Objective: To evaluate two commercial stool tests for detection of secretory IgA antibodies against gliadin and human tissue transglutaminase for diagnosis of coeliac disease in children with symptoms. Setting: Tertia...Objective: To evaluate two commercial stool tests for detection of secretory IgA antibodies against gliadin and human tissue transglutaminase for diagnosis of coeliac disease in children with symptoms. Setting: Tertiary care children’s hospital. Participants: Coded stool samples from 20 children with newly diagnosed coeliac disease and 64 controls. Six children with coeliac disease had stool tests every two weeks for three months after starting a gluten-free diet. Main outcome measures: Secretory IgA antibodies against gliadin and human tissue transglutaminase in stool samples, determined in duplicate by using recommended cut-off limits. Results: Sensitivity of faecal antibodies a-gainst human tissue transglutaminase was 10% (95% confidence interval l%to 32% ), and specificity was 98% (91% to 100% ). For antibodies against gliadin, sensitivity was 6% (0% to 29% ) and specificity was 97% (89% to 100% ). Optimisation of cut-off limits by receiver operating characteristic analysis and use of results of both tests increased sensitivity to 82% , but specificity decreased to 58%. All follow-up stool tests remained negative, except for two positive anti-gliadin results in one patient, six and 10 weeks after the gluten-free diet was started. Conclusions: Neither stool test was suitable for screening for coeliac disease in children with symptoms.展开更多
Celiac disease (CD) is a disease having the characteristic pathology of the mu cosa of the small intestine. The prevalence of CD in the Turkish population has not been investigated previously. The present study was de...Celiac disease (CD) is a disease having the characteristic pathology of the mu cosa of the small intestine. The prevalence of CD in the Turkish population has not been investigated previously. The present study was designed to determine th e prevalence of CD in healthy blood donors. Serum samples of 2000 healthy blood donors presenting to Hacettepe University Faculty of Medicine Hospital Blood Ban k were tested for tissue transglutaminase (tTG) IgA and IgG antibodies with enzy me-linked immunosorbent assay (ELISA; Euroimmune, Germany). The histopathologic al findings for the cases with positive serology were evaluated. The distributio n of sex was 95.7%male, and 4.3%female. The mean age was 33±9. Among 2000 don ors, 23 (1.15%) were positive for tTG IgA antibody and 3 (0.15%) were positive for tTG IgG antibody. None of the samples was positive for both antibodies. Ser um total IgA was measured in two cases with only tTG IgG positivity and was foun d to be low in one case. Twelve subjects positive for tTG agreed to endoscopy an d biopsy. Histopathological examination revealed changes classified as Marsh III -II in one,Marsh II in two, Marsh I in seven, and Marsh 0 in two donors. This w as the first study conducted to determine the prevalence of tTG positivity in th e Turkish population. The tTG antibody positivity prevalence in healthy blood do nors was as high as 1.3%. This study shows that the prevalence of CD in the Tur kish population is relatively high in comparison to that in the Western world.展开更多
Objective. In coeliac disease, autoantibodies directed against transglutaminase 2 are produced in small-bowel mucosa, and they have been found to be deposited extracellularly. The aim of this study was to investigate ...Objective. In coeliac disease, autoantibodies directed against transglutaminase 2 are produced in small-bowel mucosa, and they have been found to be deposited extracellularly. The aim of this study was to investigate whether such mucosal IgA deposits are important in the diagnostic work-up of early-stage coeliac disease without small-bowel mucosal villous atrophy. Material and methods. Forty-one adults suspected of coeliac disease owing to increased density of mucosal γδ+intraepithelial lymphocytes but normal villous morphology were randomized to gluten challenge or a gluten-free diet for 6 months. Clinically and histologically verified gluten dependency was compared with existence of small-bowel mucosal transglutaminase 2-specific extracellular IgA deposits and (coeliac disease-type) HLA DQ2 and DQ8; 34 non-coeliac subjects and 18 patients with classical coeliac disease served as controls. Results. Of the 41 patients, 5 in the challenge group and 6 in the gluten-free diet group were clinically gluten sensitive; all 11 had HLA DQ2 or DQ8. Ten of these 11 patients showed transglutaminase 2-targeted mucosal IgA deposits, which were dependent on gluten consumption. Minimal IgA deposits were seen in only 3 out of 30 patients with suspected coeliac disease without any clinically detected gluten dependency. The deposits were found in all classical coeliac patients and in none of the non-coeliac control subjects. Conclusions. Clinically pertinent coeliac disease exists despite normal small-bowel mucosal villous architecture. Mucosal transglutaminase 2-specific IgA deposits can be utilized in detecting such patients with genetic gluten intolerance.展开更多
