Identification of New Autoantigens for Primary Biliary Cirrhosis Using Human Proteome Microarrays*

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown etiology and is considered to be an autoimmune disease. Autoantibodies are important tools for accurate diagnosis of PBC. Here, we employed serum profiling analysis using a human proteome microarray composed of about 17,000 full-length unique proteins and identified 23 proteins that correlated with PBC. To validate these results, we fabricated a PBC-focused microarray with 21 of these newly identified candidates and nine additional known PBC antigens. By screening the PBC microarrays with additional cohorts of 191 PBC patients and 321 controls (43 autoimmune hepatitis, 55 hepatitis B virus, 31 hepatitis C virus, 48 rheumatoid arthritis, 45 systematic lupus erythematosus, 49 systemic sclerosis, and 50 healthy), six proteins were confirmed as novel PBC autoantigens with high sensitivities and specificities, including hexokinase-1 (isoforms I and II), Kelch-like protein 7, Kelch-like protein 12, zinc finger and BTB domain-containing protein 2, and eukaryotic translation initiation factor 2C, subunit 1. To facilitate clinical diagnosis, we developed ELISA for Kelch-like protein 12 and zinc finger and BTB domain-containing protein 2 and tested large cohorts (297 PBC and 637 control sera) to confirm the sensitivities and specificities observed in the microarray-based assays. In conclusion, our research showed that a strategy using high content protein microarray combined with a smaller but more focused protein microarray can effectively identify and validate novel PBC-specific autoantigens and has the capacity to be translated to clinical diagnosis by means of an ELISA-based method.

• Publication year

  2012

• Venue

  Molecular & Cellular Proteomics

• Publication date

  2012-05-30

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/mcp.M111.015529PMID 22647870PMCID PMC3434773
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Rapid Identification of Monospecific Monoclonal Antibodies Using a Human Proteome Microarray*

  2012cited by this paper
• Disease-specific autoantibodies in primary biliary cirrhosis.

  2011cited by this paper
• Primary biliary cirrhosis.

  2011cited by this paper
• Identification of a novel autoantigen in inflammatory bowel disease by protein microarray

  2011cited by this paper
• Autoantibodies to GW bodies and other autoantigens in primary biliary cirrhosis

  2011cited by this paper
• Historical perspectives on the discovery and elucidation of autoantibodies to centromere proteins (CENP) and the emerging importance of antibodies to CENP-F.

  2011cited by this paper
• A Protein Allergen Microarray Detects Specific IgE to Pollen Surface, Cytoplasmic, and Commercial Allergen Extracts

  2010cited by this paper
• Differential detection of nuclear envelope autoantibodies in primary biliary cirrhosis using routine and alternative methods

  2010cited by this paper
• Novel autoimmune hepatitis-specific autoantigens identified using protein microarray technology.

  2010cited by this paper
• PML Nuclear Body Component Sp140 Is a Novel Autoantigen in Primary Biliary Cirrhosis

  2010cited by this paper
• Primary biliary cirrhosis: a 2010 update.

  2010cited by this paper
• Antibodies against the voltage-dependent anion channel (VDAC) and its protective ligand hexokinase-I in children with autism.

  2010cited by this paper
• Anti-CENP-B antibodies are associated with prolonged survival in breast cancer.

  2010cited by this paper
• Genome‐wide profiling of humoral immune response to Coxiella burnetii infection by protein microarray

  2010cited by this paper
• Primary biliary cirrhosis: what do autoantibodies tell us?

  2010cited by this paper
• Protein microarrays: high-throughput tools for proteomics

  2009cited by this paper
• Identification of Tumor-associated Autoantigens for the Diagnosis of Colorectal Cancer in Serum Using High Density Protein Microarrays*

  2009cited by this paper
• ZBTB2, a Novel Master Regulator of the p53 Pathway*

  2009cited by this paper
• Female predominance and X chromosome defects in autoimmune diseases.

  2009cited by this paper
• Anti-proteasome activator 28α is a novel anti-cytoplasmic antibody in patients with systemic lupus erythematosus and Sjögren’s syndrome

  2009influential reference
• Identification of Novel Serological Biomarkers for Inflammatory Bowel Disease Using Escherichia coli Proteome Chip*

  2009cited by this paper
• Primary biliary cirrhosis

  2009cited by this paper
• Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling.

