A controlled,prospective screening study of celiac disease presenting as iron deficiency anemia

BACKGROUND: anemia is the most frequent presenting feature of celiac disease in adults using endomysial antibody (EmA) screening. Endomysial antibody screening of anemia may allow detection of celiac disease at an earlier stage of investigation and after a shorter duration of symptoms. The characteristics of celiac patients identified by screening require further study. GOALS: a goal of this study was to evaluate the prevalence of celiac disease in adult patients with iron deficiency anemia compared with a nonanemic control population using immunoglobulin A (IgA) EmA screening. We also studied the positive predictive value (PPV) of the EmA assay and correlated the severity of histologic abnormalities in distal duodenal biopsy samples with EmA and tissue transglutaminase (tTG) antibody titer. STUDY: four hundred eighty-four patients with microcytic, hypochromic anemia underwent IgA EmA assay. Four hundred ninety-eight nonanemic age- and sex-matched patients from the same source comprised the control group. Patients with positive serology results were invited for endoscopic duodenal biopsies. RESULTS: one in 44 anemic patients was diagnosed with histologically confirmed celiac disease compared with one in 498 nonanemic patients ( < 0.01). Fifty percent of women were premenopausal, and 25% of patients were older than 65 years. The PPV for EmA assay varied between 73% and 93% for anemic patients and improved at higher antibody titer, with all false-positive results occurring at the lowest titers. CONCLUSIONS: screening for celiac disease using IgA EmA assay is effective in anemic patients, including premenopausal women and patients older than 65 years, and it can be recommended in clinical practice.     

IgA antiendomysial antibody test

Serum IgA antiendomysial antibodies (EmA) were found in 61 (87%) of 70 adults and children with untreated celiac disease, whereas IgA antigliadin antibodies (AGA) and IgA R1-antireticulin antibodies (R1-ARA) were positive in 71% and 47%, respectively, of the same patients. Two of the nine untreated celiacs negative for IgA EmA showed positivity for IgA AGA. While IgA AGA and R1-ARA disappeared in all the celiacs tested one year after gluten-free diet, IgA EmA persisted at low titer in seven (18%) of these 38 subjects, although the jejunal biopsy showed a complete regrowth of jejunal villi. All the disease control patients as well as the blood donors tested were always negative for the three IgA antibodies. Our results state that the search for both IgA EmA and AGA gives the best results in the screening of celiac disease, since the positivity for at least one of these two antibodies allows identification with a 100% specificity of the 90% of untreated celiac patients.     

Endomysial antibodies predict celiac disease irrespective of the titers or clinical presentation

AIM: To investigate the association between serum antibody levels and a subsequent celiac disease diagnosis in a large series of children and adults.METHODS: Besides subjects with classical gastrointestinal presentation of celiac disease, the study cohort included a substantial number of individuals with extraintestinal symptoms and those found by screening in at-risk groups. Altogether 405 patients underwent clinical, serological and histological evaluations. After collection of data, the antibody values were further graded as low [endomysial (EmA) 1:5-200, transglutaminase 2 antibodies (TG2-ab) 5.0-30.0 U/L] and high (EmA 1: ≥ 500, TG2-ab ≥ 30.0 U/L), and the serological results were compared with the small intestinal mucosal histology and clinical presentation.RESULTS: In total, 79% of the subjects with low and 94% of those with high serum EmA titers showed small-bowel mucosal villous atrophy. Furthermore, 96% of the 47 EmA positive subjects who had normal mucosal villi and remained on follow-up either subsequently developed mucosal atrophy while on a gluten-containing diet, or responded positively to a gluten-free diet.CONCLUSION: Irrespective of the initial serum titers or clinical presentation, EmA positivity as such is a very strong predictor of a subsequent celiac disease diagnosis.     

Antiendomysium antibodies in Brazilian patients with celiac disease and their first-degree relatives.

