AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(...AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2 b anti-TF monoclonal antibody 1849(anti-TF 1849) to a NIR photosensitizer,ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PITinduced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIRPIT, tumor-bearing mice were separated into 5 groups:(1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure(50 J/cm2) on two consecutive days(Days 1 and 2);(2) NIR light exposure(50 J/cm2) only on two consecutive days(Days 1 and 2);(3) 100 μg of 1849-ICG i.v. administration;(4) 100 μg of unlabeled antiTF 1849 i.v. administration; and(5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical(IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments. RESULTS High TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for 27 d after the treatment start date [2.83 ± 0.38(NIR-PIT) vs 5.42 ± 1.61(Untreated), vs 4.90 ± 0.87(NIR), vs 4.28 ±1.87(1849-ICG), vs 4.35 ± 1.42(anti-TF 1849), at Day 27, P < 0.05]. Tumors that received NIR-PIT showed evidence of necrotic cell death-associated features upon hematoxylin-eosin staining accompanied by a decrease in Ki-67-positive cells(a cell proliferation marker) by IHC examination.CONCLUSION The TF-targeted NIR-PIT with the 1849-ICG conjugate can potentially open a new platform for treatment of TF-expressing pancreatic cancer.展开更多
Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with ...Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.展开更多
AIM: To determine the prevalence of gluten sensitive enteropathy (GSE) in a large group of patients with iron deficiency anemia (IDA) of obscure origin. METHODS: In this cross-sectional study, patients with IDA of obs...AIM: To determine the prevalence of gluten sensitive enteropathy (GSE) in a large group of patients with iron deficiency anemia (IDA) of obscure origin. METHODS: In this cross-sectional study, patients with IDA of obscure origin were screened for GSE. Anti- endomysial antibody (EMA) and tissue transglutamin- ase antibody (tTG) levels were evaluated and duodenal biopsies were taken and scored according to the Marsh classification. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histol- ogy. Gluten free diet (GFD) was advised for all the GSE patients. RESULTS: Of the 4120 IDA patients referred to our Hematology departments, 206 (95 male) patients were found to have IDA of obscure origin. Thirty out of 206 patients (14.6%) had GSE. The mean age of GSE pa- tients was 34.6 ± 17.03 (range 10-72 years). The female to male ratio was 1.3:1. Sixteen patients had Marsh 3,12 had Marsh 2, and 2 had Marsh 1 lesions. The sever- ity of anemia was in parallel with the severity of duode- nal lesions. Twenty-two GSE patients (73.3%) had no gastrointestinal symptoms. Fourteen GSE patients who adhered to GFD without receiving iron supplementation agreed to undergo follow up visits. After 6 mo of GFD, their mean hemoglobin levels (Hb) increased from 9.9 ± 1.6 to 12.8 ± 1.0 g/dL (P < 0.01). Interestingly, in 6 out of 14 patients who had Marsh 1/2 lesions (e.g. no villous atrophy) on duodenal biopsy, mean Hb increased from 11.0 ± 1.1 to 13.1 ± 1.0 g/dL (P < 0.01) while they did not receive any iron supplementation. CONCLUSION: There is a high prevalence (e.g. 14.6%) of GSE in patients with IDA of obscure origin. Gluten free diet can improve anemia in GSE patients who have mild duodenal lesions without villous atrophy.展开更多
AIM:To estimate the prevalence of celiac disease(CD) in adult patients with presumed irritable bowel syndrome(IBS) .METHODS:Between March 2005 and December 2008,742 consecutive patients(293 male,median age 43 years,ra...AIM:To estimate the prevalence of celiac disease(CD) in adult patients with presumed irritable bowel syndrome(IBS) .METHODS:Between March 2005 and December 2008,742 consecutive patients(293 male,median age 43 years,range 18-69 years) fulfilling the Rome Ⅱ criteria for IBS were prospectively enrolled in the study.IBS was diagnosed via self-completed Rome Ⅱ modular questionnaires.Anti-tissue transglutaminase(anti-tTG) serology was checked to initially recognize possible CD cases.Patients with a positive test were offered endoscopic duodenal biopsy to confirm the diagnosis of CD.RESULTS:Thirty two patients(15 male,median age 41 years,range 19-59 years) were found to have organic diseases other than CD.Twenty four patients tested positive for anti-tTG antibodies,and duodenal biopsies confirmed the diagnosis in all of them.Thus,in this patient population with presumed IBS,3.23% actually had CD.CONCLUSION:CD is common in patients with presumed IBS.Routine screening for CD in patients with symptoms of IBS is recommended.展开更多
