgG antigliadin antibodies (enzyme-linked immunoadsorbent assay) were measured in blood collected from 236 children and adolescents with diabetes mellitus type 1. Patients with antigliadin antibodies then had jejunal biopsy and determination of antiendomysial antibodies by indirect immunofluorescence. RESULTS: Twenty-one patients had IgA or IgG antigliadin antibodies. Nineteen underwent jejunal biopsy. Six had mucosal alterations compatible with celiac disease; four had nonspecific histologic changes; nine had normal biopsies. Thirteen antigliadin antibody-positive patients were antiendomysial antibody-negative; one antiendomysial antibody-negative patient had celiac disease. The prevalence of celiac disease was 2.6% among 234 patients. CONCLUSIONS: Measurement of antigliadin antibodies in patients with diabetes mellitus type 1 helped in the selection of patients to undergo jejunal biopsy. Antiendomysial antibodies were highly specific and moderately sensitive in predicting celiac disease. The prevalence of celiac disease was higher in diabetics than in the general population, suggesting the need for regular screening assessment of diabetic children.     

IgA antigliadin antibodies in celiac and inflammatory bowel disease

Antibodies against gliadin of the IgA class were assessed with an enzyme-linked immunosorbent assay technique in children with celiac disease, healthy blood donors, and adult patients with active Crohn's disease or ulcerative colitis. Significantly higher antibody values were found in celiac children during gluten challenge and during the first 3 months on a gluten-free diet, compared with the findings in the healthy blood donors. The patients with active Crohn's disease had significantly higher levels of IgA antibodies to gliadin than the controls did. Although the highest values were found in patients with celiac disease on a gluten-containing diet, the difference between the means of these two groups was not statistically significant. No correlation was found between disease activity in ulcerative colitis and antibody values. The present results support the view that high levels of IgA-class antibodies against gliadin are indicative of small intestinal disease, especially celiac disease. The variability of the levels of antibodies found among the patients suggests that not only the amount of gluten in the diet but also other factors are important.     

IgA anti-gliadin antibodies in the monitoring of gluten challenge in celiac disease

The aim of this study was to evaluate the reliability of serum IgA anti-gliadin antibodies (IgA-AGA) in the monitoring of gluten challenge and in the prediction of mucosal relapse in children with celiac disease (CD) in order to reduce the challenging procedure to a minimum. Serial evaluations of serum IgA-AGA titers and 1-h blood xylose levels were performed in 17 children with celiac disease during gluten challenge. Jejunal biopsy was generally done after two consecutive measurements of positive IgA-AGA. The morphological appearance of the mucosa and intraepithelial lymphocyte infiltration were also evaluated. A serum positive for IgA-AGA was observed in 16 of 17 patients between the 15th and 35th day of challenge. The challenge was concluded in all children after 20-45 days from the introduction of a gluten-containing diet after histological confirmation of CD. Plasma xylose test was less reliable in this respect. We conclude that IgA-AGA measurement by gluten challenge is likely to simplify and allow earlier diagnostic confirmation of celiac disease in children, without intestinal biopsy.     

Analysis of anti-gliadin antibodies by immunoblot analysis and enzyme-linked immunosorbent assay using gliadin fractions as antigens.