BACKGROUND: Literature data have shown high specificity of antiendomysial antibodies (EmA IgA) in celiac disease. The scarcity of Brazilian reports concerning this subject motivated the present study. OBJECTIVES: To determine the sensitivity and specificity of antiendomysial IgA antibodies in Brazilian celiac patients at diagnosis and after treatment, to confirm patient adherence to a gluten-free diet and to screen first-degree relatives. METHODS: An extensive clinical and serological study was performed by investigating the presence of these antibodies in 392 individuals from Southern Brazil. Indirect immunofluorescence using human umbilical cord as substrate was employed and the total levels of IgA were determined by turbidimetry in all groups. The study was conducted on 57 celiac patients (18 at diagnosis, 24 who adhered to a gluten-free diet and 15 with marked or slight transgression of the diet), 115 relatives of celiac patients (39 families), 94 patients with other gastrointestinal diseases, and 126 healthy individuals from the general population. RESULTS: The results demonstrated 100% positivity for the recently diagnosed patients and for those consuming gluten, in contrast to the patients who complied with the diet (0%). In the control group one individual was positive, but refused to undergo a biopsy. In the group of other gastrointestinal diseases, one positive patient presented ulcerative colitis, Down's syndrome and epilepsy, and the intestinal biopsy was diagnostic for celiac disease. These data showed 99.3% specificity for the test. Eighteen relatives were positive for antiendomysial antibodies IgA (15.65%), and comparison with the healthy population revealed a significant difference. An intestinal biopsy was obtained from seven subjects (one with total villous atrophy and six without alterations in the mucosal architecture, but all with a high number of intra-epithelial lymphocytes). CONCLUSIONS: The method revealed 100% sensitivity and 99.3% specificity. Because it is not an invasive method it can be used for the screening of atypical and latent forms of celiac disease to avoid serial biopsies and to control adherence to a gluten-free diet with implications in the prevention of malignancy in celiac disease.     

IgA Antiendomysial Antibodies on the Umbilical Cord in Diagnosing Celiac Disease Sensitivity,Specificity, and Comparative Evaluation with the Traditional Kit

Background: The possibility of assaying antiendomysial antibodies (EmA) on the human umbilical cord instead of monkey esophagus has recently been suggested. We therefore evaluated in patients with celiac disease (CD) the sensitivity and specificity of EmA and of antigliadin antibodies (AGA) for both umbilical cord and monkey esophagus. Methods: We studied 36 patients with CD and atrophy of the intestinal mucosa (median age, 1.4 years), 14 patients with CD on gluten-free diet for 8–12 months (median age, 3.0 years), 36 controls without gastrointestinal disease (median age, 4.0 years), and 72 patients with cow's milk protein enteropathy (CMPE) (median age, 1.2 years). AGA and EmA on monkey esophagus were assayed with commercially available kits; the slides with umbilical cord were prepared in our laboratory. Results: There was a perfect concordance between EmA results evaluated on umbilical cord and those on monkey esophagus; there was a doubtful result in only one case on human umbilical cord, which was positive with low liter on monkey esophagus. EmA specificity was 100%; the specificity of AGA IgG varied between 72% and 94% and of AGA IgA between 90% and 100% depending on whether controls without gastrointestinal disorders or patients with CMPE were considered. EmA sensitivity was 97%, AGA IgG was 89%, and AGA IgA 72% sensitive. The only false negative for EmA was positive for AGA IgG and AGA IgA. Conclusions: Using human umbilical cord as a substrate for EmA may provide the same sensitivity and specificity as offered by the test using monkey esophagus substrate, thus reducing costs and avoiding the use of endangered species.     

Gluten sensitivity in a subset of children with insulin dependent diabetes mellitus

