• Antinuclear antibodies
• Autoimmune non-rheumatic diseases
• Infectious diseases
• Methods of detection

• Humans
• Antibodies, Antinuclear/blood
• Antibodies, Antinuclear/immunology
• Autoimmune Diseases/immunology
• Autoimmune Diseases/diagnosis
• Autoimmune Diseases/blood
• Connective Tissue Diseases/diagnosis
• Connective Tissue Diseases/immunology
• Connective Tissue Diseases/blood
• Biomarkers/blood
• Enzyme-Linked Immunosorbent Assay
• Fluorescent Antibody Technique, Indirect/methods
• Prognosis

• AMA
• ANA
• Anti-mitochondrial antibody
• Antinuclear antibody
• Primary biliary cholangitis
• Sp100
• gp210

• Humans
• Autoantibodies
• Liver Cirrhosis, Biliary/diagnosis
• Antibodies, Antinuclear
• Cholestasis
• Biomarkers
• Cholangitis/diagnosis

Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by the gradual destruction of small intrahepatic bile ducts that eventually leads to liver cirrhosis, failure, and even carcinoma. The treatment options for PBC are limited, and the main treatment choices are the US Food and Drug Administration–approved ursodeoxycholic acid and obeticholic acid. However, many patients fail to respond adequately to these drugs and the adverse effects frequently lead to low life quality. For patients with end-stage PBC, liver transplantation remains the only effective treatment. Given their low immunogenicity, prominent immunomodulation property, differentiation potential, and tissue maintenance capacity, mesenchymal stem cells (MSCs) are emerging as new options for treating liver diseases, including PBC. Accumulating evidence from basic research to clinical studies supports the positive effects of MSC-based therapy for treating PBC. In this review, we characterized the underlying roles and mechanisms of MSCs for treating liver diseases and highlight recent basic and clinical advances in MSC-based therapy for treating PBC. Finally, the current challenges and perspectives for MSC-based therapy in clinical application are discussed, which could help accelerate the application of MSCs in clinical practice, especially for refractory diseases such as PBC.

Promyelocytic leukemia nuclear bodies (PML NBs) are multi-protein assemblies representing distinct sub-nuclear structures. As phase-separated molecular condensates, PML NBs exhibit liquid droplet-like consistency. A key organizer of the assembly and dynamics of PML NBs is the ubiquitin-like SUMO modification system. SUMO is covalently attached to PML and other core components of PML NBs thereby exhibiting a glue-like function by providing multivalent interactions with proteins containing SUMO interacting motifs (SIMs). PML NBs serve as the catalytic center for nuclear SUMOylation and SUMO-SIM interactions are essential for protein assembly within these structures. Importantly, however, formation of SUMO chains on PML and other PML NB-associated proteins triggers ubiquitylation and proteasomal degradation which coincide with disruption of these nuclear condensates. To date, a plethora of nuclear activities such as transcriptional and post-transcriptional regulation of gene expression, apoptosis, senescence, cell cycle control, DNA damage response, and DNA replication have been associated with PML NBs. Not surprisingly, therefore, SUMO-dependent PML NB integrity has been implicated in regulating many physiological processes including tumor suppression, metabolism, drug-resistance, development, cellular stemness, and anti-pathogen immune response. The interplay between PML NBs and viral infection is multifaceted. As a part of the cellular antiviral defense strategy, PML NB components are crucial restriction factors for many viruses and a mutual positive correlation has been found to exist between PML NBs and the interferon response. Viruses, in turn, have developed counterstrategies for disarming PML NB associated immune defense measures. On the other end of the spectrum, certain viruses are known to usurp specific PML NB components for successful replication and disruption of these sub-nuclear foci has recently been linked to the stimulation rather than curtailment of antiviral gene repertoire. Importantly, the ability of invading virions to manipulate the host SUMO modification machinery is essential for this interplay between PML NB integrity and viruses. Moreover, compelling evidence is emerging in favor of bacterial pathogens to negotiate with the SUMO system thereby modulating PML NB-directed intrinsic and innate immunity. In the current context, we will present an updated account of the dynamic intricacies between cellular PML NBs as the nuclear SUMO modification hotspots and immune regulatory mechanisms in response to viral and bacterial pathogens.

