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.     

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.     

Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice

OBJECTIVE: We have undertaken a study to assess the efficiency of serological tests in the diagnosis of celiac disease (CD) during the period January 1, 1994 to January 7, 1997. Our aim was to evaluate the sensitivity of IgA antiendomysium (EMA) and IgA antigliadin (AGA) with regard to the degree of histological abnormality in biopsy specimens of small intestine in untreated celiac disease patients and first-degree relatives. METHODS: The study population comprised 101 cases: 85 untreated celiac patients and 16 first-degree relatives with a mean age of 42 yr (range, 2-76 yrs). Sixteen of 85 were excluded from study because they did not satisfy the study or diagnostic criteria of CD. EMA and AGA have been compared with the degree of villous atrophy (VA) in 69 celiac patients and 16 relatives according to the Marsh criteria of 1992. We divided the Marsh III histology into three subgroups as follows: Marsh IIIa (partial VA), Marsh IIIb (subtotal VA), and Marsh IIIc (total villous atrophy). RESULTS: The specificity and positive predictive value of EMA for CD was excellent, because all EMA-positive patients (n = 42) were diagnosed with CD. The sensitivity of EMA, however, differed between CD subgroups; in patients with total VA, the sensitivity of EMA was 100% (17/17). However, in patients with partial VA (Marsh IIIa), the sensitivity of EMA was disappointing, only 9/29 (31%). Three of 72 celiacs with Marsh IIIb and Marsh IIIc had IgA deficiency and were excluded from the study. Elevated AGA has been detected in the sera of 39 of 69 (62%) patients. A combination of EMA and AGA tests showed a sensitivity of 76% (53/69). None of 16 first-degree relatives with Marsh I-II had positive EMA. CONCLUSIONS: Interpretation of negative serology needs great awareness. Although EMA sensitivity in total villous atrophy is excellent, in partial villous atrophy the sensitivity of EMA appears to be disappointing. Our experience shows that EMA and AGA have only limited value in screening programs for CD.     

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.     

Should relatives of coeliacs with mild clinical complaints undergo a small-bowel biopsy despite negative serology?

BACKGROUND AND OBJECTIVES: Small intestinal lesions in coeliac disease (CD) have a variable severity. Early diagnosis of CD is important because treatment allows a normal psycho-physical development, especially in children, and can avoid associated disorders. The aim of this study was to evaluate the predictive value of screening parameters for the detection and estimation of CD prevalence in first-degree relatives. METHODS: The screening was performed in 338 first-degree relatives of 134 coeliac families. Questionnaires and a physical examination followed by haematological analyses and serologyfor IgA anti-endomysium (EMA)/IgA antigliadin (AGA) antibodies were used in orderto selectthe candidates for small-bowel biopsy. The small-bowel biopsy was indicated on the basis of clinical complaints, laboratory tests and serology performed in 96 (28%) of the study group. RESULTS: CD was diagnosed in 17/96 cases. Six of the 17 showed total villous atrophy (VA) (Marsh IIIc), five subtotal VA (Marsh IIIb) and six partial VA (Marsh IIIa). EMA and AGA were strongly positive in the six patients whose intestinal biopsy showed total VA. However, only one coeliac out of the six patients with partial VA had positive EMA and AGA. CONCLUSION: A significant proportion of coeliacs may be missed if cases are screened by serology only. Although endomysial antibody assay has been reported as a highly sensitive and specific test for detection of CD, we argue that using only EMA and AGA in screening is not enough for investigation of the true prevalence of CD. A combination of clinical parameters as described in this study and laboratory/serological tests is an important and practical contribution to improving the detection rate of CD.     