  2009cited by this paper
• Detection of novel non-M2-related antimitochondrial antibodies in patients with anti-M2 negative primary biliary cirrhosis

  2009cited by this paper
• Primary Biliary Cirrhosis (PBC), PBC Autoantibodies, and Hepatic Parameter Abnormalities in a Large Population of Systemic Sclerosis Patients

  2009cited by this paper
• Pathogenesis of primary biliary cirrhosis.

  2008cited by this paper
• Natural history of primary biliary cirrhosis.

  2008cited by this paper
• New autoantigens in rheumatoid arthritis (RA): screening 8268 protein arrays with sera from patients with RA

  2008cited by this paper
• Long‐term follow‐up of antimitochondrial antibody–positive autoimmune hepatitis

  2008influential reference
• The unfinished business of primary biliary cirrhosis.

  2008cited by this paper
• Antimitochondrial antibodies and other antibodies in primary biliary cirrhosis: diagnostic and prognostic value.

  2008cited by this paper
• Antigen microarrays identify unique serum autoantibody signatures in clinical and pathologic subtypes of multiple sclerosis

  2008cited by this paper
• Frequency, Behavior, and Prognostic Implications of Antimitochondrial Antibodies in Type 1 Autoimmune Hepatitis

  2008influential reference
• Integral Protein Microarrays for the Identification of Lung Cancer Antigens in Sera That Induce a Humoral Immune Response*S

  2008cited by this paper
• Liver transplantation in primary biliary cirrhosis.

  2008cited by this paper
• New insights into autoimmune liver diseases

  2008cited by this paper
• The value of antinuclear antibodies in primary biliary cirrhosis

  2008cited by this paper
• ANTINUCLEAR ANTIBODIES: GENERAL INTRODUCTION

  2007cited by this paper
• Anti‐gp210 and anti‐centromere antibodies are different risk factors for the progression of primary biliary cirrhosis

  2007cited by this paper
• Measurement of gp210 autoantibodies in sera of patients with primary biliary cirrhosis

  2007cited by this paper
• AUTOIMMUNE, CHOLESTATIC AND BILIARY DISEASE Antimitochondrial Antibodies in Acute Liver Failure: Implications for Primary Biliary Cirrhosis

  2007cited by this paper
• Nuclear envelope protein autoantigens in primary biliary cirrhosis

  2007cited by this paper
• The presence of anti-mitochondrial antibodies in Chinese patients with liver involvement in systemic lupus erythematosus

  2006influential reference
• Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis

  2006cited by this paper
• Severe acute respiratory syndrome diagnostics using a coronavirus protein microarray.

  2006cited by this paper
• Circulating auto-antibodies against nuclear and non-nuclear antigens in primary Sjögren's syndrome

  2006cited by this paper
• The KLHL12–Cullin-3 ubiquitin ligase negatively regulates the Wnt–β-catenin pathway by targeting Dishevelled for degradation

  2006cited by this paper
• Risk factors and comorbidities in primary biliary cirrhosis: A controlled interview‐based study of 1032 patients

  2005cited by this paper
• Prevalence and clinical significance of isotype specific antinuclear antibodies in primary biliary cirrhosis

  2005cited by this paper
• Clinical features and prognosis of primary biliary cirrhosis associated with systemic sclerosis

  2005cited by this paper
• Prevalence of Anticentromere F Protein Autoantibodies in 347 Patients with Non‐Hodgkin's Lymphoma

  2005cited by this paper
• Antigen microarray profiling of autoantibodies in rheumatoid arthritis.

  2005cited by this paper
• A Retrospective Study on Clinical Features and Prognostic Factors of Biopsy-Proven Primary Biliary Cirrhosis in Chinese Patients

  2005cited by this paper
• Antinuclear Antibodies in Primary Biliary Cirrhosis

  2005cited by this paper
• Antimitochondrial antibodies in patients with chronic hepatitis C virus infection: description of 18 cases and review of the literature

  2005cited by this paper
• Identification of specific autoantigens in Sjögren's syndrome by SEREX

  2005cited by this paper
• Do antinuclear antibodies in primary biliary cirrhosis patients identify increased risk for liver failure?