• bacteria
• intrinsic and innate immune response
• promyelocytic leukemia nuclear bodies
• small ubiquitin-related modifier
• viruses

• bromodomain
• cancer
• chromatin reader
• epigenetic gene regulation
• histone post-translational modifications
• protein-protein interaction network

• P01 CA240685 NCI NIH HHS
• R01 GM129338 NIGMS NIH HHS
• R01GM129338 NIGMS NIH HHS
• P01CA240685 NCI NIH HHS

Distinguishing primary biliary cholangitis (PBC) from other cholestatic diseases at the histological level could be assisted by new methods, such as immunohistochemical staining of specific antigens.

We evaluated whether the detection of promyelocytic leukemia protein (PML) can serve as a specific and sensitive marker for PBC diagnosis. Liver biopsies from 26 PBC patients, 20 primary sclerosing cholangitis (PSC), 37 viral hepatitis, 11 non-alcoholic steatohepatitis (NASH) and 5 normal patients were investigated after immunostaining with the anti-PML monoclonal PG-M3, IgG1 antibody.

Immunoreactivity in bile ducts was expressed by the PML-score (quotient of positive ducts to the total number of portal tracts multiplied by 2). PML-score was higher in PBC as compared to controls (P < 0.001). Using a cutoff of 0.18, PML-score proved highly sensitive (84.6%) and specific (89.7%) for confirming PBC as compared to only 5% of PSC, 9.1% of NASH and 13.5% of viral hepatitis patients (P < 0.001). Irrespective of the underlying disease, patients with PML-score > 0.18 were older (P = 0.007), more often females (P < 0.001) with higher ALP (P < 0.001), γ-GT (P = 0.001) and IgM (P < 0.001) compared to the patients with PML-score < 0.18.

We postulate that a simple PML immunohistochemical test could be sufficient for histopathological discrimination of PBC in problematic cases of undefined cholestatic disorders, including small-duct PSC and AMA-negative PBC cases.

• anti-PML antibodies
• anti-nuclear antibodies
• immunohistochemical staining
• primary biliary cholangitis
• primary sclerosing cholangitis

• ISG
• PML-NB
• Sp100
• epigenetics
• herpesviruses
• immunity

• Antigens, Nuclear
• Autoantigens
• Herpesviridae Infections
• Humans
• Nuclear Proteins
• Promyelocytic Leukemia Protein

• MC_UU_12014/5 Medical Research Council

Reference materials are important in the standardization of autoantibody testing and only a few are freely available for many known autoantibodies. Our goal was to develop three reference materials for antibodies to PML bodies/multiple nuclear dots (MND), antibodies to GW bodies (GWB), and antibodies to the nuclear mitotic apparatus (NuMA).

Reference materials for identifying autoantibodies to MND (MND-REF), GWB (GWB-REF), and NuMA (NuMA-REF) were obtained from three donors and validated independently by seven laboratories. The sera were characterized using indirect immunofluorescence assay (IFA) on HEp-2 cell substrates including two-color immunofluorescence using antigen-specific markers, western blot (WB), immunoprecipitation (IP), line immunoassay (LIA), addressable laser bead immunoassay (ALBIA), enzyme-linked immunosorbent assay (ELISA), and immunoprecipitation–mass spectrometry (IP-MS).

MND-REF stained 6–20 discrete nuclear dots that colocalized with PML bodies. Antibodies to Sp100 and PML were detected by LIA and antibodies to Sp100 were also detected by ELISA. GWB-REF stained discrete cytoplasmic dots in interphase cells, which were confirmed to be GWB using two-color immunofluorescence. Anti-Ge-1 antibodies were identified in GWB-REF by ALBIA, IP, and IP-MS. All reference materials produced patterns at dilutions of 1:160 or greater. NuMA-REF produced fine speckled nuclear staining in interphase cells and staining of spindle fibers and spindle poles. The presence of antibodies to NuMA was verified by IP, WB, ALBIA, and IP-MS.

MND-REF, GWB-REF, and NuMA-REF are suitable reference materials for the corresponding antinuclear antibodies staining patterns and will be accessible to qualified laboratories.