Objective:To evaluate two commercial stool tests for detection of secretory IgA antibodies against gliadin and human tissue transglutaminase for diagnosis of coeliac disease in children with symptoms.Setting:Tertiary ...Objective:To evaluate two commercial stool tests for detection of secretory IgA antibodies against gliadin and human tissue transglutaminase for diagnosis of coeliac disease in children with symptoms.Setting:Tertiary care children’s hospital.Participants:Coded stool samples from 20 children with newly diagnosed coeliac disease and 64 controls.Six children with coeliac disease had stool tests every two weeks for three months after starting a gluten-free diet.Main outcome measures:Secretory IgA antibodies against gliadin and human tissue transglutaminase in stool samples,determined in duplicate by using recommended cut-off limits.Results:Sensitivity of faecal antibodies against human tissue transglutaminase was 10%(95%confidence interval 1%to 32%),and specificity was 98%(91%to 100%).For antibodies against gliadin,sensitivity was 6%(0%to 29%)and specificity was 97%(89%to 100%).Optimisation of cut-off limits by receiver operating characteristic analysis and use of results of both tests increased sensitivity to 82%,but specificity decreased to 58%.All follow-up stool tests remained negative,except for two positive anti-gliadin results in one patient,six and 10 weeks after the gluten-free diet was started.Conclusions:Neither stool test was suitable for screening for coeliac disease in children with symptoms.展开更多
Although the specific IgA autoantibody responsible for the pathogenesis of dermatitis herpetiformis (DH) is unknown, the presence of IgA is considered essential in the pathogenesis of DH. To date, no cases of IgA defi...Although the specific IgA autoantibody responsible for the pathogenesis of dermatitis herpetiformis (DH) is unknown, the presence of IgA is considered essential in the pathogenesis of DH. To date, no cases of IgA deficiency have been reported in DH. In contrast, IgA deficiency is found in 2% to 3% of patients with celiac disease, a rate 10 to 15 times higher than the normal population. We report 2 patients with DH who also have partial IgA deficiency. We evaluated the sera of these patients for the presence of IgA autoantibodies to endomysium,tissue transglutaminase, epidermal transglutaminase, and gliadin. Both patients were found to have IgA endomysial and tissue transglutaminase antibodies, and serologic markers for DH. Corresponding IgG autoantibodies were not useful serologicmarkers of DH in the setting of IgA deficiency, as they often are in celiac disease. We then screened 98 DH sera for total IgA levels and identified 1 additional case with IgA deficiency. In conclusion, DH may develop in patients with partial IgA deficiency, indicating that pathogenically directed IgA antibodies are likely sufficient for cutaneous IgA deposition in this disease.展开更多
Objective. A slight to moderate increase in autoantibodies to transglutaminase 2 (TG2), but no morphological evidence of villous atrophy to confirm the diagnosis of celiac disease (CD) poses a challenge for clinicians...Objective. A slight to moderate increase in autoantibodies to transglutaminase 2 (TG2), but no morphological evidence of villous atrophy to confirm the diagnosis of celiac disease (CD) poses a challenge for clinicians. Our aim was to study thematrix metalloproteinase (MMP) profile, proliferative and apoptotic characteristics of jejunal biopsies obtained from such pediatric patients in order to find markers predictive of early changes in extracellular matrix degrading enzymes in the development of CD. Material and methods. Twenty-eight children with positive screening tests (increase in transglutaminase and/or endomysium antibodies), but minor histological changes in the gut (Marsh grade 0-2), were studied and followed up for 2-3 years. In situ hybridizations for MMP-1, -3 and -12 were performed and sections were immunostained for MMP-19 and -26. Proliferating cells were identified by Ki-67 immunostaining and apoptotic cells using the TUNEL technique. Results. MMP-12 was detected in macrophages in 16/28 samples and its expression was associated with increased autoantibodies for TG2 and densities of CD3 and gammadelta positive T-cells in the epithelium. The number of stromal MMP-26 positive cells was high in patients with high TG2 titers. Expression of MMP-12, MMP-1 and -3 clustered in children with type 1 diabetes (T1D) and the proportion of apoptotic mucosal cells was increased in patients with T1D compared to the others. When children with CD were compared to those who did not develop it, the numbers of IEL, cryptal Ki-67, CD-3, and MMP-12 positive cells were higher and showed the most significant differences. Conclusions. In pediatric patients, increased numbers of MMP-12 positive macrophages in lamina propria associate with high titers of antibodies to TG2 and proness to CD. A stage of mild inflammation may contribute to the upregulation of MMPs in the gut of patients with T1D.展开更多
