The Significance of Autoantibody Changes Over Time in Primary Biliary Cirrhosis

Abstract

Objectives 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.

The interplay of type I and type II interferons in murine autoimmune cholangitis as a basis for sex‐biased autoimmunity

“…± SEM, as described, with known positive and negative controls and standardized recombinant PDC‐E2 . Antibodies to SP100 were evaluated by ELISA using INOVA kits (INOVA Diagnostics, San Diego, CA) and again including known controls …”

The fingerprint of antimitochondrial antibodies and the etiology of primary biliary cholangitis

“…AMA can be detected before the appearance of disease symptoms. Although AMA is not associated with disease severity/prognosis, its presence before the development of liver pathology raises the possibility that it may contain information about early events in PBC. AMA recognize a unique conformational epitope within the inner lipoyl domain (ILD) of PDC‐E2 (amino acid [aa] residue 177‐314), and we have hypothesized that the loss of tolerance to PDC‐E2 is a result of chemical modification of this epitope following xenobiotic exposure .…”

Old and new treatments for primary biliary cholangitis

“…The hallmark serology of PBC is the anti‐mitochondrial antibody. While, no data have supported the hypothesis that reduction in AMA titres affects disease severity, immune modulation with B‐cell depleting agents has been considered given the production of immunoglobulins by B cells . Rituximab, a monoclonal antibody directed against the epitope of CD20 on the surface of B cells has been studied.…”