• GW body
• NuMA
• autoimmunity
• multiple nuclear dots
• reference materials

• HPV—human papillomavirus
• Innate immnuity
• L2 protein
• PML
• PML nuclear bodies
• infectious entry
• transcription

• ANA
• Antinuclear antibodies
• Autoantibodies
• HEp-2 cells
• Indirect immunofluorescence
• Standardization

• Antigens, Nuclear/metabolism
• Autoantigens/metabolism
• Capsid Proteins
• Cell Nucleus
• Genome, Viral
• Humans
• Intranuclear Inclusion Bodies
• Intranuclear Space
• Nuclear Proteins
• Papillomaviridae/genetics
• Papillomaviridae/metabolism
• Papillomaviridae/pathogenicity
• Promyelocytic Leukemia Protein/metabolism
• Promyelocytic Leukemia Protein/physiology
• SUMO-1 Protein/metabolism
• Transcription Factors
• Tumor Suppressor Proteins
• Virus Replication

• P30 GM110703 NIGMS NIH HHS
• R01 AI081809 NIAID NIH HHS
• R01 CA211576 NCI NIH HHS
• National Institute of Allergy and Infectious Diseases
• National Cancer Institute
• National Institute of General Medical Sciences

• AE2
• Biliary bicarbonate
• Cholangiocytes
• PBC
• miR-506

To investigate the prevalence and clinical significance of autoimmune liver disease (ALD)-related autoantibodies in patients with biliary atresia (BA).

Sera of 124 BA patients and 140 age-matched non-BA controls were assayed for detection of the following autoantibodies: ALD profile and specific anti-nuclear antibodies (ANAs), by line-blot assay; ANA and anti-neutrophil cytoplasmic antibody (ANCA), by indirect immunofluorescence assay; specific ANCAs and anti-M2-3E, by enzyme linked immunosorbent assay. Associations of these autoantibodies with the clinical features of BA (i.e., cytomegalovirus infection, degree of liver fibrosis, and short-term prognosis of Kasai procedure) were evaluated by Spearman’s correlation coefficient.

The overall positive rate of serum autoantibodies in preoperative BA patients was 56.5%. ALD profile assay showed that the positive reaction to primary biliary cholangitis-related autoantibodies in BA patients was higher than that to autoimmune hepatitis-related autoantibodies. Among these autoantibodies, anti-BPO was detected more frequently in the BA patients than in the controls (14.8% vs 2.2%, P < 0.05). Accordingly, 32 (25.8%) of the 124 BA patients also showed a high positive reaction for anti-M2-3E. By comparison, the controls had a remarkably lower frequency of anti-M2-3E (P < 0.05), with 6/92 (8.6%) of patients with other liver diseases and 2/48 (4.2%) of healthy controls. The prevalence of ANA in BA patients was 11.3%, which was higher than that in disease controls (3.3%, P < 0.05), but the reactivity to specific ANAs was only 8.2%. The prevalence of ANCAs (ANCA or specific ANCAs) in BA patients was also remarkably higher than that in the healthy controls (37.9% vs 6.3%, P < 0.05), but showed no difference from that in patients with other cholestasis. ANCA positivity was closely associated with the occurrence of postoperative cholangitis (r = 0.61, P < 0.05), whereas none of the autoantibodies showed a correlation to cytomegalovirus infection or the stages of liver fibrosis.

High prevalence of autoantibodies in the BA developmental process strongly reveals the autoimmune-mediated pathogenesis. Serological ANCA positivity may be a useful predictive biomarker of postoperative cholangitis.

• Biliary atresia
• Anti-nuclear antibody
• Anti-neutrophilic cytoplasmic antibody
• Autoimmune liver diseases
• Autoantibodies

• Antibodies, Antineutrophil Cytoplasmic/blood
• Antibodies, Antineutrophil Cytoplasmic/immunology
• Antibodies, Antinuclear/blood
• Autoantigens/immunology
• Biliary Atresia/blood
• Biliary Atresia/immunology
• Biliary Atresia/surgery
• Biomarkers/blood
• Cholangitis, Sclerosing/blood
• Cholangitis, Sclerosing/immunology
• Cytomegalovirus/isolation & purification
• Cytomegalovirus Infections/blood
• Cytomegalovirus Infections/immunology
• Cytomegalovirus Infections/virology
• Enzyme-Linked Immunosorbent Assay
• Female
• Fluorescent Antibody Technique, Indirect
• Hepatitis, Autoimmune/blood
• Hepatitis, Autoimmune/immunology
• Humans
• Infant
• Liver Cirrhosis/blood
• Liver Cirrhosis/immunology
• Male
• Portoenterostomy, Hepatic/adverse effects
• Portoenterostomy, Hepatic/methods
• Postoperative Complications/blood
• Postoperative Complications/epidemiology
• Postoperative Complications/etiology
• Preoperative Period
• Prognosis
• Retrospective Studies