BACKGROUND: Anti-gliadin antibody (AGA) determination has been widely used in the screening test to detect celiac patients in the general population and in risk groups. Serological assays present variable efficiency, probably caused by differences in the antigenic mixtures employed as antigen. The objective of this work is to evaluate the use of purified gliadin fractions in an enzyme-linked immunosorbent assay (ELISA) test. METHODS: Anti-gliadin antibody reactivity was characterized in the sera of patients with celiac disease, and AGA levels were determined by immunoblot analysis using purified gliadin fractions after separation of wheat proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and acid-PAGE and after indirect ELISA. Seven antigenic mixtures were tested: commercial gliadin, ethanolic wheat extract, and five fast protein liquid chromatography-purified fractions (omega-gliadins, two mixtures of alpha-/beta- and beta-/gamma-gliadins). Immunoblot analysis after A-PAGE separation showed that immunoglobulin (Ig)A reactivity was frequently more restricted than that of IgG. Serum IgA in 15 of 23 patients showed intense reactivity against omega-gliadins. RESULTS: In seven cases, only omega-gliadins were detected. To compare the efficiency of ELISA tests, serum samples of 28 patients with celiac disease and 31 control subjects were tested against the seven gliadin fractions. Immunoglobulin G AGAs demonstrated similar levels against the different gliadin fractions, whereas IgA AGAs showed a heterogeneous reactivity that depended on the fraction tested. The lowest number of false-positive and false-negative results was obtained when the omega-gliadin fraction was used. Parameters for ELISA showed that the omega-gliadin fraction elicited the highest assay efficiency for determinations of both IgA and IgG AGAs. A good correlation was found between IgG and IgA anti-omega-gliadin and antiendomysial antibody determinations. Of the 28 biopsy-confirmed patients with celiac disease, 26 samples (23 positive and 3 negative) were found to have concordant results among the three determinations. CONCLUSIONS: In this study, an intense and, in many cases, selective recognition of omega-gliadins was observed. Results suggest that a higher performance in AGA determination could be achieved using omega-gliadin as an antigen in indirect ELISA.     

Reaction of rectal mucosa of celiac patients to direct contact with gluten

It is assumed that the colonic mucosa of celiac patients is not sensitive to gluten. This assumption has been supported by the absence of clinical manifestations of colonic involvement in patients with active celiac disease which, by itself, does not confirm insensitivity to gluten. Eight children, aged from 11 to 25 months, with an initial diagnosis of celiac disease were studied: in five children a definite diagnosis has already been confirmed. Rectal gluten challenge was done by means of retention enemas. A volume of 100 ml of a 10% gluten suspension in water was introduced into the rectum three times per day for 8 days; each enema was retained at least 1 h. Rectosigmoidoscopies and rectal biopsies were done before and at the end of the challenge period. The endoscopic appearance of rectal mucosa was normal in all the children either before or after gluten challenge. The means of total mucosal thickness, intraepithelial lymphocyte counts, mitotic crypt cell activity, and cellular infiltration of lamina propria increased after challenge; the mean of goblet cell/epithelial cell ratio in the surface epithelium decreased. The differences between each pair of means (before and after challenge), however, were not significant except for total mucosal thickness (p less than 0.05), the meaning of which is unclear. This study did not definitely demonstrate that the rectal mucosa of celiacs is insensitive to gluten. For practical clinical purposes, however, it behaves as such. This makes the rectal mucosa a useless tool for the final diagnosis of celiac disease.     

Zöliakie bei Diabetes mellitus Typ I

Patients and Results

To determine the prevalence of celiac disease in patients with type 1 diabetes and investigate the clinical symptoms, we screened 183 patients with type 1 diabetes for gliadin antibodies (IgA and IgG) and IgA endomysium antibodies. In 14 (7.7%), high antibody titers were found and histology confirmed celiac disease in small-bowel biopsies. Classic symptoms were present in 2. These 14 patients (11 girls, 3 boys) were 4.3 years (mean; 1.0–10.1) old when their diabetes became manifest, 6 having been under 6. Celiac disease was diagnosed at that time or later in all but 1. Three girls also had autoimmune thyroiditis. After 1 year of gluten-free diet BMI-SD increased from 0.01 to 0.36 in 7 prepubertal children. No catch-up growth followed, and no increase in insulin dose per unit of bodyweight or change in frequency of hypoglycemic episodes.

Conclusion

We find celiac disease with surprising frequency in patients with type 1 diabetes; girls with early manifestation of diabetes type 1 seem to be at high risk. Clinical symptoms can be absent, making screening essential in such patients. Long-term studies must determine the importance of gluten-free diet in silent forms of celiac disease.