The frequency of the celiac disease among children with familial Mediterranean fever

We aimed to assess the frequency of celiac disease (CD) in patients with Familial Mediterranean Fever (FMF). This prospective study was carried out from October 2015 to March 2016 and included 303 patients with FMF. We used 98 sex- and age-matched healthy subjects as a control group. Levels of total IgA and tissue transglutaminase (tTG) IgA antibody were measured in all groups. Those with increased level of tTG IgA were tested for anti-endomysium IgA antibodies (EMA). Patients with positive EMA underwent gastro-duodenoscopy and intestinal biopsy for a definite diagnosis of CD. Only 9 of 303 patients (2.9%) were positive for tTG IgA. Patients positive for tTG IgA were then tested for EMA and only one of them (0.3%) had a positive result. This patient underwent gastro-duodenoscopy. The pathological report was compatible with Marsh 0 classification score for the diagnosis of CD. Two subjects from the control group were positive for tTG IgA but none of them had positive EMA antibodies. We did not find CD in the large cohort of childhood FMF patients. The prevalence of CD did not show association with presence of childhood FMF in this study and CD would not be a considerable complication of childhood FMF.     

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.     

Effectiveness of the sorbitol H2 breath test in detecting histological damage among relatives of coeliacs

BACKGROUND: Small intestinal lesions have a wide severity in coeliac disease (CD), and early diagnosis is important in preventing neoplastic and non-neoplastic disorders related to CD. The aim of this study was to compare the effectiveness of the sorbitol H2 breath test (H2-BT) and serological tests (antigliadin (AGA), antiendomysium (EMA) and anti-tissue transglutaminase (anti-tTG)) as screening tests in the detection and estimation of CD prevalence in 1st-degree relatives. METHODS: Screening was performed in 111 1st-degree relatives of 37 coeliac families. Sorbitol H2-BT, AGA, EMA and anti-tTG antibodies were used to select the candidates for small-bowel biopsy. Relatives with abnormal serological tests and/or with sorbitol H2-BT positivity underwent a small-bowel biopsy. Small-bowel biopsy was also performed in relatives negative in all tests but with clinical complaints or suspected of having CD, and intestinal lesions were expressed according to the Marsh classification. RESULTS: CD was diagnosed in 49/111 screened relatives (44.14%): 5 showed Marsh IIIc, 8 Marsh IIIb, 16 Marsh IIIa, 13 Marsh II and 7 Marsh I lesions. Nineteen relatives showed the classical form of the disease, while the subclinical and silent forms were recorded in 20 and 10, respectively. AGA, EMA and anti-tTG showed strong positivity only in severe intestinal damage (Marsh IIIb-c lesions) (but overall positivity was 36.73%, 38.78% and 44.89% for AGA, EMA and anti-tTG, respectively), while sorbitol H2-BT showed strong positivity also in patients with slight histological damage (Marsh I-IIIa) (overall positivity was 83.67%). CONCLUSIONS: A significant proportion of coeliacs may be missed if relatives are screened by serology only, while the efficacy of sorbitol H2-BT in screening relatives is confirmed. This study confirms that neither a breath test nor serology can replace intestinal biopsy, which remains the gold standard for the diagnosis of CD.     

Effectiveness of the Sorbitol H 2 Breath Test in Detecting Histological Damage Among Relatives of Coeliacs