  2004cited by this paper
• Antibodies in scleroderma: Direct pathogenicity and phenotypic associations

  2004influential reference
• Liver transplantation for primary biliary cirrhosis.

  2003cited by this paper
• Association of Primary Biliary Cirrhosis and Rheumatoid Arthritis

  2003cited by this paper
• Antinuclear antibodies specific for primary biliary cirrhosis.

  2003cited by this paper
• Pathogenesis of primary biliary cirrhosis.

  2003cited by this paper
• The epidemiology of primary biliary cirrhosis.

  2003cited by this paper
• Profile and clinical significance of anti-nuclear envelope antibodies found in patients with primary biliary cirrhosis: a multicenter study.

  2003cited by this paper
• Connective tissue diseases and the liver.

  2002cited by this paper
• Global Analysis of Protein Activities Using Proteome Chips

  2001cited by this paper
• Detection of antimitochondrial autoantibodies in immunofluorescent AMA‐negative patients with primary biliary cirrhosis using recombinant autoantigens

  2001cited by this paper
• Management of primary biliary cirrhosis

  2000cited by this paper
• Management of primary biliary cirrhosis. The American Association for the Study of Liver Diseases practice guidelines.

  2000cited by this paper
• Circulating anticentromere CENP-A and CENP-B antibodies in patients with diffuse and limited systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis.

  2000influential reference
• Clinical significance of anticentromere antibodies in patients with systemic lupus erythematosus.

  2000influential reference
• The kelch repeat superfamily of proteins: propellers of cell function.

  2000cited by this paper
• Variant forms of cholestatic diseases involving small bile ducts in adults

  2000cited by this paper
• Primary biliary cirrhosis

  1998cited by this paper
• The antinuclear autoantibodies Sp100 and gp210 persist after orthotopic liver transplantation in patients with primary biliary cirrhosis.

  1998cited by this paper
• Identification of the cDNA for human red blood cell-specific hexokinase isozyme.

  1997cited by this paper
• Comparison of the clinical features and clinical course of antimitochondrial antibody‐positive and ‐negative primary biliary cirrhosis

  1997cited by this paper
• Molecular bases of hexokinase deficiency.

  1997cited by this paper
• Antimitochondrial antibodies in primary biliary cirrhosis.

  1997cited by this paper
• Specificity and sensitivity of gp210 autoantibodies detected using an enzyme‐linked immunosorbent assay and a synthetic polypeptide in the diagnosis of primary biliary cirrhosis

  1996cited by this paper
• Autoantibodies against nucleoporin p62 constitute a novel marker of primary biliary cirrhosis.

  1996cited by this paper
• Identification and Characterization of a Leukocyte-specific Component of the Nuclear Body*

  1996cited by this paper
• Autoantibodies from patients with primary biliary cirrhosis recognize a region within the nucleoplasmic domain of inner nuclear membrane protein LBR

  1996cited by this paper
• High prevalence of antibodies to recombinant CENP‐B in primary biliary cirrhosis: Nuclear immunofluorescence patterns and ELISA reactivities

  1995cited by this paper
• The POZ domain: a conserved protein-protein interaction motif.

  1994cited by this paper
• Autoantibodies against integral membrane proteins of the nuclear envelope in patients with primary biliary cirrhosis.

  1994cited by this paper
• The BTB domain, found primarily in zinc finger proteins, defines an evolutionarily conserved family that includes several developmentally regulated genes in Drosophila.

  1994cited by this paper
• Sera from patients with tuberculosis recognize the M2a‐epitope (E2‐subunit of pyruvate dehydrogenase) specific for primary biliary cirrhosis

  1993cited by this paper
• Antimitochondrial antibodies in primary biliary cirrhosis and other disorders: definition and clinical relevance.

  1992cited by this paper
• IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis.

  1992cited by this paper
• Isolation and characterization of cDNA encoding a human nuclear antigen predominantly recognized by autoantibodies from patients with primary biliary cirrhosis.

