BACKGROUND Primary biliary cholangitis(PBC)is a serious disease that causes significant morbidity.PBC is confirmed with liver biopsy but autoantibodies are frequently used as proxies for diagnosis.The performance of a...BACKGROUND Primary biliary cholangitis(PBC)is a serious disease that causes significant morbidity.PBC is confirmed with liver biopsy but autoantibodies are frequently used as proxies for diagnosis.The performance of autoantibodies for the diagnosis of PBC seems to vary widely across populations.AIM To assess the diagnostic performance of several autoantibodies for the diagnosis of PBC in Latin American individuals.METHODS We studied 85 female adult Colombians,43 cases with biopsy-confirmed PBC and 42 controls in whom a liver biopsy ruled out PBC.Plasma anti-mitochondrial antibodies(AMAs),anti-smooth muscle antibodies(ASMAs)and anti-nuclear antibodies(ANAs),as well as total immunoglobulin(Ig)M and IgG were determined using immunofluorescence or enzyme-linked immunosorbent assay in all study participants within 1 year of the biopsy.For all variables,values analyzed were those closest to the date of the biopsy.Patients with viral or alcoholic hepatitis were excluded.RESULTS Mean age at diagnosis was 58.7 years for cases and 56.9 years for controls,and the body mass index was lower among cases.Most cases received ursodeoxycholic acid,while most controls received vitamin E.Sjögren syndrome and Hashimoto’s thyroiditis were the most frequent autoimmune comorbidities of PBC.The prevalence of AMA positivity among PBC cases was unexpectedly low.The sensitivity and specificity values were respectively 44.2%and 76.2%for AMA,74.4%and 38.1%for ANA,14.0%and 73.8%for ASMA,26.7%and 80.0%for IgG,and 57.1%and 85.7%for IgM.The combination of positive AMA plus positive IgM had 91%positive predictive value for PBC.Among AMA-negative cases,the most prevalent antibodies were ANA(87.5%).In all,62%of AMA-positive and 84.6%of IgM-positive individuals had fibrosis in their biopsy.CONCLUSION AMA positivity was very low among female Latin American patients with PBC.The performance of all antibodies was quite limited.These results highlight the urgent need for better PBC biomarkers.展开更多
Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease characterized by immune-driven destruction of small intrahepatic bile ducts leading a proportion of patients to hepatic failure over the years.Dia...Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease characterized by immune-driven destruction of small intrahepatic bile ducts leading a proportion of patients to hepatic failure over the years.Diagnosis at early stages in concert with ursodeoxycholic acid treatment has been linked with prevention of disease progression in the majority of cases.Diagnosis of PBC in a patient with cholestasis relies on the detection of disease-specific autoantibodies,including anti-mitochondrial antibodies,and disease-specific anti-nuclear antibodies targeting sp100 and gp210.These autoantibodies assist the diagnosis of the disease,and are amongst few autoantibodies the presence of which is included in the diagnostic criteria of the disease.They have also become important tools evaluating disease prognosis.Herein,we summarize existing data on detection of PBC-related autoantibodies and their clinical significance.Moreover,we provide insight on novel autoantibodies and their possible prognostic role in PBC patients.展开更多
Primary biliary cirrhosis(PBC) is a chronic,progressive,cholestatic,organ-specific autoimmune disease of unknown etiology.It predominantly affects middle-aged women,and is characterized by autoimmune-mediated destruct...Primary biliary cirrhosis(PBC) is a chronic,progressive,cholestatic,organ-specific autoimmune disease of unknown etiology.It predominantly affects middle-aged women,and is characterized by autoimmune-mediated destruction of small-and medium-size intrahepatic bile ducts,portal inflammation and progressive scarring,which without proper treatment can ultimately lead to fibrosis and hepatic failure.Serum autoantibodies are crucial tools for differential diagnosis of PBC.While it is currently accepted that antimitochondrial antibodies are the most important serological markers of PBC,during the last five decades more than sixty autoantibodies have been explored in these patients,some of which had previously been thought to be specific for other autoimmune diseases.展开更多
Autoimmune cholangitis would be the appropriate name to define the immune-mediated bile duct injury following the breakdown of tolerance to mitochondrial proteins and the appearance of serum autoantibodies and autorea...Autoimmune cholangitis would be the appropriate name to define the immune-mediated bile duct injury following the breakdown of tolerance to mitochondrial proteins and the appearance of serum autoantibodies and autoreactive T cells.Nevertheless,the conditionis universally named primary biliary cirrhosis(PBC).The disease etiology and pathogenesis remain largely unknown despite the proposed lines of evidence.One twin study and numerous epidemiology reportssuggest that both a susceptible genetic background and environmental factors determine disease onsetwhile a recent genome-wide association study proposed highly significant associations with several commongenetic polymorphisms in subgroups of patients.Specific infectious agents and chemicals may contribute to the disease onset and perpetuation in a geneticallysusceptible host,possibly through molecular mimicry.Importantly,several murine models have been proposed and include strains in which PBC is genetically determined or induced by immunization with chemicals and bacteria.From a pathogenetic standpoint,new exciting data have demonstrated the unique apoptotic features of bile duct cells that allow the mitochondrial autoantigens to be taken up in their intact form within apoptotic blebs.We are convinced that the application of the most recent molecular techniques will soon pro-vide developments in PBC etiology and pathogenesis with likely implications in diagnostics and therapeutics.展开更多