OBJECTIVES: The association between celiac disease and insulin dependent diabetes mellitus (IDDM) is well established. Rectal gluten challenge has been used in patients with celiac disease and in first degree relatives as a tool to assess the mucosal immune response to gluten. The aim of this study was to assess the mucosal immune response to gluten in IDDM children by rectal gluten challenge. METHODS: Rectal biopsy specimens were obtained from 19 children with IDDM before and 6 h after rectal challenge with 2 g of a peptic tryptic digest of gliadin. A total of 16 treated celiac patients and 10 control subjects were also investigated. Epithelium and lamina propria CD3(+) and gamma delta(+) lymphocytes were counted with reference to a standard reference area of muscularis mucosae (10(4) microm(2)). RESULTS: After a local instillation of gliadin, a significant (>mean + 1 SD) percentage increment of lamina propria and epithelium CD3(+) and of lamina propria and epithelium gamma delta(+) lymphocytes was observed in five IDDM children, as compared to 11 and 13 celiac patients and one and two controls, respectively. A discriminant analysis allowed correct classification of 100% of patients with celiac disease and controls. The same analysis classified four of 19 IDDM children in the group of celiac patients. The positivity was associated with normal serology (antigliadin antibody, antiendomysial antibody, and antitissue transglutaminase antibodies) and a morphologically normal jejunal mucosa. All four patients had HLA-DQ alleles associated with celiac disease. CONCLUSIONS: Approximately 20% of IDDM children react to rectal instillation of gliadin. Long term follow-up is necessary to establish whether these subjects are at increased risk for developing celiac disease.     

Disappearance of endomysial antibodies in treated celiac disease does not indicate histological recovery

OBJECTIVE: Although serum IgA-class endomysial antibody (EmA) has high sensitivity for villous atrophy (VA) in patients with untreated celiac disease, few studies have attempted to correlate EmA seroconversion with histological recovery after starting a gluten-free diet. We prospectively studied changes in EmA status and in duodenal histology of seropositive patients after dietary treatment. METHODS: Patients with VA and EmA had repeat EmA testing at 3, 6, and 12 months after starting gluten-free diet, plus assessment of dietary compliance by dietitians and follow-up duodenal biopsy at 12 months. VA before and after treatment was classified as partial (P), subtotal (ST), and total (T). RESULTS: Of 77 patients with newly diagnosed VA and without IgA deficiency, 62 (81%) had EmA: 46 of 57 (81%) with T or STVA and 16 of 20 (80%) with PVA. Of 53 initially EmA-positive patients who completed study criteria, EmA was undetectable in 31 patients (58%) after 3 months' diet, in 40 (75%) after 6 months, and in 46 (87%) after 12 months. However, only 21 patients (40%), all seronegative by 12 months, had complete villous recovery. Only three (33%) of 10 patients with persisting ST or TVA and two (9%) of 22 with PVA remained EmA positive. Four of the five patients with persisting EmA had poor dietary compliance. CONCLUSIONS: EmA is a poor predictor of persisting VA after patients have started gluten-free diet, although it may be of value in monitoring dietary compliance. Although there are no clear guidelines regarding the need for follow-up biopsy, EmA seroconversion cannot substitute. The apparent association between dietary compliance and seroconversion suggests that gluten intake may determine whether untreated celiac patients are EmA positive or negative for a given degree of small bowel damage.     

HLA-DQ typing in the diagnosis of celiac disease

OBJECTIVE: More than 95% of celiac patients share the major histocompatibility complex II class human leukocyte antigen (HLA) DQ2 or DQ8 haplotype; patients negative for both types are unlikely to suffer from celiac disease. Our aim was to investigate whether HLA-DQ2 and -DQ8 typing is helpful when diagnosis is uncertain because of the absence of unequivocal small bowel villous atrophy. METHODS: HLA-DQ2 and -DQ8 typing was carried out in 59 patients evincing nondiagnostic small bowel mucosal lesion or positive celiac serology, and in 17 patients maintaining a gluten-free diet without biopsy-proven celiac disease. HLA findings were compared to small bowel mucosal morphology; intraepithelial lymphocytes; and serum endomysial (EmA), reticulin, tissue transglutaminase (anti-tTG) and gliadin antibodies. RESULTS: Of the 59 patients evincing only minor small bowel mucosal changes or positive celiac disease serology, 22 (37%) were negative for DQ2 and DQ8. All EmA-positive patients had celiac-type HLA, but antireticulin antibody, anti-tTg, and antigliadin antibody were also present in HLA-DQ2- and -DQ8-negative individuals. Eleven of 17 patients (65%) observing a gluten-free diet before small bowel biopsy did not share celiac-type HLA. None of the 17 had apparent villous atrophy. Serum EmA and anti-tTG were negative in all. HLA-DQ typing is less expensive than follow-up biopsy in the exclusion of celiac disease. CONCLUSIONS: HLA-DQ2 and -DQ8 determination is useful in exclusion, probably lifelong, of celiac disease in individuals with an equivocal small bowel histological finding. The low specificity of this test must, however, be borne in mind.     