AIM:To investigate whether celiac disease(CD)patients with tissue-transglutaminase antibody(tTGA)≥100 U/mL are different from patients with lower tTGA levels.METHODS:Biopsy-proven(MarshⅢ)pediatric CD patients(n=116)...AIM:To investigate whether celiac disease(CD)patients with tissue-transglutaminase antibody(tTGA)≥100 U/mL are different from patients with lower tTGA levels.METHODS:Biopsy-proven(MarshⅢ)pediatric CD patients(n=116)were prospectively included between March 2009 and October 2012.The biopsies were evaluated by a single pathologist who was blinded to all of the patients’clinical data.The patients were distributed into 2 groups according to their tTGA level,which was measured using enzyme-linked immunoassay:tTGA≥100 U/mL and Ttga<100 U/mL.The patients’characteristics,symptoms,human leukocyte antigen(HLA)genotype and degree of histological involvement were compared between the 2 groups.RESULTS:A total of 34(29.3%)children had tTGA values<100 U/mL and 82(70.7%)tTGA levels of≥100 U/mL.Patients with high tTGA levels had lower average body weight-for-height standard deviation scores(SDS)than did patients with tTGA<100 U/mL(-0.20±1.19 SDS vs 0.23±1.03 SDS,P=0.025).In the low tTGA group,gastrointestinal symptoms were more common(97.1%vs 75.6%,P=0.006).More specifically,abdominal pain(76.5%vs 51.2%;P=0.012)and nausea(17.6%vs 3.7%,P=0.018)were more frequent among patients with low tTGA.In contrast,patients with solely extraintestinal manifestations were only present in the high tTGA group(18.3%,P=0.005).These patients more commonly presented with aphthous stomatitis(15.9%vs 0.0%,P=0.010)and anemia(32.9%vs 11.8%,P=0.019).In addition,when evaluating the number of CD-associated HLA-DQ heterodimers(HLA-DQ2.5,HLA-DQ2.2 and HLA-DQ8),patients with low tTGA levels more commonly had only1 disease-associated heterodimer(61.8%vs 31.7%,P=0.005),while patients with high tTGA more commonly had multiple heterodimers.Finally,patients with tTGA≥100 U/mL more often had a MarshⅢc lesion(73.2%vs 20.6%,P≤0.001)while in patients with low tTGA patchy lesions were more common(42.4%vs6.8%,P≤0.001).CONCLUSION:Patients with tTGA≥100 U/mL show several signs of more advanced disease.They also carry a larger number of CD associated HLA-DQ heterodimers.展开更多
AIM:To study the coincidence of celiac disease, we tested its serological markers in patients with various liver diseases.METHODS:Large-scale screening of serum antibodies against tissue transglutaminase (tTG), and de...AIM:To study the coincidence of celiac disease, we tested its serological markers in patients with various liver diseases.METHODS:Large-scale screening of serum antibodies against tissue transglutaminase (tTG), and deamidated gliadin using enzyme-linked immunosorbent assay and serum antibodies against endomysium using immunohistochemistry, in patients with various liver diseases (n = 962) and patients who underwent liver transplantation (OLTx, n = 523) was performed. The expression of tTG in liver tissue samples of patients simultaneously suffering from celiac disease and from various liver diseases using immunohistochemistry was carried out. The final diagnosis of celiac disease was confirmed by histological analysis of small-intestinal biopsy. RESULTS:We found that 29 of 962 patients (3%) with liver diseases and 5 of 523 patients (0.8%) who underwent OLTx were seropositive for IgA and IgG anti-tTG antibodies. However, celiac disease was biopsy-diagnosed in 16 patients:4 with autoimmune hepatitis type Ⅰ, 3 with Wilson's disease, 3 with celiac hepatitis, 2 with primary sclerosing cholangitis, 1 with primary biliary cirrhosis, 1 with Budd-Chiari syndrome, 1 with toxic hepatitis, and 1 with non-alcoholic steatohepatitis. Unexpectedly, the highest prevalence of celiac disease was found in patients with Wilson's disease (9.7%), with which it is only rarely associated. On the other hand, no OLTx patients were diagnosed with celiac disease in our study. A pilot study of the expression of tTG in liver tissue using immunohistochemistry documented the overexpression of this molecule in endothelial cells and periportal hepatocytes of patients simultaneously suffering from celiac disease and toxic hepatitis, primary sclerosing cholangitis or autoimmune hepatitis type Ⅰ. CONCLUSION:We suggest that screening for celiac disease may be beneficial not only in patients with associated liver diseases, but also in patients with Wilson's disease.展开更多