AIM To explore the pathogenesis of primary biliary cholangitis(PBC) by identifying candidate autoantibodies in serum samples by proteomics and bioinformatics.METHODS Nine antimitochondrial antibody(AMA)-positive PBC p...AIM To explore the pathogenesis of primary biliary cholangitis(PBC) by identifying candidate autoantibodies in serum samples by proteomics and bioinformatics.METHODS Nine antimitochondrial antibody(AMA)-positive PBC patients and nine age-and sex-matched AMA-negative PBC patients were recruited. Antigen enrichment technology was applied to capture autoantigens of human intrahepatic biliary epithelial cells(Hi BECs) that are recognized by autoantibodies from the sera of PBC patients. Candidate autoantigens were identified by label-free mass spectrometry. Bioinformatics analysis with Max Quant software(version 1.5.2.8),DAVID platform,and Cytoscape v.3.0 allowed illustration of pathways potentially involved in the pathogenesis of PBC.RESULTS In total,1081 candidate autoantigen proteins were identified from the PBC patient pool. Among them,371 were determined to be significantly differentially expressed between AMA-positive and-negative PBC patients(P < 0.05). Fisher's exact test was performed for enrichment analysis of Gene Ontology protein annotations(biological processes,cellular components,and molecular functions) and the Kyoto Encyclopedia of Genes and Genomes pathways. Significantly different protein categories were revealed between AMA-positive and-negative PBC patients. As expected,autoantigens related to mitochondria were highly enriched in AMApositive PBC patients. However,lower levels of AMA were also detected in AMA-negative PBC patients. In addition,autoantigens of AMA-negative PBC patients were mainly involved in B-cell activation,recognition of phagocytosis,and complement activation.CONCLUSION AMA-negative PBC individuals may not exist,but rather,those patients exhibit pathogenesis pathways different from those of AMA-positive PBC. Comprehensive research is needed to confirm these observations.展开更多
We are describing an interesting case of two chronic liver diseases in a 48-year-old Chinese woman.While chronic hepatitis B is a common entity in Asia,the patient was later found to have active,asymptomatic primary b...We are describing an interesting case of two chronic liver diseases in a 48-year-old Chinese woman.While chronic hepatitis B is a common entity in Asia,the patient was later found to have active,asymptomatic primary biliary cirrhosis due to a persistently elevated alkaline phosphatase level after optimal hepatitis B virus DNA suppression on antiviral therapy.This report emphasizes the importance of keeping a high index of suspicion for another potential liver disease process even after a patient has been successfully treated for a primary liver condition.Clinical vigilance,especially in atypical clinical presentations,can result in early accurate diagnosis and prompt treatment.展开更多
文摘BACKGROUND Primary biliary cholangitis(PBC)is a serious disease that causes significant morbidity.PBC is confirmed with liver biopsy but autoantibodies are frequently used as proxies for diagnosis.The performance of autoantibodies for the diagnosis of PBC seems to vary widely across populations.AIM To assess the diagnostic performance of several autoantibodies for the diagnosis of PBC in Latin American individuals.METHODS We studied 85 female adult Colombians,43 cases with biopsy-confirmed PBC and 42 controls in whom a liver biopsy ruled out PBC.Plasma anti-mitochondrial antibodies(AMAs),anti-smooth muscle antibodies(ASMAs)and anti-nuclear antibodies(ANAs),as well as total immunoglobulin(Ig)M and IgG were determined using immunofluorescence or enzyme-linked immunosorbent assay in all study participants within 1 year of the biopsy.For all variables,values analyzed were those closest to the date of the biopsy.Patients with viral or alcoholic hepatitis were excluded.RESULTS Mean age at diagnosis was 58.7 years for cases and 56.9 years for controls,and the body mass index was lower among cases.Most cases received ursodeoxycholic acid,while most controls received vitamin E.Sjögren syndrome and Hashimoto’s thyroiditis were the most frequent autoimmune comorbidities of PBC.The prevalence of AMA positivity among PBC cases was unexpectedly low.The sensitivity and specificity values were respectively 44.2%and 76.2%for AMA,74.4%and 38.1%for ANA,14.0%and 73.8%for ASMA,26.7%and 80.0%for IgG,and 57.1%and 85.7%for IgM.The combination of positive AMA plus positive IgM had 91%positive predictive value for PBC.Among AMA-negative cases,the most prevalent antibodies were ANA(87.5%).In all,62%of AMA-positive and 84.6%of IgM-positive individuals had fibrosis in their biopsy.CONCLUSION AMA positivity was very low among female Latin American patients with PBC.The performance of all antibodies was quite limited.These results highlight the urgent need for better PBC biomarkers.
