Antibody testing in Indian children with celiac disease.

BACKGROUND: We prospectively evaluated the usefulness of IgA tissue transglutaminase antibodies (IgA tTG) in the initial diagnosis of celiac disease (CD) and compared its diagnostic potential with that of IgA anti-endomysial antibodies (IgA EMA) and anti-IgA and IgG gliadin antibodies (AGA and AGG, respectively). METHODS: Sera of 23 untreated children fulfilling the revised ESPGHAN criteria for diagnosis of CD (Group I; mean age 10.8 y); 19 disease controls (Group II; mean age 8.5 y) presenting with chronic diarrhea, short stature or both; and 22 healthy children (Group III; mean age 8.8 y) were studied. These were tested in a blinded manner for AGA, AGG, IgA tTG (guinea pig as antigen) and IgA EMA. RESULTS: In Group I, IgA EMA was positive in 19, IgA tTG in 17, AGA in 14 and AGG in 17 patients. In Group II, these tests were positive in 1, 0, 2 and 14 patients, respectively and in Group III, in 0, 0, 0 and 1 child, respectively. Analyzing data from Group I and II, IgA EMA, IgA tTG, AGA and AGG had sensitivity rates of 83%, 74%, 61% and 74%, respectively; the specificity rates were 95%, 100%, 89% and 26%; positive predictive values were 95%, 100%, 88% and 55% and negative predictive values were 82%, 74%, 65% and 45%, respectively. CONCLUSION: IgA tTG is useful for the diagnosis of CD, with sensitivity and specificity rates comparable to those of EMA and this test is well suited for use in tropical countries like India.     

Antiendomysium versus antigliadin antibodies in screening the general population for coeliac disease

BACKGROUND: It has recently been shown that mass screening for coeliac disease, using either the serum antigliadin (AGA) or antiendomysium antibodies (EMA) as screening test, can detect large numbers of cases that had escaped clinical diagnosis. The influence of the diagnostic algorithm on the results of the coeliac screening has not yet been evaluated. Our aim was to compare the validity of the AGA and the EMA protocols in 2096 students living in northwest Sardinia, who took part in a serologic screening for coeliac disease. METHODS: The sample included 2096 of 2345 eligible students (89%) aged 11-15 years who underwent serum IgG AGA, IgA AGA, and IgA EMA determinations. Total serum IgA level was measured in sera showing isolated IgG AGA positivity. Subjects showing at least one of the following: a) EMA positivity, b) IgA AGA positivity, or c) IgG AGA positivity and IgA deficiency (<5 mg/dl) were asked to submit to a small-intestinal biopsy. RESULTS: The prevalence of coeliac disease was 19 (16 showing typical enteropathy, 1 potential case, and 2 known cases) of 2096 (0.91%; 95% confidence interval = 0.50-1.31). Seventeen small-intestinal biopsy specimens were needed to confirm 16 cases of manifest coeliac disease (positive predictive value (PPV) = 94%) by the EMA protocol, whereas the AGA protocol required 21 biopsy specimens for 12 cases of coeliac disease (PPV = 57%). None of six IgA-deficient, IgG AGA-positive cases detected by the AGA protocol also had coeliac disease. CONCLUSIONS: The EMA protocol is superior to the AGA protocol for mass screening of coeliac disease because of higher sensitivity, decreased need for intestinal biopsy, and possibility to detect potential cases of coeliac disease.     