Autoimmune liver diseases are conditions of low prevalence that comprise the triad of autoimmune hepatitis, primary biliary cholangitis (cirrhosis) and primary sclerosing cholangitis and their poorly characterised overlapping syndromes. Diagnostic autoantibodies are associated with autoimmune hepatitis and primary biliary cholangitis but not with primary sclerosing cholangitis. Autoantibodies are useful disease markers that facilitate early diagnosis of autoimmune hepatitis and primary biliary cholangitis and allow for therapeutic intervention to prevent progression to liver cirrhosis and associated complications. Adult onset type 1 autoimmune hepatitis is associated with F-actin reactive smooth muscle autoantibody, antinuclear autoantibody in 60% of patients, and autoantibody to SLA/LP in 15–20%. Juvenile onset type 2 autoimmune hepatitis is associated with LKM-1 and LC-1 autoantibodies. Primary biliary cholangitis is associated with a mitochondria-associated autoantibody designated M2 in >90% of patients and with disease-specific antinuclear autoantibodies in 50% that bind to antigens in the nuclear core complex and in multiple nuclear dots. Autoantibodies to the nuclear core complex target gp210, nucleoporin p62 and nuclear lamin B receptor. Autoantibodies to multiple nuclear dots target Sp100 and PML antigens. Liver autoantibodies in asymptomatic patients with normal liver function may precede the subsequent development of overt autoimmune liver disease. For routine diagnostic immunology laboratories, initial screening for liver autoantibodies by immunofluorescence remains the method of choice with confirmation for reactivity with their target antigen by enzyme-linked immunosorbent assay (ELISA) or line blot when required.

Aspects of intrinsic antiviral immunity are mediated by promyelocytic leukemia nuclear body (PML-NB) constituent proteins. During herpesvirus infection, these antiviral proteins are independently recruited to nuclear domains that contain infecting viral genomes to cooperatively promote viral genome silencing. Central to the execution of this particular antiviral response is the small ubiquitin-like modifier (SUMO) signaling pathway. However, the participating SUMOylation enzymes are not fully characterized. We identify the SUMO ligase protein inhibitor of activated STAT1 (PIAS1) as a constituent PML-NB protein. We show that PIAS1 localizes at PML-NBs in a SUMO interaction motif (SIM)-dependent manner that requires SUMOylated or SUMOylation-competent PML. Following infection with herpes simplex virus 1 (HSV-1), PIAS1 is recruited to nuclear sites associated with viral genome entry in a SIM-dependent manner, consistent with the SIM-dependent recruitment mechanisms of other well-characterized PML-NB proteins. In contrast to that of Daxx and Sp100, however, the recruitment of PIAS1 is enhanced by PML. PIAS1 promotes the stable accumulation of SUMO1 at nuclear sites associated with HSV-1 genome entry, whereas the accumulation of other evaluated PML-NB proteins occurs independently of PIAS1. We show that PIAS1 cooperatively contributes to HSV-1 restriction through mechanisms that are additive to those of PML and cooperative with those of PIAS4. The antiviral mechanisms of PIAS1 are counteracted by ICP0, the HSV-1 SUMO-targeted ubiquitin ligase, which disrupts the recruitment of PIAS1 to nuclear domains that contain infecting HSV-1 genomes through mechanisms that do not directly result in PIAS1 degradation.