  1990cited by this paper
• Identification and characterization of autoantibodies against the nuclear envelope lamin B receptor from patients with primary biliary cirrhosis

  1990cited by this paper
• Characterisation of the reactivity of autoantibodies in primary biliary cirrhosis

  1989cited by this paper
• The E1 alpha and beta subunits of the pyruvate dehydrogenase complex are M2'd' and M2'e' autoantigens in primary biliary cirrhosis.

  1989cited by this paper
• Detection of autoantibodies to recombinant mitochondrial proteins in patients with primary biliary cirrhosis.

  1989cited by this paper
• Primary biliary cirrhosis: identification of two major M2 mitochondrial autoantigens.

  1988cited by this paper
• Identification and specificity of a cDNA encoding the 70 kd mitochondrial antigen recognized in primary biliary cirrhosis.

  1987cited by this paper
• Primary Biliary Cirrhosis

  1987cited by this paper
• Mitochondrial antibodies in primary biliary cirrhosis: Species and nonspecies specific determinants of M2 antigen

  1985cited by this paper
• Antinuclear antibodies in primary biliary cirrhosis.

  1984cited by this paper

• Autoantibodies in Primary Biliary Cholangitis: From Classical Markers to Emerging Targets

  2025cites this paper
• Bacterial proteome microarray technology in biomedical research.

  2025cites this paper
• Serum autoantibodies against hexokinase 1 manifest secondary to diabetic macular edema onset.

  2024cites this paper
• An autoantibody profile identified by human genome‐wide protein arrays in rheumatoid arthritis

  2024cites this paper
• A Glimpse into Humoral Response and Related Therapeutic Approaches of Takayasu’s Arteritis

  2024cites this paper
• PhIP-Seq: methods, applications and challenges

  2024cites this paper
• Screening of Cancer-Specific Biomarkers for Hepatitis B-Related Hepatocellular Carcinoma Based on a Proteome Microarray

  2024cites this paper
• Identification and validation of anti-protein arginine methyltransferase 5 (PRMT5) antibody as a novel biomarker for systemic sclerosis (SSc)

  2024cites this paper
• Clinical Significance of Uncommon, Non-Clinical, and Novel Autoantibodies.

  2024cites this paper
• Linee guida SIPMeL per la determinazione degli autoanticorpi nella diagnosi delle malattie autoimmuni del fegato

  2024cites this paper
• A Novel IgG–IgM Autoantibody Panel Enhances Detection of Early-stage Lung Adenocarcinoma from Benign Nodules

  2024cites this paper
• Human antibody profiling technologies for autoimmune disease

  2023cites this paper
• Progress in the Application of Proteomics Technology in Traditional Chinese Medicine Research

  2023cites this paper
• Autoimmune Markers in Primary Biliary Cholangitis.

  2023cites this paper
• GDF-15 Inhibits ADP-Induced Human Platelet Aggregation through the GFRAL/RET Signaling Complex

  2023cites this paper
• Role of autoantibodies in the clinical management of primary biliary cholangitis

  2023cites this paper
• Autoantibody screening of plasma and peritoneal fluid of patients with endometriosis.

  2023cites this paper
• Current advances in antibody‐based serum biomarker studies: From protein microarray to phage display

  2022cites this paper
• Multiple rather than specific autoantibodies were identified in irritable bowel syndrome with HuProt™ proteome microarray

  2022cites this paper
• Anticorps anti-hexokinase-1 et anti-kelch-like 12, de nouveaux marqueurs de la cholangite biliaire primitive

  2022cites this paper
• Diagnostic and Clinical Value of Specific Autoantibodies against Kelch-like 12 Peptide and Nuclear Envelope Proteins in Patients with Primary Biliary Cholangitis

  2022cites this paper
• The Role of B Cells and B Cell Therapies in Immune-Mediated Liver Diseases

  2021cites this paper
• Identification and characterization of the antigen recognized by the germ cell mAb TRA98 using a human comprehensive wet protein array

  2021cites this paper
• Analytical and Biochemical Perspectives of Protein O-GlcNAcylation.