Antiendomysium versus Antigliadin Antibodies in Screening the General Population for Coeliac Disease

Background: It has recently been shown that mass screening for coeliac disease, using either the serum antigliadin (AGA) or antiendomysium antibodies (EMA) as screening test, can detect large numbers of cases that had escaped clinical diagnosis. The influence of the diagnostic algorithm on the results of the coeliac screening has not yet been evaluated. Our aim was to compare the validity of the AGA and the EMA protocols in 2096 students living in northwest Sardinia, who took part in a serologic screening for coeliac disease. Methods: The sample included 2096 of 2345 eligible students (89%) aged 11-15 years who underwent serum IgG AGA, IgA AGA, and IgA EMA determinations. Total serum IgA level was measured in sera showing isolated IgG AGA positivity. Subjects showing at least one of the following: a) EMA positivity, b) IgA AGA positivity, or c) IgG AGA positivity and IgA deficiency (&lt;5 mg/dl) were asked to submit to a small-intestinal biopsy. Results: The prevalence of coeliac disease was 19 (16 showing typical enteropathy, 1 potential case, and 2 known cases) of 2096 (0.91%; 95% confidence interval = 0.50-1.31). Seventeen small-intestinal biopsy specimens were needed to confirm 16 cases of manifest coeliac disease (positive predictive value (PPV) = 94%) by the EMA protocol, whereas the AGA protocol required 21 biopsy specimens for 12 cases of coeliac disease (PPV = 57%). None of six IgA-deficient, IgG AGA-positive cases detected by the AGA protocol also had coeliac disease. Conclusions: The EMA protocol is superior to the AGA protocol for mass screening of coeliac disease because of higher sensitivity, decreased need for intestinal biopsy, and possibility to detect potential cases of coeliac disease.     

Identification of a new coeliac disease subgroup: antiendomysial and anti-transglutaminase antibodies of IgG class in the absence of selective IgA deficiency

OBJECTIVE: The aim of the present study was to increase the sensitivity of the antiendomysial antibody (EMA) test by evaluating also EMAs of IgG1 isotype. DESIGN AND SUBJECTS: Over the last 2 years, serum EMAs IgA and IgG1 were determined in 1399 patients, referred to our gastrointestinal unit due to clinical suspicion of malabsorption. Serum anti-tissue transglutaminase (tTG) antibodies IgA and IgG, as well as total IgA levels, were also investigated. Furthermore, EMAs IgA and IgG1 were evaluated in biopsy culture supernatants. Biopsy specimens were also admitted to histological and immunohistochemical evaluation. Twenty-six patients with gastroenterological disease other than coeliac disease (CD) were used as a disease control group. Ninety-nine blood donors were used as a healthy control group. RESULTS: Diagnosis of CD was based on histological findings in the 110/1399 patients showing EMA IgA positivity, and in a further 56/1399 patients presenting both EMA IgA and IgG1 positivity in sera as well as in culture supernatants. Of the remaining 1233 EMA IgA-negative patients, 60 showed only EMA IgG1 positivity both in sera and in culture supernatants. It is noteworthy that anti-tissue transglutaminase antibodies IgG (anti-tTG) were positive in all 60 EMA IgG1-positive patients as well. By contrast, a selective IgA deficiency was found in only 11 out of the 60 EMA IgG1-positive patients. Villous height/crypt depth ratio was < 3:1 in 38 of the 60 EMA IgG1-positive patients (63.3%), whilst overexpression of ICAM-1 and CD25 was observed in all these patients. CONCLUSIONS: In this study, we observed a group of CD patients who were EMA IgG1-positive even in the absence of EMA IgA positivity and IgA deficiency. The diagnosis was based on the finding of the gluten-dependent clinical and histological features typical of CD. Data emerging from the present investigation thus suggest that the prevalence of CD should be reassessed and that the determination of EMA IgG1 could offer a new tool in the diagnostic armamentarium of CD.     

IgG(1) antiendomysium and IgG antitissue transglutaminase (anti-tTG) antibodies in coeliac patients with selective IgA deficiency. Working Groups on Celiac Disease of SIGEP and Club del Tenue