文摘Objective: To evaluate two commercial stool tests for detection of secretory IgA antibodies against gliadin and human tissue transglutaminase for diagnosis of coeliac disease in children with symptoms. Setting: Tertiary care children’s hospital. Participants: Coded stool samples from 20 children with newly diagnosed coeliac disease and 64 controls. Six children with coeliac disease had stool tests every two weeks for three months after starting a gluten-free diet. Main outcome measures: Secretory IgA antibodies against gliadin and human tissue transglutaminase in stool samples, determined in duplicate by using recommended cut-off limits. Results: Sensitivity of faecal antibodies a-gainst human tissue transglutaminase was 10% (95% confidence interval l%to 32% ), and specificity was 98% (91% to 100% ). For antibodies against gliadin, sensitivity was 6% (0% to 29% ) and specificity was 97% (89% to 100% ). Optimisation of cut-off limits by receiver operating characteristic analysis and use of results of both tests increased sensitivity to 82% , but specificity decreased to 58%. All follow-up stool tests remained negative, except for two positive anti-gliadin results in one patient, six and 10 weeks after the gluten-free diet was started. Conclusions: Neither stool test was suitable for screening for coeliac disease in children with symptoms.
文摘Celiac disease (CD) is a disease having the characteristic pathology of the mu cosa of the small intestine. The prevalence of CD in the Turkish population has not been investigated previously. The present study was designed to determine th e prevalence of CD in healthy blood donors. Serum samples of 2000 healthy blood donors presenting to Hacettepe University Faculty of Medicine Hospital Blood Ban k were tested for tissue transglutaminase (tTG) IgA and IgG antibodies with enzy me-linked immunosorbent assay (ELISA; Euroimmune, Germany). The histopathologic al findings for the cases with positive serology were evaluated. The distributio n of sex was 95.7%male, and 4.3%female. The mean age was 33±9. Among 2000 don ors, 23 (1.15%) were positive for tTG IgA antibody and 3 (0.15%) were positive for tTG IgG antibody. None of the samples was positive for both antibodies. Ser um total IgA was measured in two cases with only tTG IgG positivity and was foun d to be low in one case. Twelve subjects positive for tTG agreed to endoscopy an d biopsy. Histopathological examination revealed changes classified as Marsh III -II in one,Marsh II in two, Marsh I in seven, and Marsh 0 in two donors. This w as the first study conducted to determine the prevalence of tTG positivity in th e Turkish population. The tTG antibody positivity prevalence in healthy blood do nors was as high as 1.3%. This study shows that the prevalence of CD in the Tur kish population is relatively high in comparison to that in the Western world.
文摘Objective. In coeliac disease, autoantibodies directed against transglutaminase 2 are produced in small-bowel mucosa, and they have been found to be deposited extracellularly. The aim of this study was to investigate whether such mucosal IgA deposits are important in the diagnostic work-up of early-stage coeliac disease without small-bowel mucosal villous atrophy. Material and methods. Forty-one adults suspected of coeliac disease owing to increased density of mucosal γδ+intraepithelial lymphocytes but normal villous morphology were randomized to gluten challenge or a gluten-free diet for 6 months. Clinically and histologically verified gluten dependency was compared with existence of small-bowel mucosal transglutaminase 2-specific extracellular IgA deposits and (coeliac disease-type) HLA DQ2 and DQ8; 34 non-coeliac subjects and 18 patients with classical coeliac disease served as controls. Results. Of the 41 patients, 5 in the challenge group and 6 in the gluten-free diet group were clinically gluten sensitive; all 11 had HLA DQ2 or DQ8. Ten of these 11 patients showed transglutaminase 2-targeted mucosal IgA deposits, which were dependent on gluten consumption. Minimal IgA deposits were seen in only 3 out of 30 patients with suspected coeliac disease without any clinically detected gluten dependency. The deposits were found in all classical coeliac patients and in none of the non-coeliac control subjects. Conclusions. Clinically pertinent coeliac disease exists despite normal small-bowel mucosal villous architecture. Mucosal transglutaminase 2-specific IgA deposits can be utilized in detecting such patients with genetic gluten intolerance.