BACKGROUND Celiac disease(CD)is an immune-mediated enteropathy that is primarily treated with a gluten-free diet(GFD).Mucosal healing is the main target of the therapy.Currently,duodenal biopsy is the only way to eval...BACKGROUND Celiac disease(CD)is an immune-mediated enteropathy that is primarily treated with a gluten-free diet(GFD).Mucosal healing is the main target of the therapy.Currently,duodenal biopsy is the only way to evaluate mucosal healing,and noninvasive markers are challenging.Persistent elevation of anti-tissue transglutaminase antibodies(aTTG)is not an ideal predictor of persistent villous atrophy(VA).Data regarding prediction of atrophy using anti-deamidated gliadin peptide antibodies(aDGP)and abdominal ultrasonography are lacking.AIM To evaluate the ability of aTTG,aDGP,small bowel ultrasonography,and clinical and laboratory parameters in predicting persistent VA determined using histology.METHODS Patients with CD at least 1 year on a GFD and available follow-up duodenal biopsy,levels of aTTG and aDGP,and underwent small bowel ultrasonography were included in this retrospective cohort study.We evaluated the sensitivity,specificity,and positive and negative predictive values of aTTG,aDGP,small bowel ultrasonography,laboratory and clinical parameters to predict persistent VA.A receiver operating characteristic(ROC)curve analysis of antibody levels was used to calculate cut off values with the highest accuracy for atrophy prediction.RESULTS Complete data were available for 82 patients who were followed up over a period of four years(2014-2018).Among patients included in the analysis,women(67,81.7%)were predominant and the mean age at diagnosis was 33.8 years.Followup biopsy revealed persistent VA in 19 patients(23.2%).The sensitivity and specificity of aTTG using the manufacturer’s diagnostic cutoff value to predict atrophy was 50%and 85.7%,respectively,while the sensitivity and specificity of aDGP(using the diagnostic cutoff value)was 77.8%and 75%,respectively.Calculation of an optimal cutoff value using ROC analysis(13.4 U/mL for aTTG IgA and 22.6 U/mL for aDGP IgA)increased the accuracy and reached 72.2%[95%confidence interval(CI):46.5-90.3]sensitivity and 90%(95%CI:79.5-96.2)specificity for aDGP IgA and 66.7%(95%CI:41.0-86.7)sensitivity and 93.7%(95%CI:84.5-98.2)specificity for aTTG IgA.The sensitivity and specificity of small bowel ultrasonography was 64.7%and 73.5%,respectively.A combination of serology with ultrasound imaging to predict persistent atrophy increased the positive predictive value and specificity to 88.9%and 98%for aTTG IgA and to 90.0%and 97.8%for aDGP IgA.Laboratory and clinical parameters had poor predictive values.CONCLUSION The sensitivity,specificity,and negative predictive value of aTTG and aDGP for predicting persistent VA improved by calculating the best cutoff values.The combination of serology and experienced bowel ultrasound examination may achieve better accuracy for the detection of atrophy.展开更多
AIM To determine dynamic thiol/disulphide homeostasis in celiac disease and to examine the associate with celiac autoantibodies and gluten-free diet.METHODS Seventy three patients with celiac disease and 73 healthy vo...AIM To determine dynamic thiol/disulphide homeostasis in celiac disease and to examine the associate with celiac autoantibodies and gluten-free diet.METHODS Seventy three patients with celiac disease and 73 healthy volunteers were enrolled in the study. In both groups, thiol/disulphide homeostasis was examined with a new colorimetric method recently developed by Erel and Neselioglu. RESULTS In patients with celiac disease, native thiol(P = 0.027) and total thiol(P = 0.031) levels were lower, while disulphide(P < 0.001) level, disulphide/native thiol(P < 0.001) and disulphide/total thiol(P < 0.001) ratios were higher compared to the control group. In patients who do not comply with a gluten-free diet, disulphide/native thiol ratio was found higher compared to the patients who comply with the diet(P < 0.001). In patients withany autoantibody-positive, disulphide/native thiol ratio was observed higher compared to the patients with autoantibody-negative(P < 0.05). It is found that there is a negative correlation between celiac autoantibodies, and native thiol, total thiol levels and native thiol/total thiol ratio, while a positive correlation is observed between disulphide, disulphide/native thiol and disulphide/total thiol levels.CONCLUSION This study is first in the literature which found that the patients with celiac disease the dynamic thiol/disulphide balance shifts through disulphide form compared to the control group.展开更多