BACKGROUND: In selective IgA deficiency (IgAD), there is no reliable screening test for coeliac disease (CD). AIM: To evaluate the usefulness of IgG(1) antiendomysium and IgG antitissue transglutaminase tests for CD diagnosis in IgAD. METHODS: IgA and IgG antigliadin antibodies (IgA- and IgG-AGA), IgA and IgG(1) antiendomysium antibodies (IgA- and IgG(1)-EMA), and IgA and IgG antitissue transglutaminase (IgA- and IgG-anti-tTG) were assayed in: (a) 20 untreated IgAD/CD patients; (b) 34 IgAD/CD patients on a strict gluten free diet (GFD); (c) 10 IgAD/CD patients not on a strict GFD; (d) 11 untreated CD patients without IgAD; (e) 10 healthy IgAD patients; and (f) 25 healthy controls. RESULTS: In all untreated IgAD/CD patients, IgG(1)-EMA, IgG-anti-tTG, and IgG-AGA were positive whereas IgA antibodies against these antigens were negative. IgAD/CD patients on a strict GFD did not produce IgG-AGA or IgG(1)-EMA but four of 34 produced IgG anti-tTG. IgAD/CD subjects not on a strict GFD produced IgG-AGA whereas 5/10 and 4/10 were IgG(1)- EMA and IgG-anti-tTG negative, respectively. Untreated CD patients without IgAD were AGA (IgA and IgG), EMA (IgA and IgG(1)), and anti-tTG (IgA and IgG) positive. Healthy controls were AGA and EMA negative whereas two of 10 apparently healthy IgAD subjects and one of 25 healthy negative control were IgG-anti-tTG positive. CONCLUSIONS: Both IgG(1)-EMA and IgG-anti-tTG tests appear to be useful for identification of IgAD/CD patients whereas they are less satisfactory for monitoring dietary compliance in these subjects. In addition, our findings seem to suggest that IgG-EMA autoantibodies produced by coeliac patients are mainly of the IgG(1) subtype.     

Is there an association between familial Mediterranean fever and celiac disease?

Familial Mediterranean fever (FMF) and celiac disease (CD) shares some clinical features such as abdominal pain, diarrhea, arthralgia, and arthritis. Furthermore, both diseases are related to several inflammatory disorders. Based on these analogies, we have investigated whether there is any relationship between CD and FMF. The study had two groups. Group I: 50 children with FMF were questioned and examined for the evidence of CD, serum immunoglobulin A (IgA) levels, antigliadin antibodies (AGA) IgA, AGA IgG, and anti-endomysial antibodies (EMA) IgA were tested, and intestinal biopsy was performed when necessary. Group II: 17 children with CD were evaluated for the presence of clinical and laboratory features of FMF and mutation analysis for MEFV gene was performed to all of them. Six predominant mutations (p.M694V, p.M680I, p.M694I, p.V726A, p.K695R, p.E148Q) in the MEFV gene were studied. The results were as follows-group I: three patients had diarrhea, six had abdominal pain, one had positive AGA IgA, six had AGA IgG, and one had EMA IgA. Intestinal biopsy was performed in one patient who was normal, so none of the patients with FMF were diagnosed as CD and group II: none of the patients with CD had complaints consistent with FMF. Four of the 17 patients (23.5%) were found to carry MEFV mutations. Three of them had heterozygous p.E148Q mutation and one of them had heterozygous p.M680I mutation. None of the FMF patients had CD. MEFV mutation frequency in patients with CD was similar to the normal population in Turkey. Our study did not reveal any association between CD and FMF.     