  2021cites this paper
• Novel autoantibodies identified in ACPA-negative rheumatoid arthritis

  2021cites this paper
• Three-dimensional protein microarrays fabricated on reactive microsphere modified COC substrates.

  2021cites this paper
• Changes of Serum IgG Glycosylation Patterns in Primary Biliary Cholangitis Patients

  2021influential citation
• Applications of Protein Microarrays in Biomarker Discovery for Autoimmune Diseases

  2021cites this paper
• Promyelocytic Leukemia Antigen Expression: a Histological Marker for Primary Biliary Cholangitis Diagnosis?

  2021cites this paper
• Identification of novel serological autoantibodies in Takayasu arteritis patients using HuProt arrays.

  2020cites this paper
• Identification of Novel Serological Autoantibodies in Takayasu Arteritis Patients Using HuProt Arrays

  2020cites this paper
• Detection of Anti-kelch-like 12 and Anti-hexokinase 1 Antibodies in Primary Biliary Cholangitis Patients in China.

  2020cites this paper
• Antigen presentation, autoantibody production, and therapeutic targets in autoimmune liver disease

  2020cites this paper
• Immunometabolic Pathways and Its Therapeutic Implication in Autoimmune Diseases

  2020cites this paper
• Developments and Applications of Functional Protein Microarrays*

  2020influential citation
• Evaluation of a novel extended automated particle-based multi-analyte assay for the detection of autoantibodies in the diagnosis of primary biliary cholangitis

  2020cites this paper
• Novel Anti-Hexokinase 1 Antibodies Are Associated With Poor Prognosis in Patients With Primary Biliary Cholangitis.

  2020cites this paper
• The Prevalence of Anti-Hexokinase-1 and Anti-Kelch-Like 12 Peptide Antibodies in Patients With Primary Biliary Cholangitis Is Similar in Europe and North America: A Large International, Multi-Center Study

  2019cites this paper
• Quantitative proteomic analyses in blood: A window to human health and disease

  2019cites this paper
• Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus

  2019cites this paper
• Serum Clusterin and Complement Factor H May Be Biomarkers Differentiate Primary Sjögren's Syndrome With and Without Neuromyelitis Optica Spectrum Disorder

  2019cites this paper
• Autoimmune diseases in China.

  2019cites this paper
• Protein Microarrays

  2019cites this paper
• Plasma proteomic and autoantibody profiles reveal the proteomic characteristics involved in longevity families in Bama, China

  2019cites this paper
• Pathophysiology of primary biliary cholangitis.

  2018cites this paper
• The role of proteomics in the age of immunotherapies

  2018cites this paper
• Biomarkers for primary biliary cholangitis: current perspectives

  2018cites this paper
• A toolbox of immunoprecipitation-grade monoclonal antibodies to human transcription factors

  2018cites this paper
• Proteome-wide Tyrosine Phosphorylation Analysis Reveals Dysregulated Signaling Pathways in Ovarian Tumors*

  2018cites this paper
• Immunological Enrichment of Low-Abundance Proteins for Comparative Proteomics

  2017cites this paper
• Global Analysis of SUMO-Binding Proteins Identifies SUMOylation as a Key Regulator of the INO80 Chromatin Remodeling Complex*

  2017cites this paper
• Protein Array-based Approaches for Biomarker Discovery in Cancer

  2017cites this paper
• Advances in the development of human protein microarrays

  2017cites this paper
• PTMA, a new identified autoantigen for oral submucous fibrosis, regulates oral submucous fibroblast proliferation and extracellular matrix

  2017cites this paper
• Phenotyping and auto-antibody production by liver-infiltrating B cells in primary sclerosing cholangitis and primary biliary cholangitis.

  2017cites this paper
• Identification of novel autoantigens via mass spectroscopy-based antibody-mediated identification of autoantigens (MS-AMIDA) using immune thrombocytopenic purpura (ITP) as a model disease.