Background: Small intestinal lesions have a wide severity in coeliac disease (CD), and early diagnosis is important in preventing neoplastic and non-neoplastic disorders related to CD. The aim of this study was to compare the effectiveness of the sorbitol H 2 breath test (H2-BT) and serological tests (antigliadin (AGA), antiendomysium (EMA) and anti-tissue transglutaminase (anti-tTG)) as screening tests in the detection and estimation of CD prevalence in 1st-degree relatives. Methods: Screening was performed in 111 1st-degree relatives of 37 coeliac families. Sorbitol H2-BT, AGA, EMA and anti-tTG antibodies were used to select the candidates for small-bowel biopsy. Relatives with abnormal serological tests and/or with sorbitol H2-BT positivity underwent a small-bowel biopsy. Small-bowel biopsy was also performed in relatives negative in all tests but with clinical complaints or suspected of having CD, and intestinal lesions were expressed according to the Marsh classification. Results: CD was diagnosed in 49/111 screened relatives (44.14%): 5 showed Marsh IIIc, 8 Marsh IIIb, 16 Marsh IIIa, 13 Marsh II and 7 Marsh I lesions. Nineteen relatives showed the classical form of the disease, while the subclinical and silent forms were recorded in 20 and 10, respectively. AGA, EMA and anti-tTG showed strong positivity only in severe intestinal damage (Marsh IIIb-c lesions) (but overall positivity was 36.73%, 38.78% and 44.89% for AGA, EMA and anti-tTG, respectively), while sorbitol H2-BT showed strong positivity also in patients with slight histological damage (Marsh I-IIIa) (overall positivity was 83.67%). Conclusions: A significant proportion of coeliacs may be missed if relatives are screened by serology only, while the efficacy of sorbitol H2-BT in screening relatives is confirmed. This study confirms that neither a breath test nor serology can replace intestinal biopsy, which remains the gold standard for the diagnosis of CD.     

Population screening for coeliac disease in a low prevalence area in Italy

OBJECTIVE: A screening program was proposed for the village of Carcare (population 5700), located in a region of Italy with an apparently low prevalence of coeliac disease (CD): only 1 patient diagnosed out of 2557 inhabitants. The study group comprised 1002 individuals (568 F, 434 M, age range 13-90 years) recruited from blood donors, secondary school pupils and people referred to the local outpatient facilities for routine blood chemistry. MATERIAL AND METHODS: Total IgA, IgA anti-tissue transglutaminase (tTG) (ELISA, recombinant human antigen) and IgA antiendomysium (EMA) (IFI, umbilical cord substrate) antibodies were measured in the serum of all participants. All patients with IgA deficiency were investigated for IgG tTG antibodies, and in the case of disagreement between tTG and EMA, they were typed for HLA DQ2-DQ8 haplotypes. RESULTS: Thirteen subjects were positive and 988 negative for autoantibodies (3/988 had IgA deficiency). One serum sample was positive for tTG antibodies but negative for EMA. Ten out of 13 positive subjects consented to undergo duodenal biopsy, which invariably produced evidence of CD despite the absence of clinical signs/symptoms. A post-diagnostic clinical investigation provided evidence showing mild iron deficiency (4 subjects) and osteoporosis (2 subjects). After counselling, all subjects accepted a gluten-free diet. CONCLUSIONS: The prevalence of CD in the study group was 1:100 (1.0%; 95% CI: 0.5-1.8%): this indicates that CD is largely underdiagnosed in Carcare. Our results suggest that the low prevalence of CD observed in some regions is likely to be due to underdiagnosis.     

Population screening for coeliac disease in a low prevalence area in Italy

Objective. A screening program was proposed for the village of Carcare (population 5700), located in a region of Italy with an apparently low prevalence of coeliac disease (CD): only 1 patient diagnosed out of 2557 inhabitants. The study group comprised 1002 individuals (568?F, 434?M, age range 13–90 years) recruited from blood donors, secondary school pupils and people referred to the local outpatient facilities for routine blood chemistry. Material and methods. Total IgA, IgA anti-tissue transglutaminase (tTG) (ELISA, recombinant human antigen) and IgA antiendomysium (EMA) (IFI, umbilical cord substrate) antibodies were measured in the serum of all participants. All patients with IgA deficiency were investigated for IgG tTG antibodies, and in the case of disagreement between tTG and EMA, they were typed for HLA DQ2-DQ8 haplotypes. Results. Thirteen subjects were positive and 988 negative for autoantibodies (3/988 had IgA deficiency). One serum sample was positive for tTG antibodies but negative for EMA. Ten out of 13 positive subjects consented to undergo duodenal biopsy, which invariably produced evidence of CD despite the absence of clinical signs/symptoms. A post-diagnostic clinical investigation provided evidence showing mild iron deficiency (4 subjects) and osteoporosis (2 subjects). After counselling, all subjects accepted a gluten-free diet. Conclusions. The prevalence of CD in the study group was 1:100 (1.0%; 95% CI: 0.5–1.8%): this indicates that CD is largely underdiagnosed in Carcare. Our results suggest that the low prevalence of CD observed in some regions is likely to be due to underdiagnosis.     