Coeliac disease in Iraqi type 1 diabetic patients

Background and study aimsHigh prevalence rates of coeliac disease (CD) in patients with type 1 diabetes mellitus (T1DM) have been reported. The aim of this study was to evaluate the frequency of silent CD in a sample of Iraqi patients with T1DM.Patients and methodsThis is a cross-sectional study done in Baghdad Teaching Hospital, Baghdad Medical City, Baghdad, Iraq, on 62 patients with T1DM. For all patients, immunoglobulin A (IgA) anti-tissue transglutaminase antibodies (IgA tTG), IgG anti-tissue transglutaminase antibodies (IgG tTG), IgA endomysial antibody (IgA EMA), IgA antigliadin antibodies (IgA AGA) and IgG antigliadin antibodies (IgG AGA) tests were done, with duodenoscopy, and at least four biopsies were taken from the second part of the duodenum.ResultsA total of 27 patients (43.5%) had normal small-intestinal histopathology (Marsh 0), one of them had a positive result for all serological markers used in the study, and another patient was positive for IgA tTG only. Ten patients (16.1%) had Marsh grade I, one of them was positive for IgA tTG, IgG tTG and IgA EMA, another patient was IgA deficient and had positive IgG tTG only and another patient with Marsh I had positive IgA tTG and IgG tTG only. Two patients (3.2%) had Marsh IIIA; three patients (4.8%) had Marsh IIIB histopathology, two of them were positive for all tests and one had positive IgA tTG and IgA EMA only. Two patients (3.2%) had Marsh IIIC histopathological features; they were positive for all serological tests, hence, the frequency of CD was 11.2%.ConclusionThe frequency of silent CD in Iraqi patients with T1DM is not rare, reaching up to 11.2%. Both EMA and tTG antibodies are useful as screening tests.     

Screening for celiac disease in Down＇s syndrome patients revealed cases of subtotal villous atrophy without typical for celiac disease HLA-DQ and tissue transglutaminase antibodies

AIM: To investigate the prevalence of celiac disease (CD) as well as CD marker antibodies and susceptibility HLA-DQ haplotypes in 134 karyotyped Down's syndrome (DS) patients. METHODS: Immunoglobulin A (IgA) and G (IgG) type anti-gliadin antibodies (AGA), IgA type anti-tissue transglutaminase (tTG) antibodies (anti-tTG) with antigen of guinea pig and human source were determined by enzyme-linked immunosorbent assay and endomysium antibodies (EMA) by indirect immunofluoresence test. HLA-DQA1*0501/DQB1*0201 (DQ2) was revealed by polymerase chain reaction. Celiac disease was diagnosed by revised ESPGHAN criteria. RESULTS: 41% of DS patients had AGA, 6.0% IgA anti-tTG with guinea pig antigen, and 3.0 % IgA EMA (all positive for anti-tTG with human tTG). Subtotal villous atrophy was found in 5 out of 9 DS patients who had agreed to small bowel biopsy. One of them had DQA1*0501/DQB1*0201 and anti-tTG and EMA i.e. typical for CD markers (this case also fulfilled the ESPGHAN diagnostic criteria), but other four lacked these markers. Three non-biopsied DS patients had also most probably CD because DQA1*0501/DQB1*0201 and IgA anti-tTG (EMA) were detected. Thus, the prevalence of CD among our DS patients population is 3.0 % (95 % of confidence interval [CI]: 0.1-5.9 %). CONCLUSION: We confirm the increased frequency of CD among DS patients. In addition, we have revealed a subgroup of patients with subtotal villous atrophy but without characteristic for CD immunological and genetic markers. Whether these cases represent CD (with atypical immunopathogenesis) or some other immune enteropathy, requires further investigations.     

Anti-endomysial Antibody Negative Celiac Disease

Anti-endomysium antibodies (AEM) fail to identify all untreated celiac disease (CD) patients. This study aims to determine if additional serology, in particular, IgA anti-tissue transglutaminase (tTG) antibodies, increases detection. Fifty-three biopsy-proven untreated CD patients (39 women, 14 men; median age 51 years) and 65 control patients with normal duodenal histology (46 women, 19 men; age range 17–90 years, median 45 years) were prospectively studied. Serum total IgA, IgA anti-tTG, IgA AEM, IgA anti-gliadin (AGA) and IgG AGA antibodies were measured. Thirteen (25%) CD patients were AEM negative. None were IgA deficient. Three AEM-negative CD patients had a raised IgA anti-tTG and IgA AGA. IgG AGA was raised in 10 AEM-negative CD patients, but also in 14/65 (22%) of controls. In conclusion, AEM-negative CD is common and detection is only modestly enhanced by testing for IgA anti-tTG antibodies. Duodenal biopsy is still recommended for the accurate diagnosis of CD.     