IMPORTANCE Adaptive, innate, and intrinsic immunity cooperatively and efficiently restrict the propagation of viral pathogens. Intrinsic immunity mediated by constitutively expressed cellular proteins represents the first line of intracellular defense against infection. PML-NB constituent proteins mediate aspects of intrinsic immunity to restrict herpes simplex virus 1 (HSV-1) as well as other viruses. These proteins repress viral replication through mechanisms that rely on SUMO signaling. However, the participating SUMOylation enzymes are not known. We identify the SUMO ligase PIAS1 as a constituent PML-NB antiviral protein. This finding distinguishes a SUMO ligase that may mediate signaling events important in PML-NB-mediated intrinsic immunity. Moreover, this research complements the recent identification of PIAS4 as an intrinsic antiviral factor, supporting a role for PIAS proteins as both positive and negative regulators of host immunity to virus infection.

• antinuclear antibodies
• autoantibody
• autoimmunity
• consensus
• standardization

• antinuclear antibodies
• autoantibody
• autoimmunity
• consensus
• standardization

The SP100 family members comprise a set of closely related genes on chromosome 2q37.1. The widely expressed SP100 and the leukocyte-specific proteins SP110 and SP140 have been associated with transcriptional regulation and various human diseases. Here, we have characterized the SP100 family member SP140L. The genome sequence analysis showed the formation of SP140L gene through rearrangements of the two neighboring genes, SP100 and SP140, during the evolution of higher primates. The SP140L expression is interferon-inducible with high transcript levels in B cells and other peripheral blood mononuclear cells. Subcellularly, SP140L colocalizes with SP100 and SP140 in nuclear structures that are devoid of SP110, PML, or p300 proteins. Similarly to SP100 and SP140 protein, we detected serum autoantibodies to SP140L in patients with primary biliary cirrhosis using luciferase immunoprecipitation system and immunoblotting assays. In conclusion, our results show that SP140L is phylogenetically recent member of SP100 proteins and acts as an autoantigen in primary biliary cirrhosis patients.

• Antibodies, Antinuclear/analysis
• Antibodies, Antinuclear/immunology
• Antigens, Nuclear/immunology
• Autoantigens/immunology
• Humans
• Liver Cirrhosis, Biliary/diagnosis
• Liver Cirrhosis, Biliary/immunology
• Nuclear Pore Complex Proteins/immunology

• Adenovirus Infections, Human/immunology
• Adenoviruses, Human/genetics
• Adenoviruses, Human/metabolism
• Antigens, Nuclear/metabolism
• Autoantigens/metabolism
• Cell Line
• DNA Primers/genetics
• Fluorescent Antibody Technique, Indirect
• Gene Expression Regulation, Viral/genetics
• Humans
• Immunity, Innate/immunology
• Immunoblotting
• In Situ Hybridization
• Luciferases
• Nuclear Proteins/metabolism
• Promyelocytic Leukemia Protein
• Protein Isoforms/metabolism
• Real-Time Polymerase Chain Reaction
• Sumoylation
• Transcription Factors/metabolism
• Tumor Suppressor Proteins/metabolism

• 097945 Wellcome Trust

AIM: To investigate the presence of autoantibodies directed against liver sinusoidal cells in primary biliary cirrhosis (PBC).

METHODS: Liver biopsies from 21 PBC patients were studied and compared with 12 liver biopsies from disease controls [3 patients with hepatitis B (HBV) virus, 3 patients with hepatitis C virus (HCV), 3 patients with non-alcoholic steatohepatitis and 3 patients with acute alcoholic hepatitis (AAH)]. As healthy controls, we used tissue specimens adjacent to metastatic liver adenocarcinoma. Normal serum was taken from staff members of the unit. The determination of the cell type targeted by autoantibodies present in the patients sera was performed by indirect immunofluorescence (IIF) analysis using paraffin-embedded liver sections as a substrate. Sera from homologous or heterologous PBC patients or sera from the disease control group were used as primary antibodies. The presence of autoantibodies was identified using confocal microscopy.