基金Supported by a Grant-in-Aid for Scientific Research(C)from the Ministry of Education,Culture,Sports,Science,and Technology,Japan,No.17K10460(to Aung W)
文摘AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2 b anti-TF monoclonal antibody 1849(anti-TF 1849) to a NIR photosensitizer,ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PITinduced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIRPIT, tumor-bearing mice were separated into 5 groups:(1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure(50 J/cm2) on two consecutive days(Days 1 and 2);(2) NIR light exposure(50 J/cm2) only on two consecutive days(Days 1 and 2);(3) 100 μg of 1849-ICG i.v. administration;(4) 100 μg of unlabeled antiTF 1849 i.v. administration; and(5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical(IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments. RESULTS High TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for 27 d after the treatment start date [2.83 ± 0.38(NIR-PIT) vs 5.42 ± 1.61(Untreated), vs 4.90 ± 0.87(NIR), vs 4.28 ±1.87(1849-ICG), vs 4.35 ± 1.42(anti-TF 1849), at Day 27, P < 0.05]. Tumors that received NIR-PIT showed evidence of necrotic cell death-associated features upon hematoxylin-eosin staining accompanied by a decrease in Ki-67-positive cells(a cell proliferation marker) by IHC examination.CONCLUSION The TF-targeted NIR-PIT with the 1849-ICG conjugate can potentially open a new platform for treatment of TF-expressing pancreatic cancer.
基金Supported by The European Union-NextGenerationEU,Through The National Recov-ery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008。
文摘Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.
基金Supported by Local funds from Digestive Disease Research Centre, University of Tehran and Gastrointestinal and Liver Disease Research Centre, Iran University of Medical Science
文摘AIM: To determine the prevalence of gluten sensitive enteropathy (GSE) in a large group of patients with iron deficiency anemia (IDA) of obscure origin. METHODS: In this cross-sectional study, patients with IDA of obscure origin were screened for GSE. Anti- endomysial antibody (EMA) and tissue transglutamin- ase antibody (tTG) levels were evaluated and duodenal biopsies were taken and scored according to the Marsh classification. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histol- ogy. Gluten free diet (GFD) was advised for all the GSE patients. RESULTS: Of the 4120 IDA patients referred to our Hematology departments, 206 (95 male) patients were found to have IDA of obscure origin. Thirty out of 206 patients (14.6%) had GSE. The mean age of GSE pa- tients was 34.6 ± 17.03 (range 10-72 years). The female to male ratio was 1.3:1. Sixteen patients had Marsh 3,12 had Marsh 2, and 2 had Marsh 1 lesions. The sever- ity of anemia was in parallel with the severity of duode- nal lesions. Twenty-two GSE patients (73.3%) had no gastrointestinal symptoms. Fourteen GSE patients who adhered to GFD without receiving iron supplementation agreed to undergo follow up visits. After 6 mo of GFD, their mean hemoglobin levels (Hb) increased from 9.9 ± 1.6 to 12.8 ± 1.0 g/dL (P < 0.01). Interestingly, in 6 out of 14 patients who had Marsh 1/2 lesions (e.g. no villous atrophy) on duodenal biopsy, mean Hb increased from 11.0 ± 1.1 to 13.1 ± 1.0 g/dL (P < 0.01) while they did not receive any iron supplementation. CONCLUSION: There is a high prevalence (e.g. 14.6%) of GSE in patients with IDA of obscure origin. Gluten free diet can improve anemia in GSE patients who have mild duodenal lesions without villous atrophy.
文摘AIM:To estimate the prevalence of celiac disease(CD) in adult patients with presumed irritable bowel syndrome(IBS) .METHODS:Between March 2005 and December 2008,742 consecutive patients(293 male,median age 43 years,range 18-69 years) fulfilling the Rome Ⅱ criteria for IBS were prospectively enrolled in the study.IBS was diagnosed via self-completed Rome Ⅱ modular questionnaires.Anti-tissue transglutaminase(anti-tTG) serology was checked to initially recognize possible CD cases.Patients with a positive test were offered endoscopic duodenal biopsy to confirm the diagnosis of CD.RESULTS:Thirty two patients(15 male,median age 41 years,range 19-59 years) were found to have organic diseases other than CD.Twenty four patients tested positive for anti-tTG antibodies,and duodenal biopsies confirmed the diagnosis in all of them.Thus,in this patient population with presumed IBS,3.23% actually had CD.CONCLUSION:CD is common in patients with presumed IBS.Routine screening for CD in patients with symptoms of IBS is recommended.