Antiendomysial antibody detection in fecal supernatants: in vivo proof that small bowel mucosa is the site of antiendomysial antibody production

OBJECTIVES: Serum antiendomysial antibodies (EMAs), highly sensitive and specific serological markers of celiac disease (CD), are detectable in culture media of biopsy samples from CD patients. This finding can be considered an in vitro evidence that intestinal mucosa is a site of EMA production. To confirm this finding, we investigated the presence of EMAs and of anti-tissue transglutaminase (anti-tTG), recently identified as the autoantigen of the EMA, in fecal supernatants of CD patients. METHODS: Twenty-one newly diagnosed CD patients, 10 treated CD patients on a gluten-free diet, and 14 control disease patients on a gluten-containing diet were enrolled. Twenty-four-hour stool collections and fecal supernatants were obtained from all patients in the study. Biopsy cultures were also performed. IgA EMAs were detected in sera, culture media, and fecal supernatants. IgA, IgG, IgM, and IgE anti-gliadin antibodies (AGAs) and IgA anti-tTG antibodies were measured in fecal supernatants. The weights, water content, and pHs of the 24-h stool collections were also measured. RESULTS: In all untreated CD patients EMAs were detectable in sera, culture media, and fecal supernatants. In treated CD patients, EMAs were detected only in culture media after in vitro gliadin challenge. No EMAs were detected in controls. Anti-tTG levels were higher in untreated CD patients than in treated CD patients and controls. IgA AGA levels were higher in untreated CD patients than in treated CD and control patients, whereas IgM AGAs were higher in both untreated and treated CD patients than in controls. No statistically significant differences were observed for IgG and IgE AGAs among the above-mentioned populations. Fecal weights, water content, and pHs were higher in untreated CD than in control patients. CONCLUSIONS: The presence of EMAs in fecal supernatants represents the in vivo proof that intestinal mucosa is a site of EMA production. Furthermore, EMA detection in the stools could be a simple and useful additional tool to clarify diagnosis in the patchy conditions of CD.     

Case-Finding for Adult Celiac Disease in Patients with Reduced Bone Mineral Density

The aim of this study was to assess the value of case-finding for unrecognized adult celiac disease (CD) in patients with reduced bone mineral density (BMD), verified by dual-energy X-ray absorptiometry (DXA). Patients attending for a DXA scan were investigated for CD using immunoglobulins, IgG/IgA antigliadin antibodies (AGA), and endomysial antibodies (EMA). All patients with a positive IgA AGA, EMA, or only IgG AGA in the presence of IgA deficiency had a small bowel biopsy. There were 12 cases of CD (12/978), a prevalence of 1.2% for the whole cohort. The prevalence of CD was 0.7% (2/304) for those with a normal BMD, 1.2% (5/431) for patients with osteopenia, and 2.1% (5/243) for patients with osteoporosis. Direct questioning revealed that all patients with unrecognized CD had subtle gastrointestinal symptoms or a history of anemia. Excluding patients without these symptoms would give a prevalence of 3.9% for osteoporosis (5/127) and 2.6% for osteopenia (5/191). This study suggests that there is no value of unselected case-finding for CD in patients with a reduced BMD. However, a targeted case-finding approach may be more valid and cost-effective with the initial selection of patients who should be investigated for CD based on questioning about gastrointestinal symptoms or anemia.     