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.     

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.     

Screening of the adult population in Iran for coeliac disease: comparison of the tissue-transglutaminase antibody and anti-endomysial antibody tests

BACKGROUND AND AIMS: Population-based studies for the prevalence of coeliac disease (CD) in west-Asian countries are scarce. We aimed to determine the prevalence of gluten-sensitive enteropathy (GSE) in the general population of northern and southern Iran, and evaluate the sensitivity and specificity of the anti-endomysial antibody (EMA) immunofluorescent test and the enzyme-linked immunosorbent assay-based test for determination of the IgA anti-tissue transglutaminase antibody (tTG-Ab) using the human recombinant transglutaminase antigen for the detection of CD in screening the asymptomatic adult population. MATERIAL AND METHODS: Using a stratified random sampling method we enrolled a total of 2799 individuals (1438 from Sari and 1361 from Kerman). The mean age was 33.7 years (range 18-66), with 1398 men. IgA anti-tissue transglutaminase (tTG) and IgA anti-EMA were determined in the serum of all subjects. Those participants with a positive serology for any of the two tests underwent small intestinal biopsy, and were classified according to revised Marsh criteria histologically. A diagnosis of GSE was based on positive serology and a compatible histopathological finding. The maximum likelihood latent class model was used to estimate the sensitivity and specificity of the two tests. RESULTS: Twenty-nine cases showed positive IgA tTG-Ab (15 men and 14 women, mean age 35.4 years, range 18-59), whereas only five were simultaneously positive for EMA. Except for two subjects with normal small bowel histology (Marsh 0), all other subjects were found to have biopsy findings compatible with GSE: 18 Marsh I, five Marsh II, three Marsh IIIa and one Marsh IIIc lesions. he prevalence of GSE was 0.96% or 1:104. The sensitivity and specificity of the human-recombinant IgA tTG-Ab assay were 100 and 99%, respectively, whereas the results for IgA EMA were 19 and 100%, respectively. The IgA EMA was positive in cases with advanced mucosal lesions of the small bowel. The mean serum value of IgA tTG-Ab was higher in patients with severe enteropathy compared with those showing slight mucosal changes (P<0.05). CONCLUSION: The minimum prevalence of gluten sensitivity among the general population of northern and southern Iran is 1:104. The best screening test for the detection of GSE in the general population is IgA tTG-Ab.     

Serological screening for coeliac disease in patients with juvenile idiopathic arthritis

Background and study aimsJuvenile idiopathic arthritis (JIA) is characterized by autoimmune aetiology. A gene locus 4q27 related to rheumatoid arthritis, psoriatic arthritis, and coeliac disease is associated with susceptibility to JIA. There are reports indicating several patients with JIA had been diagnosed with CD. We aimed to assess the frequency of coeliac disease (CD) in patients with juvenile idiopathic arthritis (JIA).Patients and methodsThis prospective study was carried out from October 2015 to August 2016 and included 96 patients with JIA. All patients were evaluated in terms of clinical and laboratory findings of CD. Levels of total IgA and tissue transglutaminase antibody (tTG) IgA were measured in all patients. Those with increased level of tTG IgA were further tested for anti-endomysium IgA antibodies (EMA). Gastroduodenoscopy were planned for a definite diagnosis of CD in patients with positive EMA.ResultsOf the 96 patients in our study, 34 (35.4%) had oligoarticular form of JIA, 29 (30.2%) had polyarticular form, 12 (12.5%) had ERA form, 11 (11.5%) had systemic form, and 10 (10.4%) had psoriatic form. Sixteen of our patients (16.6%) were not using any drugs during the study. Neither EMA IgA antibodies were analysed nor gastro-duodenoscopy was performed because no patients were positive for tTG IgA. There was no difference in terms of tTG levels between the patients using NSAIDs or other drugs.ConclusionWe did not find CD in children with JIA. Long term studies with more JIA patients are needed to provide more precise interpretation.     