RESULTS: In total, 18/21 (85.7%) PBC patients exhibited positive staining in the sinusoidal cells, 10/21 (47.6%) in lymphocytes, 8/21 (38%) in cholangiocytes and 7/21 (33.3%) in hepatocytes, when homologous serum and fluorescein isothiocyanate-conjugated immunoglobulin type G (IgG) secondary antibody were used. PBC sections incubated with heterologous PBC serum showed reduced staining (20% for sinusoidal cells, 20% for lymphocytes, 20% for cholangiocytes and 13.3% for hepatocytes). When IgM immunoglobulin, instead of IgG, was used as secondary antibody, positive staining was observed in 75% of lymphocytes, 62.5% of cholangiocytes, 37.5% of hepatocytes and 50% of the sinusoidal cells with a much stronger staining intensity. No staining was observed when either normal or PBC sera were used as a primary antibody on liver sections from the disease control group. When PBC sera were incubated with healthy control sections, weak positive staining of cholangiocytes was observed in 3/21 (14.3%) PBC serum samples. Steatohepatitis serum on PBC sections gave a positive staining of some hepatocytes and lymphocytes but no staining on viral hepatitis sections. Incubation with HBV sera stained some hepatocytes, cholangiocytes and intra-sinusoidal or portal lymphocytes of PBC, HBV and AAH patients but not HCV patients.

CONCLUSION: In this study, for the first time in diseased liver tissue, we have demonstrated that a large proportion of PBC patients have disease specific autoantibodies against liver sinusoidal cells.

• Primary biliary cirrhosis
• Autoantibodies
• Sinusoidal cells
• Cholangiocytes
• Liver tissue

It has been well established that numerous kinds of autoantibodies have been detected in liver disease. Some kinds of autoantibodies may be helpful in the diagnosis of autoimmune liver diseases including autoimmune hepatitis, primary biliary cirrhosis or primary sclerosing cholangitis. However, these autoantibodies are present even in sera of patients with viral hepatitis, drug-induced hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease and hepatocelluar carcinoma as well as in sera of patients with autoimmune liver diseases. Other kinds of autoantibodies are recognized as predictive hallmarks for disease activity or prognosis in liver diseases. On the other hand, treatment with interferon initiates the production of several types of autoantibodies in patients with chronic hepatitis C virus infection. Some of autoantibodies induced by interferon may postulate the treatment outcome in those patients. Recent studies also revealed the close correlation between oxidative stress and the production of autoantibodies in liver diseases. This article primarily reviews the recent advances of autoantibodies in the liver diseases and discusses the clinical significance of these autoantibodies.

• Autoantibodies
• Autoimmune liver diseases
• Diagnosis
• Disease activity
• Prognosis

• Adult
• Amino Acid Sequence
• Antibody Specificity
• Antigens, Nuclear/analysis
• Antigens, Nuclear/blood
• Antigens, Nuclear/genetics
• Antigens, Nuclear/immunology
• Autoantibodies/analysis
• Autoantibodies/blood
• Autoantibodies/immunology
• Autoantigens/analysis
• Autoantigens/blood
• Autoantigens/genetics
• Autoantigens/immunology
• Case-Control Studies
• Escherichia coli/genetics
• Follow-Up Studies
• Humans
• Immunoassay/methods
• Leukemia, Promyelocytic, Acute/diagnosis
• Leukemia, Promyelocytic, Acute/immunology
• Liver Cirrhosis, Biliary/diagnosis
• Liver Cirrhosis, Biliary/immunology
• Middle Aged
• Molecular Sequence Data
• Time Factors

• Antibodies, Antinuclear/immunology
• Antigens, Nuclear/immunology
• Autoantigens/immunology
• Biomarkers/metabolism
• Blotting, Western/methods
• Enzyme-Linked Immunosorbent Assay/methods
• Epitope Mapping
• Fluorescent Antibody Technique, Indirect/methods
• Humans
• Liver Cirrhosis, Biliary/diagnosis
• Liver Cirrhosis, Biliary/immunology
• Membrane Glycoproteins/immunology
• Nuclear Pore Complex Proteins/immunology
• Nuclear Proteins/immunology
• Prognosis
• Promyelocytic Leukemia Protein
• Receptors, Cytoplasmic and Nuclear/immunology
• Transcription Factors/immunology
• Tumor Suppressor Proteins/immunology
• Lamin B Receptor

• Antigens, Nuclear/metabolism
• Autoantigens/metabolism
• Cells, Cultured
• Cytomegalovirus/growth & development
• Cytomegalovirus/pathogenicity
• Gene Expression
• Gene Silencing
• Host-Pathogen Interactions
• Humans
• Immediate-Early Proteins/metabolism
• Virus Replication