Predictive value of serological tests in the diagnosis of celiac disease

In the diagnostic work-up of celiac disease (CD) the simpler enzyme-linked immunosorbent assay (ELISA) for the identification of serum anti-transglutaminase (tTG) autoantibodies could substitute the immunofluorescence technique used for the detection of anti-endomysial antibodies (EmA). However, most of the studies on anti-tTG assay have considered pre-selected groups of patients and not consecutive subjects with suspected CD. The aim of this study was to compare the sensitivity, specificity and predictive value of anti-gliadin antibodies (AGA), EmA and two anti-tTG ELISAs, one based on guinea pig (gp)-tTG and the other on human (h)-tTG as antigens, in consecutive patients investigated for suspected CD. The study included 130 consecutive patients (age range 16-84 years), who underwent intestinal biopsy for suspected CD. They presented with one or more of the following symptoms: weight loss, anemia, chronic diarrhea, abdominal pain, dyspepsia, alternating bowel habits and constipation. At the time of admission in the study, an intestinal biopsy was performed and a serum sample was taken for immunoglobulin (Ig) G and IgA AGA, IgA EmA, anti-gp-tTG and anti-h-TG determination. Intestinal histology revealed that 15 patients had partial or total villous atrophy. In these patients the diagnosis of CD was confirmed at subsequent follow-up. The remaining 115 patients included in the study had an intestinal histology characterized by a normal villi/crypts ratio and were considered as controls. Serum EmA, anti-gp-tTG, and anti-h-tTG were positive in all the 15 CD subjects, whereas IgG and IgA AGA were positive in 10/15; in the control group, none were positive for serum EmA, but 11/115 (10%) were positive for anti-gp-tTG and 6/115 (5%) were positive for anti-h-tTG. The sensitivity was 100% for EmA, gp-tTG and h-tTG and 66% for IgA and IgG AGA. The specificity was 100% for EmA, 90% for anti-gp-tTG, 95% for anti-h-tTG, 74% for IgG AGA and 87% for IgA AGA. The negative predictive value was 100% for EmA, anti-h-tTG and anti-gp-tTG, 94% for IgG AGA and 95% for IgA AGA. The positive predictive value was 100% for EmA, 71% for anti-h-tTG (p = 0.03 vs EmA) and 58% for anti-gp-tTG (p = 0.003 vs EmA). Most of the patients who were false positive for anti-tTG had Crohn's disease or chronic liver disease. In conclusion, although both the anti-tTG ELISAs evaluated in the present study showed an optimum sensitivity, their low specificity determined positive predictive values which were significantly lower than those of EmA assay. Besides, the positive predictive value of gp-tTG was too low to warrant submitting a patient to intestinal biopsy for suspected CD.     

High prevalence of asymptomatic coeliac disease in Norway: a study of blood donors

OBJECTIVE: The prevalence of symptomatic coeliac disease in Norway is 1:675. Coeliac disease has previously been reported in presumably healthy people. Our aim was to determine the prevalence of latent coeliac disease in apparently healthy (i.e. asymptomatic) Norwegian individuals. METHODS: Blood donor sera were tested for gluten antibodies (IgA, IgG). Positive samples (IgA AGA > 0.35, IgG AGA > 0.90) were further tested for endomysium antibodies (IgA EMA). EMA positive individuals were offered gastroenterological investigation. RESULTS: Of 2096 sera, 83 fulfilled the criteria for EMA testing (M/F = 55/28). Eight individuals were EMA positive. On biopsy, seven out of eight had villous atrophy (six subtotal, one partial). None of the patients had significant symptoms. Biochemical data showed iron deficiency (two), hypocalcaemia (one), and low serum zinc (five). All patients were treated with a gluten-free diet and followed up. CONCLUSION: The study indicates a prevalence of 1:340 among asymptomatic and presumably healthy people. This is in keeping with studies from other countries. Lack of symptoms does not exclude secondary deficiency conditions.     

Antibodies to Dietary Antigens in Coeliac Disease

Antibodies to gliadin (AGA) were found in 77 (94%) of 82 sera from patients with active coeliac disease (untreated and after gluten challenge). Although IgG AGA had a higher nosological sensitivity than IgA AGA (88% versus 67%), their nosological specificity was lower than that of IgA antibodies (87% versus 100%). The sensitivity of antibodies to casein, β-lactoglobulin, and ovalbumin in active coeliac disease varied from 36% to 48% without significant difference between IgG and IgA antibodies. IgG and IgA antibodies to milk and egg proteins showed a specificity similar to that of AGA, although some IgA antibodies other than AGA were found in disease controls (Crohn's disease, ulcerative colitis, post-enteritis syndrome).     