文摘Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease characterized by immune-driven destruction of small intrahepatic bile ducts leading a proportion of patients to hepatic failure over the years.Diagnosis at early stages in concert with ursodeoxycholic acid treatment has been linked with prevention of disease progression in the majority of cases.Diagnosis of PBC in a patient with cholestasis relies on the detection of disease-specific autoantibodies,including anti-mitochondrial antibodies,and disease-specific anti-nuclear antibodies targeting sp100 and gp210.These autoantibodies assist the diagnosis of the disease,and are amongst few autoantibodies the presence of which is included in the diagnostic criteria of the disease.They have also become important tools evaluating disease prognosis.Herein,we summarize existing data on detection of PBC-related autoantibodies and their clinical significance.Moreover,we provide insight on novel autoantibodies and their possible prognostic role in PBC patients.
文摘Primary biliary cirrhosis(PBC) is a chronic,progressive,cholestatic,organ-specific autoimmune disease of unknown etiology.It predominantly affects middle-aged women,and is characterized by autoimmune-mediated destruction of small-and medium-size intrahepatic bile ducts,portal inflammation and progressive scarring,which without proper treatment can ultimately lead to fibrosis and hepatic failure.Serum autoantibodies are crucial tools for differential diagnosis of PBC.While it is currently accepted that antimitochondrial antibodies are the most important serological markers of PBC,during the last five decades more than sixty autoantibodies have been explored in these patients,some of which had previously been thought to be specific for other autoimmune diseases.
文摘Autoimmune cholangitis would be the appropriate name to define the immune-mediated bile duct injury following the breakdown of tolerance to mitochondrial proteins and the appearance of serum autoantibodies and autoreactive T cells.Nevertheless,the conditionis universally named primary biliary cirrhosis(PBC).The disease etiology and pathogenesis remain largely unknown despite the proposed lines of evidence.One twin study and numerous epidemiology reportssuggest that both a susceptible genetic background and environmental factors determine disease onsetwhile a recent genome-wide association study proposed highly significant associations with several commongenetic polymorphisms in subgroups of patients.Specific infectious agents and chemicals may contribute to the disease onset and perpetuation in a geneticallysusceptible host,possibly through molecular mimicry.Importantly,several murine models have been proposed and include strains in which PBC is genetically determined or induced by immunization with chemicals and bacteria.From a pathogenetic standpoint,new exciting data have demonstrated the unique apoptotic features of bile duct cells that allow the mitochondrial autoantigens to be taken up in their intact form within apoptotic blebs.We are convinced that the application of the most recent molecular techniques will soon pro-vide developments in PBC etiology and pathogenesis with likely implications in diagnostics and therapeutics.
基金Supported by the National Natural Science Foundation of China,No.81302591,No.81373188,and No.81671618the Capital Health Research and Development of Special,No.2014-1-4011the Research Special Fund for Public Welfare Industry of Health,No.201202004
文摘AIM To explore the pathogenesis of primary biliary cholangitis(PBC) by identifying candidate autoantibodies in serum samples by proteomics and bioinformatics.METHODS Nine antimitochondrial antibody(AMA)-positive PBC patients and nine age-and sex-matched AMA-negative PBC patients were recruited. Antigen enrichment technology was applied to capture autoantigens of human intrahepatic biliary epithelial cells(Hi BECs) that are recognized by autoantibodies from the sera of PBC patients. Candidate autoantigens were identified by label-free mass spectrometry. Bioinformatics analysis with Max Quant software(version 1.5.2.8),DAVID platform,and Cytoscape v.3.0 allowed illustration of pathways potentially involved in the pathogenesis of PBC.RESULTS In total,1081 candidate autoantigen proteins were identified from the PBC patient pool. Among them,371 were determined to be significantly differentially expressed between AMA-positive and-negative PBC patients(P < 0.05). Fisher's exact test was performed for enrichment analysis of Gene Ontology protein annotations(biological processes,cellular components,and molecular functions) and the Kyoto Encyclopedia of Genes and Genomes pathways. Significantly different protein categories were revealed between AMA-positive and-negative PBC patients. As expected,autoantigens related to mitochondria were highly enriched in AMApositive PBC patients. However,lower levels of AMA were also detected in AMA-negative PBC patients. In addition,autoantigens of AMA-negative PBC patients were mainly involved in B-cell activation,recognition of phagocytosis,and complement activation.CONCLUSION AMA-negative PBC individuals may not exist,but rather,those patients exhibit pathogenesis pathways different from those of AMA-positive PBC. Comprehensive research is needed to confirm these observations.
文摘We are describing an interesting case of two chronic liver diseases in a 48-year-old Chinese woman.While chronic hepatitis B is a common entity in Asia,the patient was later found to have active,asymptomatic primary biliary cirrhosis due to a persistently elevated alkaline phosphatase level after optimal hepatitis B virus DNA suppression on antiviral therapy.This report emphasizes the importance of keeping a high index of suspicion for another potential liver disease process even after a patient has been successfully treated for a primary liver condition.Clinical vigilance,especially in atypical clinical presentations,can result in early accurate diagnosis and prompt treatment.