High prevalence of celiac disease in patients with type 1 diabetes detected by antibodies to endomysium and tissue transglutaminase.

OBJECTIVE: To establish the prevalence of celiac disease (CD) in children with type 1 diabetes in British Columbia. PATIENTS AND METHODS: Two hundred thirty-three children with type 1 diabetes were prospectively screened for CD using blind testing with the current 'gold standard', immunoglobulin A endomysium antibody (EmA), and the novel immunoglobulin A tissue transglutaminase (tTG) antibody. Those children with positive results were offered small bowel biopsy; a gluten-free diet was recommended if CD was confirmed. RESULTS: Nineteen children were positive for EmA and had an elevated tTG level. One patient from this group was already known to have CD, and the other 18 patients consented to biopsy. One biopsy was normal, three biopsies demonstrated elevated intraepithelial lymphocyte counts with normal morphology and 14 biopsies had morphological changes consistent with CD. Growth parameters were normal in all patients, and nine of 19 children who were positive for EmA were asymptomatic. Seven patients had mild elevation of tTG levels alone. Two children from this latter group had normal biopsies, and five declined biopsy. CONCLUSIONS: At least 14 new cases of CD were detected in addition to four known cases, yielding an overall biopsy-confirmed prevalence of CD of 7.7% (18 of 233). The present study confirms that CD is as prevalent in the pediatric type 1 diabetic population in British Columbia as it is in Europe. Serological screening of these children is important because many children have no symptoms or signs suggestive of CD. This study suggests that tTG serology may also be useful in monitoring response and compliance with a gluten-free diet.     

Detection of autoantibodies against tissue transglutaminase in patients with celiac disease and dermatitis herpetiformis

OBJECTIVE: Endomysial autoantibodies (EmA) are specific for celiac disease. The target antigen has been identified as tissue tranglutaminase (tTG). Our aim was to study the accuracy of a newly developed enzyme-linked immunosorbent assay (ELISA) for easy detection of tTG autoantibodies. METHODS: Thirty-one sera from patients with histologically proven celiac disease and 23 healthy controls were examined for EmA using monkey esophagus and human umbilical cord as substrate. IgA-tTG autoantibodies were determined by newly developed ELISA. Additionally, sera from patients with dermatitis herpetiformis (n = 20), inflammatory bowel disease (IBD; n = 32), chronic liver disease (n = 36), and diabetes mellitus (n = 19) were tested. RESULTS: The sensitivity of the tTG autoantibody ELISA accounted for 90% detection in patients with untreated celiac disease. The specificity was 76% owing to positive values in the lower range in patients with IBD (15%), chronic liver disease (36%), and diabetes (22%), all of whom were negative for EmA. In dermatitis herpetiformis patients 90% were EmA-positive. Of these, only 47% showed elevated tTG autoantibodies. Preincubation of sera from dermatitis patients with tTG abolished immunofluorescent staining of endomysial structures. CONCLUSION: Detection of mid- to high-titer tTG autoantibodies is highly specific for celiac disease. However, in the low-titer range, overlap exists with liver disease, IBD, and diabetes. Tissue transglutaminase autoantibodies may evolve as a new screening and follow-up method for celiac disease. Although tTG seems to be a major autoantigen in dermatitis herpetiformis, the low sensitivity of both tTG ELISA and immunofluorescence using human umbilical cord suggests differential involvement of tTG in this disease.     