IgA antigliadin antibodies and persistence of jejunal lesions in adult coeliac disease

In 46 adult patients with coeliac disease, 41 (89%) of whom were positive for IgA and/or IgG antigliadin antibodies (AGA) when untreated, we investigated after a gluten-free diet the relationship between the persistence of AGA, the persistence of jejunal lesions, and the duration and compliance with the diet. IgG AGA were positive in 21 coeliac patients (46%) after variable periods of gluten-free diet and were associated with IgA positivity only in 4 cases (9%). Both IgA and IgG AGA positivity appeared to be more related to the lack of improvement of the jejunal lesions than to the strictness and duration of gluten withdrawal. Nine coeliacs showed no improvement of jejunal lesions after the gluten-free diet. Of these 9, 4 showed persistent IgA AGA, while the remaining 5 resulted IgAAGA-negative as before when untreated. Though intestinal biopsy remains the best means of determining the positive effect of gluten withdrawal, the persistence of IgA AGA in treated coeliacs is always predictive of the persistence of severe jejunal lesions. The persistence of IgG AGA, on the contrary, should be regarded as an immunological memory.     

Antibodies to dietary antigens in coeliac disease

Antibodies to gliadin (AGA) were found in 77 (94%) of 82 sera from patients with active coeliac disease (untreated and after gluten challenge). Although IgG AGA had a higher nosological sensitivity than IgA AGA (88% versus 67%), their nosological specificity was lower than that of IgA antibodies (87% versus 100%). The sensitivity of antibodies to casein, beta-lactoglobulin, and ovalbumin in active coeliac disease varied from 36% to 48% without significant difference between IgG and IgA antibodies. IgG and IgA antibodies to milk and egg proteins showed a specificity similar to that of AGA, although some IgA antibodies other than AGA were found in disease controls (Crohn's disease, ulcerative colitis, post-enteritis syndrome).     

Elevation of IgG antibodies against tissue transglutaminase as a diagnostic tool for coeliac disease in selective IgA deficiency

BACKGROUND: IgA serum autoantibodies against tissue transglutaminase (tTG) have an established diagnostic value in coeliac disease, and high efficacy tests are widely available for their detection. However, serological evaluation of IgA deficient subjects is still difficult. AIMS: To evaluate the diagnostic potential of IgG class anti-tTG autoantibodies measured quantitatively using an enzyme linked immunosorbent assay (ELISA) compared with immunofluorescent detection of coeliac autoantibodies. PATIENTS: We tested serum samples from 325 IgA deficient subjects, including 78 patients with coeliac disease, 73 disease controls, and 174 blood donors. METHODS: IgG antibodies against human recombinant tTG were measured with an ELISA. IgG antiendomysium antibodies (EMA) were assayed by indirect immunofluorescence on human jejunum and appendix sections. RESULTS: The IgG anti-tTG ELISA had a sensitivity of 98.7% and a specificity of 98.6%, and the correlation with IgG EMA titres was high (r(s)=0.91). One coeliac patient, initially negative in all autoantibody tests, displayed both IgG anti-tTG antibodies and IgG EMA during later gluten exposure. IgG anti-tTG antibodies and EMA titres showed significant decreases (p<0.001) in treated patients. The frequency of IgG anti-tTG autoantibody positivity was 9.8% among IgA deficient blood donors and 11 of the 12 positive subjects with known HLA-DQ haplotypes carried DQ2 or DQ8 alleles. CONCLUSIONS: IgG anti-tTG and IgG EMA autoantibody tests are highly efficient in detecting coeliac disease in IgA deficient patients. The high prevalence of coeliac antibodies among symptom free IgA deficient blood donors who also carry coeliac-type HLA-DQ genes indicates that all IgA deficient persons should be evaluated for coeliac disease.     

Elevated IgA anti-gliadin antibodies in juvenile chronic arthritis.