• Animals
• Autoantibodies/immunology
• Humans
• Liver Cirrhosis, Biliary/diagnosis
• Liver Cirrhosis, Biliary/immunology
• Prevalence

• autoantibodies
• gw bodies
• primary biliary cirrhosis
• rna interference

• Adult
• Aged
• Antigens, Nuclear/immunology
• Autoantibodies/immunology
• Autoantigens/immunology
• Cytoplasmic Structures/immunology
• Female
• Humans
• Ketoglutarate Dehydrogenase Complex/immunology
• Liver Cirrhosis, Biliary/immunology
• Male
• Middle Aged
• Nuclear Pore Complex Proteins/immunology
• Nuclear Proteins/immunology
• Promyelocytic Leukemia Protein
• Proteins/immunology
• Pyruvate Dehydrogenase Complex/immunology
• RNA-Binding Proteins/immunology
• Retrospective Studies
• Ribonucleoproteins/immunology
• Transcription Factors/immunology
• Tumor Suppressor Proteins/immunology
• Young Adult

• Canadian Institutes of Health Research

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.

• Primary biliary cirrhosis
• Autoimmune disease
• Autoantibody
• Anti-mitochondrial antibody
• Anti-gp210 antibody
• Anti-sp100 antibody
• Anti-centromere antibodies

• Autoantibodies/blood
• Biomarkers
• Hepatitis, Autoimmune/blood
• Hepatitis, Autoimmune/diagnosis
• Humans
• Immunoenzyme Techniques

• Animals
• Antigens, Nuclear/metabolism
• Autoantigens/metabolism
• Cell Line
• Genome, Viral
• Herpesvirus 1, Bovine/chemistry
• Herpesvirus 1, Human/genetics
• Herpesvirus 1, Suid/chemistry
• Herpesvirus 3, Human/chemistry
• Humans
• Immediate-Early Proteins/physiology
• Nuclear Proteins/chemistry
• Nuclear Proteins/metabolism
• Promyelocytic Leukemia Protein
• Proteasome Endopeptidase Complex/physiology
• Response Elements
• Transcription Factors/metabolism
• Tumor Suppressor Proteins/metabolism
• Ubiquitin-Protein Ligases/metabolism
• Ubiquitin-Protein Ligases/physiology
• Viral Proteins/physiology

• MC_U130169966 Medical Research Council
• MC_UP_A550_1030 Medical Research Council
• MC_UU_12014/5 Medical Research Council

• Autoantibodies/immunology
• Biomarkers
• Cell Nucleus/immunology
• Humans
• Liver Cirrhosis, Biliary/diagnosis
• Liver Cirrhosis, Biliary/immunology
• Mitochondria/immunology
• Prognosis

• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/immunology
• Carcinoma, Hepatocellular/metabolism
• Cell Line, Tumor
• China
• Gene Expression Regulation, Neoplastic
• Histocompatibility Antigens Class I/immunology
• Histocompatibility Antigens Class I/isolation & purification
• Histocompatibility Antigens Class I/metabolism
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/immunology
• Liver Neoplasms/metabolism
• Neoplasm Proteins/metabolism
• Nuclear Proteins/metabolism
• Promyelocytic Leukemia Protein
• Proto-Oncogene Mas
• Proto-Oncogenes
• Transcription Factors/metabolism
• Tumor Suppressor Proteins/metabolism
• Up-Regulation

• TW 005900-01A2 FIC NIH HHS

• Cell Nucleus/pathology
• Cell Nucleus/ultrastructure
• Cell Nucleus/virology
• Fibroblasts/pathology
• Fibroblasts/virology
• Genome, Viral
• Herpes Simplex
• Herpesvirus 1, Human/genetics
• Humans
• In Situ Hybridization, Fluorescence
• Leukemia, Promyelocytic, Acute/pathology
• Nuclear Proteins/metabolism

• MC_U130169964 Medical Research Council
• MC_U130169966 Medical Research Council

• Antibodies/immunology
• Antigens, Nuclear/blood
• Antigens, Nuclear/immunology
• Autoantigens/blood
• Autoantigens/immunology
• Cell Line, Tumor
• Enzyme-Linked Immunosorbent Assay/methods
• Humans
• Mitochondria/immunology
• Nuclear Proteins/blood
• Nuclear Proteins/immunology