IgA antibodies to jejunum

Serum IgA antibodies to jejunum (JAB) were found in 78 (96%) of 81 adults and children with untreated celiac disease. Not only did IgA JAB display a significant higher prevalence than IgA antigliadin antibodies (AGA) (72%) in untreated gluten-sensitive enteropathy, but they also allowed us to identify another three celiacs in addition to those detected by IgA antiendomysial antibodies (EmA). Like IgA EmA, IgA JAB persisted at low titer in seven (14%) of 50 celiacs tested after 12 months of gluten-free diet (GFD) despite the regrowth of jejunal villi, whereas IgA AGA disappeared in all these patients consistently with the normalization of intestinal mucosa. IgA JAB and EmA reappearance was close to 100% in the 13 celiacs studied after six months of gluten challenge, while IgA AGA reached the highest prevalence (about 70%) after one month of gluten ingestion without any increase in the following months. All disease and healthy controls were always negative for the three IgA antibodies. Our results prove that IgA JAB and EmA are the best screening tests for active (untreated and on gluten challenge) celiac disease, whereas IgA AGA should be used for monitoring the response to gluten withdrawal. IgA JAB are an expression of a specific immunity directed against the target organ of gluten-sensitive enteropathy, but, before ascribing them a role in the pathogenesis of celiac disease, it should be ascertained whether their production is a primary event leading to jejunal lesions or whether it is a secondary phenomenon due to antigen release from a previously damaged jejunal mucosa.     

Comparison of IgA endomysium antibody and IgA tissue transglutaminase antibody in celiac disease.

The antigen for immunoglobulin (Ig) A endomysium antibody (EmA), a sensitive and specific serological marker for celiac disease, has recently been described as tissue transglutaminase (tTG). The aim of this study was to compare the assays used to measure IgA EmA and IgA tTG antibody in patients with celiac disease and disease control subjects. Sera from 21 patients with untreated celiac disease, 48 patients with treated celiac disease and 128 disease control subjects were tested both for IgA EmA with the use of indirect immunofluorescence against human umbilical cord and for IgA tTG antibody with the use of ELISA. Titres of IgA tTG antibody were significantly higher in both the untreated and treated celiac groups than in the disease control group. Titres in the treated group were, however, significantly lower than in the untreated group. A reference range was calculated to include 99.8% of the disease control group in whom small bowel biopsy showed no evidence of celiac disease. One patient from the disease control group with raised IgA tTG antibody titres and positive IgA EmA was found to have celiac disease on small bowel biopsy. The sensitivity, specificity, and positive and negative predictive values of the IgA EmA assay were all 100%. The sensitivity of the IgA tTG antibody assay was 95%, specificity 100%, positive predictive value 100% and negative predictive value 97.7%. An ELISA used to measure IgA tTG antibody is an excellent tool to screen for celiac disease and may prove useful for monitoring response to treatment.     

Longitudinal follow-up examination of antigliadin antibody positive children and adults

BACKGROUND: We previously investigated the prevalence of asymptomatic celiac disease in 3004 healthy children and 4313 adult blood donors by screening for IgA and IgG class antigliadin antibodies (AGA) and IgA class anti-endomysial antibodies (EmA). In none of the 162 exclusive AGA-positive adults and in only one of the 117 exclusive AGA-positive children could celiac disease be diagnosed. We followed up AGA-positive individuals in respect of the significance of the AGA. METHODS: All AGA-positive children and adults were invited for a follow-up clinical examination and laboratory investigations including AGA-IgA, AGA-IgG and EmA. Celiac disease-specific antibodies were also determined in stool samples. RESULTS: Sixty-nine adults and 47 children returned for follow-up. In 26 (37.7%) cases of the 69 adults formerly tested AGA-positive, AGA were still detectable after an average period of 3.7 years. In 21 (44.7%) cases of 47 formerly AGA-positive children, AGA were still detectable after an average period of 4.3 years. None of the 69 adults and 47 children showed seroconversion to EmA. There were no significant abnormalities in the laboratory results or any clinical signs of enteropathy.The appearance of fecal and serum antibodies was compared in 112 subjects but no correlation between fecal and serum antigliadin antibodies was found. CONCLUSIONS: In both studied populations of adults and children, AGA disappeared in more than 50% of the cases. The appearance of AGA has to be interpreted as a non-specific immunomodulation phenomenon, confirming the low specificity of AGA as a serologic marker for celiac disease.     

Increased prevalence of celiac disease in girls with Turner syndrome detected using antibodies to endomysium and tissue transglutaminase.

