Celiac disease (CD) is a common autoimmune condition.Previously it was considered to be a rare childhood disorder,but is actually considered a relatively common condition,present at any age,which may have multiple com...Celiac disease (CD) is a common autoimmune condition.Previously it was considered to be a rare childhood disorder,but is actually considered a relatively common condition,present at any age,which may have multiple complications and manifestations.Hematological disorders of the disease are not uncommon.Among these disorders,the most frequently reported are anemias as a result of iron deficiency,often associated with folate and/or B12 deficiency.Anemias caused by hemolysis are very rarely reported in celiac patients.An 11-year-old girl with a previous uneventful medical history presented with severe hemolytic anemia.Hemolysis was Coombs negative,accompanied by inappropriate low reticulocyte count,despite exaggerated bone marrow hyperplasia of the erythroid precursors which showed normal maturation.Serology for recent infections,including EpsteinBarr virus,parvovirus B19,cytomegalovirus and mycoplasma,were all negative.Levels of serum IgA,IgG and IgM,were all within normal ranges for age.Screeningfor anti-DNA,antinuclear,antineutrophil cytoplasmic,antimicrosomal,antithyroglobulin,and antimitochondrial antibodies and lupus anticoagulants,was negative.She was also negative for human immunodeficiency virus.Conventional therapy with corticosteroids and intravenous immunoglobulin failed.CD was serendipitously discovered upon screening for anti-tissue transglutaminase autoantibodies.The disease was confirmed by biopsy of the small intestine mucosa.The patient recovered with gluten-free diet.A unique case of CD is presented.CD should be serologically screened in each patient with Coombs negative "immune"hemolytic anemia,particularly if accompanied by "reticulocytopenia".A new hemolytic mechanism and very speculative explanation for "reticulocytopenia"are discussed.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 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 establish the diagnostic performance of sev-eral serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potentia...AIM: To establish the diagnostic performance of sev-eral serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potential se- rological algorithms to reduce the necessity for biopsy. METHODS: We prospectively performed duodenal biopsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. Blood samples were tested using six assays (enzyme-linked immunosorbent assay) that detected antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay combinations, it would be possible to reach or rule out diagnosis of CD without biopsy in 92% of cases in both pretest populations. We observed that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. CONCLUSION: The DGP/tTG Screen assay could be considered as the best initial test for CD. Combinations of two tests, including a DGP/tTG Screen, might be able to diagnose CD accurately in different clinical scenarios making biopsy avoidable in a high proportion of subjects.展开更多
Celiac disease （CD） is a common autoimmune disorder, induced by the intake of gluten proteins present in wheat, barley and rye. Contrary to common belief, this disorder is a protean systemic disease, rather than mer...Celiac disease （CD） is a common autoimmune disorder, induced by the intake of gluten proteins present in wheat, barley and rye. Contrary to common belief, this disorder is a protean systemic disease, rather than merely a pure digestive alteration. CD is closely associated with genes that code HLA-Ⅱ antigens, mainly of DQ2 and DQ8 classes. Previously, it was considered to be a rare childhood disorder, but is actually considered a frequent condition, present at any age, which may have multiple complications. Tissue transglutaminase-2 （tTG）, appears to be an important component of this disease, both, in its pathogenesis and diagnosis. Active CD is characterized by intestinal and/or extra-intestinal symptoms, villous atrophy and crypt hyperplasia, and strongly positive tTG auto-antibodies. The duodenal biopsy is considered to be the ＂gold standard＂ for diagnosis, but its practice has significant limitations in its interpretation, especially in adults. Occasionally, it results in a false-negative because of patchy mucosal changes and the presence of mucosal villous atrophy is often more severe in the proximal jejunum, usually not reached by endoscopic biopsies. CD is associated with increased rates of several diseases, such as iron deficiency anemia, osteoporosis, dermatitis herpetiformis, several neurologic and endocrine diseases, persistent chronic hypertransami-nasemia of unknown origin, various types of cancer and other autoimmune disorders. Treatment of CD dictates a strict, life-long gluten-free diet, which results in remission for most individuals, although its effect on some associated extraintestinal manifestations remains to be established.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
Celiac disease is an immune-mediated disorder that causes severe architectural disturbance in the small intestinal mucosa of genetically-predisposed individuals.Impaired absorption of multiple nutrients results and di...Celiac disease is an immune-mediated disorder that causes severe architectural disturbance in the small intestinal mucosa of genetically-predisposed individuals.Impaired absorption of multiple nutrients results and diarrhea and weight loss develop.Evidence has accumulated that a strict gluten-free diet can result in resolution of diarrhea,weight gain and normalization of nutrient malabsorption.In addition,histopathological changes also normalize,but this histopathological res-ponse appears to be time-dependent,sex-dependent and age-dependent.Compliance to a gluten-free diet is difficult and costly resulting in poor compliance and only a limited clinical response.This poses a risk for later long-term complications,including malignancy.A major practical clinical problem is the assessment of compliance to the gluten-free diet.Although symptoms may resolve and serological antibody markers may improve,multiple studies have documented ongoing architectural disturbance and inflammatory change,and with these continued inflammatory changes,a persistent risk for long-term complications.Recent immunological studies have suggested that peptides can be detected in both urine and fecal specimens that may be indicative of limited compliance.At the same time,multiple biopsy studies have demonstrated that complete normalization of the mucosa may occur in some patients within 6 mo of initiation of a gluten-free diet,but more often,up to 2 years or more may be required before repeated biopsies eventually show mucosal recovery and mucosal healing.展开更多