文摘Objective:To evaluate two commercial stool tests for detection of secretory IgA antibodies against gliadin and human tissue transglutaminase for diagnosis of coeliac disease in children with symptoms.Setting:Tertiary care children’s hospital.Participants:Coded stool samples from 20 children with newly diagnosed coeliac disease and 64 controls.Six children with coeliac disease had stool tests every two weeks for three months after starting a gluten-free diet.Main outcome measures:Secretory IgA antibodies against gliadin and human tissue transglutaminase in stool samples,determined in duplicate by using recommended cut-off limits.Results:Sensitivity of faecal antibodies against human tissue transglutaminase was 10%(95%confidence interval 1%to 32%),and specificity was 98%(91%to 100%).For antibodies against gliadin,sensitivity was 6%(0%to 29%)and specificity was 97%(89%to 100%).Optimisation of cut-off limits by receiver operating characteristic analysis and use of results of both tests increased sensitivity to 82%,but specificity decreased to 58%.All follow-up stool tests remained negative,except for two positive anti-gliadin results in one patient,six and 10 weeks after the gluten-free diet was started.Conclusions:Neither stool test was suitable for screening for coeliac disease in children with symptoms.
文摘Although the specific IgA autoantibody responsible for the pathogenesis of dermatitis herpetiformis (DH) is unknown, the presence of IgA is considered essential in the pathogenesis of DH. To date, no cases of IgA deficiency have been reported in DH. In contrast, IgA deficiency is found in 2% to 3% of patients with celiac disease, a rate 10 to 15 times higher than the normal population. We report 2 patients with DH who also have partial IgA deficiency. We evaluated the sera of these patients for the presence of IgA autoantibodies to endomysium,tissue transglutaminase, epidermal transglutaminase, and gliadin. Both patients were found to have IgA endomysial and tissue transglutaminase antibodies, and serologic markers for DH. Corresponding IgG autoantibodies were not useful serologicmarkers of DH in the setting of IgA deficiency, as they often are in celiac disease. We then screened 98 DH sera for total IgA levels and identified 1 additional case with IgA deficiency. In conclusion, DH may develop in patients with partial IgA deficiency, indicating that pathogenically directed IgA antibodies are likely sufficient for cutaneous IgA deposition in this disease.
文摘Objective. A slight to moderate increase in autoantibodies to transglutaminase 2 (TG2), but no morphological evidence of villous atrophy to confirm the diagnosis of celiac disease (CD) poses a challenge for clinicians. Our aim was to study thematrix metalloproteinase (MMP) profile, proliferative and apoptotic characteristics of jejunal biopsies obtained from such pediatric patients in order to find markers predictive of early changes in extracellular matrix degrading enzymes in the development of CD. Material and methods. Twenty-eight children with positive screening tests (increase in transglutaminase and/or endomysium antibodies), but minor histological changes in the gut (Marsh grade 0-2), were studied and followed up for 2-3 years. In situ hybridizations for MMP-1, -3 and -12 were performed and sections were immunostained for MMP-19 and -26. Proliferating cells were identified by Ki-67 immunostaining and apoptotic cells using the TUNEL technique. Results. MMP-12 was detected in macrophages in 16/28 samples and its expression was associated with increased autoantibodies for TG2 and densities of CD3 and gammadelta positive T-cells in the epithelium. The number of stromal MMP-26 positive cells was high in patients with high TG2 titers. Expression of MMP-12, MMP-1 and -3 clustered in children with type 1 diabetes (T1D) and the proportion of apoptotic mucosal cells was increased in patients with T1D compared to the others. When children with CD were compared to those who did not develop it, the numbers of IEL, cryptal Ki-67, CD-3, and MMP-12 positive cells were higher and showed the most significant differences. Conclusions. In pediatric patients, increased numbers of MMP-12 positive macrophages in lamina propria associate with high titers of antibodies to TG2 and proness to CD. A stage of mild inflammation may contribute to the upregulation of MMPs in the gut of patients with T1D.