OBJECTIVE: To establish the prevalence of celiac disease (CD) in girls with Turner syndrome (TS) in British Columbia. METHODS: Forty-five girls with TS were prospectively screened for CD using blinded testing with the current 'gold standard' - immunoglobulin A (IgA) endomysium antibody (EmA) and the novel IgA tissue transglutaminase antibody (tTG). Those with positive results were offered small bowel biopsies, and a gluten-free diet was recommended if CD was confirmed. RESULTS: One asymptomatic prepubertal East Indian girl was positive for EmA, had an elevated tTG concentration of 560 U/mL and histological evidence of CD. Seven girls were negative for EmA but had elevated tTG concentrations (175 to 250 U/mL); five were white, one was Asian and one was East Indian. Small bowel biopsies were performed on three girls, and the histologies were normal. The remaining four patients declined biopsy. CONCLUSIONS: One girl with TS was identified with CD from 45 screened, giving an overall biopsy-confirmed prevalence of 2.2%. This study confirms previous observations placing girls with TS at higher risk for CD and suggests a similar high prevalence in British Columbia.     

Prevalence of serum celiac antibody in patients with IBD in Japan

Background

Although the incidence of inflammatory bowel diseases (IBD) in Japan has increased, the prevalence of celiac disease is considered very low with the lowest genetic disposition. IBD is reported as the most common comorbidity because of the high positive rate of serological celiac markers. The aim of this study was to examine the current incidence of celiac disease, especially in IBD patients in Japan, where both wheat consumption and incidence of IBD have increased.

Methods

A total of 172 patients with IBD and 190 controls in Japan were screened for serum antibody of tissue transglutaminase and deaminated gliadin peptide. In sero-positive patients, HLA testing and upper gastrointestinal endoscopy with duodenal biopsy was performed. Some of the sero-positive patients started a gluten-restricted or unrestricted diet, and serological change was determined.

Results

The positivity of both serum antibodies was significantly higher in IBD and correlated with disease activity. However, no biopsy-defined or HLA-defined true celiac disease was found. A decrease in serum antibody titers was observed with a gluten-restricted diet.

Conclusions

Despite the increased incidence of IBD and high positivity for serum celiac antibody in Japanese IBD patients, no true-positive celiac disease was noted, suggesting the presence of gluten intolerance in these populations.     

Enteric glial-derived S100B protein stimulates nitric oxide production in celiac disease

BACKGROUND & AIMS: Enteric glia participates to the homeostasis of the gastrointestinal tract. In the central nervous system, increased expression of astroglial-derived S100B protein has been associated with the onset and maintaining of inflammation. The role of enteric glial-derived S100B protein in gastrointestinal inflammation has never been investigated in humans. In this study, we evaluated the expression of S100B and its relationship with nitric oxide production in celiac disease. METHODS: Duodenal biopsy specimens from untreated and on gluten-free diet patients with celiac disease and controls were respectively processed for S100B and inducible nitric oxide synthase (iNOS) protein expression and nitrite production. To evaluate the direct involvement of S100B in the inflammation, control biopsy specimens were exposed to exogenous S100B, and iNOS protein expression and nitrite production were measured. We also tested gliadin induction of S100B-dependent inflammation in cultured biopsy specimens deriving from on gluten-free diet patients in the absence or presence of the specific S100B antibody. RESULTS: S100B messenger RNA and protein expression, iNOS protein expression, and nitrite production were significantly increased in untreated patients but not in on gluten-free diet patients vs controls. Addition of S100B to control biopsy specimens resulted in a significant increase of iNOS protein expression and nitrite production. In celiac disease patients but not in controls biopsy specimens, gliadin challenge significantly increased S100B messenger RNA and protein expression, iNOS protein expression, and nitrite production, but these effects were completely inhibited by S100B antibody. CONCLUSIONS: Enteric glial-derived S100B is increased in the duodenum of patients with celiac disease and plays a role in nitric oxide production.     