  2017cites this paper
• AAgMarker 1.0: a resource of serological autoantigen biomarkers for clinical diagnosis and prognosis of various human diseases

  2017cites this paper
• Exploring pathogenesis of primary biliary cholangitis by proteomics: A pilot study

  2017cites this paper
• A toolbox of immunoprecipitation-grade monoclonal antibodies against human transcription factors

  2017cites this paper
• The Virus–Host Interactome

  2016cites this paper
• Systematic protein interactome analysis of glycosaminoglycans revealed YcbS as a novel bacterial virulence factor

  2016cites this paper
• Immunoproteomics technologies in the discovery of autoantigens in autoimmune diseases

  2016cites this paper
• Applications in high-content functional protein microarrays.

  2016cites this paper
• Recent advances in the diagnosis and treatment of primary biliary cholangitis

  2016cites this paper
• Molecular diagnostic testing for primary biliary cholangitis

  2016influential citation
• Omics: Data Processing and Analysis

  2016cites this paper
• Serum proteomic signatures as biomarkers of primary biliary cirrhosis diagnosis and prognosis.

  2016cites this paper
• A contemporary perspective on the molecular characteristics of mitochondrial autoantigens and diagnosis in primary biliary cholangitis

  2016cites this paper
• The NIH Protein Capture Reagents Program (PCRP): a standardized protein affinity reagent toolbox

  2016cites this paper
• Identification of Novel Biomarkers for Behcet Disease Diagnosis Using Human Proteome Microarray Approach*

  2016cites this paper
• Advancing translational research with next‐generation protein microarrays

  2016cites this paper
• Making Sense of Autoantibodies in Cholestatic Liver Diseases.

  2016cites this paper
• Primary biliary cholangitis in China

  2016cites this paper
• Identification of disease-specific motifs in the antibody specificity repertoire via next-generation sequencing

  2016cites this paper
• Systematic Analysis of Intracellular-targeting Antimicrobial Peptides, Bactenecin 7, Hybrid of Pleurocidin and Dermaseptin, Proline–Arginine-rich Peptide, and Lactoferricin B, by Using Escherichia coli Proteome Microarrays*

  2016cites this paper
• An overview of innovations and industrial solutions in Protein Microarray Technology

  2016cites this paper
• Clinical Potential of Regulatory T Cell Therapy in Liver Diseases: An Overview and Current Perspectives

  2016influential citation
• Exploration of high-density protein microarrays for antibody validation and autoimmunity profiling.

  2016cites this paper
• Rnaset2 inhibits melanocyte outgrowth possibly through interacting with shootin1.

  2015cites this paper
• Anti‐kelch‐like 12 and anti‐hexokinase 1: novel autoantibodies in primary biliary cirrhosis

  2015cites this paper
• Two of Them Do It Better: Novel Serum Biomarkers Improve Autoimmune Hepatitis Diagnosis

  2015cites this paper
• Discovering cancer biomarkers from clinical samples by protein microarrays

  2015cites this paper
• Autoantibody Profiling on Human Proteome Microarray for Biomarker Discovery in Cerebrospinal Fluid and Sera of Neuropsychiatric Lupus

  2015cites this paper
• Serological comparative proteomics analysis of mitochondrial autoantibody‐negative and ‐positive primary biliary cirrhosis

  2015cites this paper
• Identification of SUMO E3 ligase-specific substrates using the HuProt human proteome microarray.

  2015cites this paper
• Identification of proteins that interact with alpha A-crystallin using a human proteome microarray

  2014cites this paper
• Protein microarrays for studies of drug mechanisms and biomarker discovery in the era of systems biology.

  2014cites this paper
• 3D-Epoxyoberflächen für DNA-codierte Proteinarrays

  2014cites this paper
• Autoantibodies in Primary Biliary Cirrhosis

  2014cites this paper
• The Diagnosis and Classification of Immune-Mediated Hepatic Diseases

  2014cites this paper
• Biomarker Discovery for Heterogeneous Diseases

  2013cites this paper
• New Centromere Autoantigens Identified in Systemic Sclerosis Using Centromere Protein Microarrays

  2013cites this paper
• Identification of autoantigens in body fluids by combining pull-downs and organic precipitations of intact immune complexes with quantitative label-free mass spectrometry.

  2013cites this paper
• Autoantibodies and Biomarker Discovery

  2013cites this paper
• Functional protein microarray as molecular decathlete: A versatile player in clinical proteomics

  2012cites this paper