title: The Significance of Autoantibody Changes Over Time in Primary Biliary Cirrhosis.
abstract: OBJECTIVE
  In primary biliary cirrhosis (PBC), the antimitochondrial antibody is a cornerstone of diagnosis, but there have been conflicting reports about the correlation of autoantibodies with disease stage and prognosis. We studied whether autoantibody levels changed over time and sought correlations with clinical outcomes in a cohort of patients with PBC.
  
  
  METHODS
  We tested serial serum samples from patients with PBC at a research institution for several autoantibodies. Long-term clinical follow-up data were used to calculate the slopes (change over time) for autoantibodies, platelet count, Ishak fibrosis score, biopsy copper, and number of portal areas with bile ducts. An adverse clinical outcome was defined as hepatic decompensation, development of hepatocellular carcinoma, liver transplantation, or liver-related death. We performed linear or logistic regression or Fisher exact test as appropriate, adjusting for multiple comparisons.
  
  
  RESULTS
  Twenty-seven patients with PBC with 145 serum samples were studied. Of the cohort, 85% was white, 81% was female, and median follow-up time was 20 years. Of the autoantibodies tested, only sp100 changed significantly over time. The sp100 slope was inversely associated with the Ishak fibrosis slope (parameter estimate, -0.05; P = .0003).
  
  
  CONCLUSIONS
  While changes in most autoantibodies over time do not seem to correlate with clinical outcomes in PBC, a change in the sp100 autoantibody level may have prognostic utility with respect to the development of fibrosis on liver biopsy.
authors.affiliation: From the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; michele.tana@ucsf.edu.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Tana
authors.affiliation: Inova Diagnostics, San Diego, CA; and.
authors.forename: Zakera
authors.initials: Z
authors.lastname: Shums
authors.affiliation: Inova Diagnostics, San Diego, CA; and.
authors.forename: Jay
authors.initials: J
authors.lastname: Milo
authors.affiliation: Inova Diagnostics, San Diego, CA; and.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Norman
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Leung
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA.
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.affiliation: From the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD;
authors.forename: Mazen
authors.initials: M
authors.lastname: Noureddin
authors.affiliation: From the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD;
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.affiliation: From the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD;
authors.forename: Xiongce
authors.initials: X
authors.lastname: Zhao
authors.affiliation: From the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD;
authors.forename: Theo
authors.initials: T
authors.lastname: Heller
authors.affiliation: From the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD;
authors.forename: Jay H
authors.initials: JH
authors.lastname: Hoofnagle
mesh_terms: D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D034961:Antigens, Nuclear; D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; C066642:SP100 protein, human
keywords: Autoantibodies; Autoimmune liver disease; Primary biliary cirrhosis; Prognosis; Serum markers; Ursodiol