Celiac disease in adult patients with type 1 diabetes mellitus in Tunisia

OBJECTIVE: Type1 diabetes mellitus may be associated with celiac disease. The prevalence of celiac disease as determined by screening among adult patients with type 1 diabetes is high with rates of 1.07.8% in Europe and U.S.A. The aims of the study are to determine the prevalence of celiac disease in adults with type 1 diabetes in Tunisia. METHODS: 348 consecutive adult patients with type1 diabetes were investigated prospectively and screened for celiac disease. The mean age was 28.45+/-10.74 years old. There were 176 females and 172 males. For the screening of celiac disease, we used immunoglobulin A (IgA) anti-endomysium (EMA) antibodies determined by an indirect immunofluorescence method. Anti-transglutaminase (tTG) antibodies were determined by an ELISA method. Those patients with positive results for anti EMA and or tTG were proposed for duodenal biopsy. RESULTS: 14 patients were positive for anti EMA and had high or a weak positive level of tTG antibodies. One patient from this group was already known to have celiac disease. Only 8 patients consented to biopsy and morphological changes were consistent with celiac disease in all cases. Prevalence of biopsy-proven celiac disease was 2.3% (95% CI=1.0-4.5%). CONCLUSION: The present study confirms that celiac disease of adults is prevalent in type 1 diabetic patients in Tunisia. Serological screening for celiac disease in type 1 diabetes is important because many patients are asymptomatic and most are detected by the screening.     

Unusual association of thyroiditis, Addison's disease, ovarian failure and celiac disease in a young woman.

The coexistence of autoimmune endocrine diseases, particularly autoimmune thyroid disease and celiac disease (CD), has recently been reported. We here present a 23-year-old woman with a diagnosis of hypothyroidism due to Hashimoto's thyroiditis, autoimmune Addison's disease, and kariotypically normal spontaneous premature ovarian failure. Considering the close association between autoimmune diseases and CD, we decided to search for IgA anti-endomysium antibodies (EmA) in the serum. The positivity of EmA and the presence of total villous atrophy at jejunal biopsy allowed the diagnosis of CD. On a gluten-free diet the patient showed a marked clinical improvement accompanied, over a 3-month period, by a progressive decrease in the need for thyroid and adrenal replacement therapies. After 6 months, serum EmA became negative and after 12 months a new jejunal biopsy showed complete mucosal recovery. After 18 months on gluten-free diet, the anti-thyroid antibodies titre decreased significantly, and we could discontinue thyroid substitutive therapy. This case emphasizes the association between autoimmune polyglandular disease and CD; the precocious identification of these cases is clinically relevant not only for the high risk of complications (e.g. lymphoma) inherent to untreated CD, but also because CD is one of the causes for the failure of substitute hormonal therapy in patients with autoimmune thyroid disease.     

Autoantibodies to tissue transglutaminase are sensitive serological parameters for detecting silent coeliac disease in patients with Type 1 diabetes mellitus.

AIMS: To investigate the clinical significance of the determination of IgA antibodies to tissue transglutaminase (tTG) for the detection of silent coeliac disease in patients with Type 1 diabetes mellitus. METHODS: A total of 520 patients with diabetes (median age 14.2 years, range 1-27) were tested for IgA antibodies to tTG (IgA anti-tTG, ELISA), endomysium (EmA, indirect immunofluoresence) and gliadin (IgA-AGA, enzyme immunometric assay) after ruling out IgA deficiency. RESULTS: The prevalence of IgA anti-tTG among patients with diabetes was 4.4% (23 of 520), and that of EmA and IgA-AGA 3.5% (18 of 520, respectively). The coefficient of agreement between IgA anti-tTG and EmA was high (Cohen's kappa = 0.87, P < 0.001). Thirteen of the 23 IgA anti-tTG-positive patients underwent duodenal biopsy. Coeliac disease was confirmed in nine of 13 patients. One of them was negative for EmA and AGA, but positive for IgA anti-tTG. Retrospective annual determinations up to 8 years in six IgA anti-tTG-positive patients showed both permanent and transient elevations of the serological markers. CONCLUSIONS: These data show that a positive IgA antibody test to tTG is a more sensitive parameter than EmA for silent coeliac disease in patients with diabetes. Confirmatory small bowel biopsy, however, remains necessary for diagnosis as some patients with positive antibodies may be without histological changes.