文摘AIM:To investigate whether celiac disease(CD)patients with tissue-transglutaminase antibody(tTGA)≥100 U/mL are different from patients with lower tTGA levels.METHODS:Biopsy-proven(MarshⅢ)pediatric CD patients(n=116)were prospectively included between March 2009 and October 2012.The biopsies were evaluated by a single pathologist who was blinded to all of the patients’clinical data.The patients were distributed into 2 groups according to their tTGA level,which was measured using enzyme-linked immunoassay:tTGA≥100 U/mL and Ttga<100 U/mL.The patients’characteristics,symptoms,human leukocyte antigen(HLA)genotype and degree of histological involvement were compared between the 2 groups.RESULTS:A total of 34(29.3%)children had tTGA values<100 U/mL and 82(70.7%)tTGA levels of≥100 U/mL.Patients with high tTGA levels had lower average body weight-for-height standard deviation scores(SDS)than did patients with tTGA<100 U/mL(-0.20±1.19 SDS vs 0.23±1.03 SDS,P=0.025).In the low tTGA group,gastrointestinal symptoms were more common(97.1%vs 75.6%,P=0.006).More specifically,abdominal pain(76.5%vs 51.2%;P=0.012)and nausea(17.6%vs 3.7%,P=0.018)were more frequent among patients with low tTGA.In contrast,patients with solely extraintestinal manifestations were only present in the high tTGA group(18.3%,P=0.005).These patients more commonly presented with aphthous stomatitis(15.9%vs 0.0%,P=0.010)and anemia(32.9%vs 11.8%,P=0.019).In addition,when evaluating the number of CD-associated HLA-DQ heterodimers(HLA-DQ2.5,HLA-DQ2.2 and HLA-DQ8),patients with low tTGA levels more commonly had only1 disease-associated heterodimer(61.8%vs 31.7%,P=0.005),while patients with high tTGA more commonly had multiple heterodimers.Finally,patients with tTGA≥100 U/mL more often had a MarshⅢc lesion(73.2%vs 20.6%,P≤0.001)while in patients with low tTGA patchy lesions were more common(42.4%vs6.8%,P≤0.001).CONCLUSION:Patients with tTGA≥100 U/mL show several signs of more advanced disease.They also carry a larger number of CD associated HLA-DQ heterodimers.
基金Supported by Grant from the Czech Ministry of Health,No. NS9705-4/2008the Academy of Sciences of the Czech Republic, No. A500200709+1 种基金the Czech Science Foundation,No. 310/07/0414Institutional Research Concept Grant, No.AV0Z50200510 and No. RVO: 61388971
文摘AIM:To study the coincidence of celiac disease, we tested its serological markers in patients with various liver diseases.METHODS:Large-scale screening of serum antibodies against tissue transglutaminase (tTG), and deamidated gliadin using enzyme-linked immunosorbent assay and serum antibodies against endomysium using immunohistochemistry, in patients with various liver diseases (n = 962) and patients who underwent liver transplantation (OLTx, n = 523) was performed. The expression of tTG in liver tissue samples of patients simultaneously suffering from celiac disease and from various liver diseases using immunohistochemistry was carried out. The final diagnosis of celiac disease was confirmed by histological analysis of small-intestinal biopsy. RESULTS:We found that 29 of 962 patients (3%) with liver diseases and 5 of 523 patients (0.8%) who underwent OLTx were seropositive for IgA and IgG anti-tTG antibodies. However, celiac disease was biopsy-diagnosed in 16 patients:4 with autoimmune hepatitis type Ⅰ, 3 with Wilson's disease, 3 with celiac hepatitis, 2 with primary sclerosing cholangitis, 1 with primary biliary cirrhosis, 1 with Budd-Chiari syndrome, 1 with toxic hepatitis, and 1 with non-alcoholic steatohepatitis. Unexpectedly, the highest prevalence of celiac disease was found in patients with Wilson's disease (9.7%), with which it is only rarely associated. On the other hand, no OLTx patients were diagnosed with celiac disease in our study. A pilot study of the expression of tTG in liver tissue using immunohistochemistry documented the overexpression of this molecule in endothelial cells and periportal hepatocytes of patients simultaneously suffering from celiac disease and toxic hepatitis, primary sclerosing cholangitis or autoimmune hepatitis type Ⅰ. CONCLUSION:We suggest that screening for celiac disease may be beneficial not only in patients with associated liver diseases, but also in patients with Wilson's disease.