Antibodies Against Human Tissue Transglutaminase and Endomysium in Diagnosing and Monitoring Coeliac Disease

Background: Coeliac disease (CD) patients often present a variety of uncharacteristic symptoms and therefore sensitive and specific screening tests are needed as an aid in making an accurate diagnosis. A recently developed ELISA, using human recombinant tissue transglutaminase (tTG) as antigen, was evaluated for its significance in the diagnosis of CD. The patient's compliance to a gluten-free diet and the serological reaction during gluten challenge were also monitored. The results were compared with IgA-endomysium antibody (EMA) results. Methods: Sera previously collected from 365 patients (0.4-76 years) with jejunal biopsy on a gluten-containing diet and from 41 patients on a gluten-free diet or challenge were tested for IgA anti-human tTG antibodies (IgA tTG ab) with Celikey ® (Pharmacia Diagnostics). The study population comprised 208 CD patients and 157 controls. The diagnostic performance and cut-off for the assay were estimated with ROC analysis. EMA was analysed by indirect immunofluorescence microscopy on cryostat sections of monkey oesophagus. Results: 200/208 patients with CD had positive IgA tTG ab (median >100 U/ml), while only 1/157 of the control patients were positive (median 1.67 U/ml). The area under the ROC curve was 98.3% and the sensitivity and specificity of the test were 96% and 99% for the study population. Only 4/365 patients (1%) presented discordant IgA tTG ab and EMA results, 2 of them had only IgA tTG ab and 2 only EMA. The IgA tTG ab levels and the EMA titres were closely correlated to the duration of gluten-free diet and gluten challenge, respectively. Conclusion: IgA tTG ab can be used as an accurate observer-independent alternative to EMA in diagnosing or monitoring CD.     

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.     

Antibodies against human tissue transglutaminase and endomysium in diagnosing and monitoring coeliac disease

BACKGROUND: Coeliac disease (CD) patients often present a variety of uncharacteristic symptoms and therefore sensitive and specific screening tests are needed as an aid in making an accurate diagnosis. A recently developed ELISA, using human recombinant tissue transglutaminase (tTG) as antigen, was evaluated for its significance in the diagnosis of CD. The patient's compliance to a gluten-free diet and the serological reaction during gluten challenge were also monitored. The results were compared with IgA-endomysium antibody (EMA) results. METHODS: Sera previously collected from 365 patients (0.4-76 years) with jejunal biopsy on a gluten-containing diet and from 41 patients on a gluten-free diet or challenge were tested for IgA anti-human tTG antibodies (IgA tTG ab) with Celikey (Pharmacia Diagnostics). The study population comprised 208 CD patients and 157 controls. The diagnostic performance and cut-off for the assay were estimated with ROC analysis. EMA was analysed by indirect immunofluorescence microscopy on cryostat sections of monkey oesophagus. RESULTS: 200/208 patients with CD had positive IgA tTG ab (median >100 U/ml), while only 1/157 of the control patients were positive (median 1.67 U/ml). The area under the ROC curve was 98.3% and the sensitivity and specificity of the test were 96% and 99% for the study population. Only 4/365 patients (1%) presented discordant IgA tTG ab and EMA results, 2 of them had only IgA tTG ab and 2 only EMA. The IgA tTG ab levels and the EMA titres were closely correlated to the duration of gluten-free diet and gluten challenge, respectively. CONCLUSION: IgA tTG ab can be used as an accurate observer-independent alternative to EMA in diagnosing or monitoring CD.     

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.     

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.