Increased intestinal permeability secondary to treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and raised levels of anti-gliadin antibodies (AGA) have been reported in adults with rheumatoid arthritis. We have therefore retrospectively investigated the presence of serum AGA of the IgA and IgG classes in 70 patients with juvenile chronic arthritis (JCA). Serum IgA (but not IgG) AGA were found to be higher in JCA patients than in controls (6.2 +/- 8.7 vs 2.1 +/- 1.5 AU/ml; p less than 0.0001). This finding was observed independently of the JCA onset subtype or disease activity; however, lower levels of IgA AGA were found in patients with pauciarticular JCA and in those in remission. No significant differences in IgA AGA serum levels were observed between untreated patients and patients treated with NSAIDs. Five patients who presented the highest levels of IgA AGA were further studied a second time; serum IgA AGA were found to be markedly reduced or normalized and no clinical or laboratory evidence of coexistent coeliac disease was observed. In conclusion, our results suggest that the elevation of IgA AGA seen in our patients is secondary to non-specific immune stimulation rather than to an NSAID-induced increase in intestinal permeability.     

IgA and IgG tissue transglutaminase antibodies in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) and coeliac disease (CD) are diseases of an autoimmune origin that share the human leukocyte HLA-B8 and HLA-DR3 histocompatibility antigens, yet the co-association of CD with SLE is mainly based on case reports. Thus, the real prevalence of CD in SLE is unclear. The aim of this study was to determine the prevalence of antitissue transglutaminase (anti-tTG) in SLE and the relation between SLE and CD. In this case-control study, 100 patients with SLE, and 120 healthy subjects were studied. Sera from all participants were analysed for the presence of IgA and IgG anti-tTG antibodies using a human recombinant tissue transglutaminase (tTG) immuno-enzymatic assay. Anti-tTG positive patients and controls were further tested for antiendomysial (EMA) antibodies by an indirect immunofluorescence and HLA typing (DQalpha1*0501-DQbeta1*0201 allele determination). Subjects who had EMA or the mentioned allele, underwent duodenal biopsy to confirm a possible diagnosis of CD. Anti-tTG antibodies (IgA or IgG isotypes) were found in three of the 100 SLE patients (overall prevalence of 3%): one had the IgA and two the IgG isotypes. Only 1 of 120 healthy subjects (0.8%) had a low positive reaction for IgA anti-tTG. Only the IgA anti-tTG positive SLE patient was diagnosed as having CD based on a positive IgA-EMA and small bowel biopsy findings. The two IgG anti-tTG positive SLE patients and the IgA anti-tTG positive healthy subject were classified as false positives (EMA negative and HLA DQalpha1*0501-DQbeta1*0201 allele negative). In conclusion, anti-tTG antibodies were found at a low rate in SLE patients and mostly did not indicate the presence of CD. Thus, serological screening for CD is not recommended in SLE, unless a clinical suspicion of CD is present.     

Seroreactivity against Saccharomyces cerevisiae in patients with Crohn′s disease and celiac disease

AIM:To explore whether there was anti-Saccharomyces cerevisiae antibodies (ASCA) positivity in our patients with biopsy-confirmed celiac disease.METHODS: A cohort of patients with inflammatory bowel diseases (42 patients with Crohn's disease and 10 patients with ulcerative colitis) and gluten sensitive enteropathy (16patients) from Debrecen, Hungary were enrolled in the study.The diagnosis was made using the formally accepted criteria.Perinuclear antineutrophil cytoplasmic antibodies (pANCA)and antiS-accharomyces cerevisiae antibodies (ASCA),antiendornysium antibodies (EMA), antigliadin antibodies (AGA) and anti human tissue transglutaminase antibodies (tTGA) were investigated.RESULTS: The results showed that ASCA positivity occurred not only in Crohn's disease but also in Celiac disease and in these cases both the IgG and IgA type antibodies were proved.CONCLUSION: It is conceivable that ASCA positivity correlates with the (auto-) immune inflammation of small intestines and it is a specific marker of Crohn's disease.