基金Ministry of Health,Czech Republic–conceptual development of research organization,No.FNBr,65269705.
文摘BACKGROUND Celiac disease(CD)is an immune-mediated enteropathy that is primarily treated with a gluten-free diet(GFD).Mucosal healing is the main target of the therapy.Currently,duodenal biopsy is the only way to evaluate mucosal healing,and noninvasive markers are challenging.Persistent elevation of anti-tissue transglutaminase antibodies(aTTG)is not an ideal predictor of persistent villous atrophy(VA).Data regarding prediction of atrophy using anti-deamidated gliadin peptide antibodies(aDGP)and abdominal ultrasonography are lacking.AIM To evaluate the ability of aTTG,aDGP,small bowel ultrasonography,and clinical and laboratory parameters in predicting persistent VA determined using histology.METHODS Patients with CD at least 1 year on a GFD and available follow-up duodenal biopsy,levels of aTTG and aDGP,and underwent small bowel ultrasonography were included in this retrospective cohort study.We evaluated the sensitivity,specificity,and positive and negative predictive values of aTTG,aDGP,small bowel ultrasonography,laboratory and clinical parameters to predict persistent VA.A receiver operating characteristic(ROC)curve analysis of antibody levels was used to calculate cut off values with the highest accuracy for atrophy prediction.RESULTS Complete data were available for 82 patients who were followed up over a period of four years(2014-2018).Among patients included in the analysis,women(67,81.7%)were predominant and the mean age at diagnosis was 33.8 years.Followup biopsy revealed persistent VA in 19 patients(23.2%).The sensitivity and specificity of aTTG using the manufacturer’s diagnostic cutoff value to predict atrophy was 50%and 85.7%,respectively,while the sensitivity and specificity of aDGP(using the diagnostic cutoff value)was 77.8%and 75%,respectively.Calculation of an optimal cutoff value using ROC analysis(13.4 U/mL for aTTG IgA and 22.6 U/mL for aDGP IgA)increased the accuracy and reached 72.2%[95%confidence interval(CI):46.5-90.3]sensitivity and 90%(95%CI:79.5-96.2)specificity for aDGP IgA and 66.7%(95%CI:41.0-86.7)sensitivity and 93.7%(95%CI:84.5-98.2)specificity for aTTG IgA.The sensitivity and specificity of small bowel ultrasonography was 64.7%and 73.5%,respectively.A combination of serology with ultrasound imaging to predict persistent atrophy increased the positive predictive value and specificity to 88.9%and 98%for aTTG IgA and to 90.0%and 97.8%for aDGP IgA.Laboratory and clinical parameters had poor predictive values.CONCLUSION The sensitivity,specificity,and negative predictive value of aTTG and aDGP for predicting persistent VA improved by calculating the best cutoff values.The combination of serology and experienced bowel ultrasound examination may achieve better accuracy for the detection of atrophy.
文摘AIM To determine dynamic thiol/disulphide homeostasis in celiac disease and to examine the associate with celiac autoantibodies and gluten-free diet.METHODS Seventy three patients with celiac disease and 73 healthy volunteers were enrolled in the study. In both groups, thiol/disulphide homeostasis was examined with a new colorimetric method recently developed by Erel and Neselioglu. RESULTS In patients with celiac disease, native thiol(P = 0.027) and total thiol(P = 0.031) levels were lower, while disulphide(P < 0.001) level, disulphide/native thiol(P < 0.001) and disulphide/total thiol(P < 0.001) ratios were higher compared to the control group. In patients who do not comply with a gluten-free diet, disulphide/native thiol ratio was found higher compared to the patients who comply with the diet(P < 0.001). In patients withany autoantibody-positive, disulphide/native thiol ratio was observed higher compared to the patients with autoantibody-negative(P < 0.05). It is found that there is a negative correlation between celiac autoantibodies, and native thiol, total thiol levels and native thiol/total thiol ratio, while a positive correlation is observed between disulphide, disulphide/native thiol and disulphide/total thiol levels.CONCLUSION This study is first in the literature which found that the patients with celiac disease the dynamic thiol/disulphide balance shifts through disulphide form compared to the control group.