文摘Celiac disease (CD) is a common autoimmune condition.Previously it was considered to be a rare childhood disorder,but is actually considered a relatively common condition,present at any age,which may have multiple complications and manifestations.Hematological disorders of the disease are not uncommon.Among these disorders,the most frequently reported are anemias as a result of iron deficiency,often associated with folate and/or B12 deficiency.Anemias caused by hemolysis are very rarely reported in celiac patients.An 11-year-old girl with a previous uneventful medical history presented with severe hemolytic anemia.Hemolysis was Coombs negative,accompanied by inappropriate low reticulocyte count,despite exaggerated bone marrow hyperplasia of the erythroid precursors which showed normal maturation.Serology for recent infections,including EpsteinBarr virus,parvovirus B19,cytomegalovirus and mycoplasma,were all negative.Levels of serum IgA,IgG and IgM,were all within normal ranges for age.Screeningfor anti-DNA,antinuclear,antineutrophil cytoplasmic,antimicrosomal,antithyroglobulin,and antimitochondrial antibodies and lupus anticoagulants,was negative.She was also negative for human immunodeficiency virus.Conventional therapy with corticosteroids and intravenous immunoglobulin failed.CD was serendipitously discovered upon screening for anti-tissue transglutaminase autoantibodies.The disease was confirmed by biopsy of the small intestine mucosa.The patient recovered with gluten-free diet.A unique case of CD is presented.CD should be serologically screened in each patient with Coombs negative "immune"hemolytic anemia,particularly if accompanied by "reticulocytopenia".A new hemolytic mechanism and very speculative explanation for "reticulocytopenia"are discussed.
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.
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 (in part) A Grant from the Consejo de Investig-ación en Salud del Ministerio de Salud del Gobierno Autónomo de la Ciudad de Buenos Aires, Argentina
文摘AIM: To establish the diagnostic performance of sev-eral serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potential se- rological algorithms to reduce the necessity for biopsy. METHODS: We prospectively performed duodenal biopsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. Blood samples were tested using six assays (enzyme-linked immunosorbent assay) that detected antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay combinations, it would be possible to reach or rule out diagnosis of CD without biopsy in 92% of cases in both pretest populations. We observed that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. CONCLUSION: The DGP/tTG Screen assay could be considered as the best initial test for CD. Combinations of two tests, including a DGP/tTG Screen, might be able to diagnose CD accurately in different clinical scenarios making biopsy avoidable in a high proportion of subjects.
文摘Celiac disease （CD） is a common autoimmune disorder, induced by the intake of gluten proteins present in wheat, barley and rye. Contrary to common belief, this disorder is a protean systemic disease, rather than merely a pure digestive alteration. CD is closely associated with genes that code HLA-Ⅱ antigens, mainly of DQ2 and DQ8 classes. Previously, it was considered to be a rare childhood disorder, but is actually considered a frequent condition, present at any age, which may have multiple complications. Tissue transglutaminase-2 （tTG）, appears to be an important component of this disease, both, in its pathogenesis and diagnosis. Active CD is characterized by intestinal and/or extra-intestinal symptoms, villous atrophy and crypt hyperplasia, and strongly positive tTG auto-antibodies. The duodenal biopsy is considered to be the ＂gold standard＂ for diagnosis, but its practice has significant limitations in its interpretation, especially in adults. Occasionally, it results in a false-negative because of patchy mucosal changes and the presence of mucosal villous atrophy is often more severe in the proximal jejunum, usually not reached by endoscopic biopsies. CD is associated with increased rates of several diseases, such as iron deficiency anemia, osteoporosis, dermatitis herpetiformis, several neurologic and endocrine diseases, persistent chronic hypertransami-nasemia of unknown origin, various types of cancer and other autoimmune disorders. Treatment of CD dictates a strict, life-long gluten-free diet, which results in remission for most individuals, although its effect on some associated extraintestinal manifestations remains to be established.
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.
文摘Celiac disease is an immune-mediated disorder that causes severe architectural disturbance in the small intestinal mucosa of genetically-predisposed individuals.Impaired absorption of multiple nutrients results and diarrhea and weight loss develop.Evidence has accumulated that a strict gluten-free diet can result in resolution of diarrhea,weight gain and normalization of nutrient malabsorption.In addition,histopathological changes also normalize,but this histopathological res-ponse appears to be time-dependent,sex-dependent and age-dependent.Compliance to a gluten-free diet is difficult and costly resulting in poor compliance and only a limited clinical response.This poses a risk for later long-term complications,including malignancy.A major practical clinical problem is the assessment of compliance to the gluten-free diet.Although symptoms may resolve and serological antibody markers may improve,multiple studies have documented ongoing architectural disturbance and inflammatory change,and with these continued inflammatory changes,a persistent risk for long-term complications.Recent immunological studies have suggested that peptides can be detected in both urine and fecal specimens that may be indicative of limited compliance.At the same time,multiple biopsy studies have demonstrated that complete normalization of the mucosa may occur in some patients within 6 mo of initiation of a gluten-free diet,but more often,up to 2 years or more may be required before repeated biopsies eventually show mucosal recovery and mucosal healing.
