Evolving liver inflammation in biochemically normal individuals with anti-mitochondria antibodies.

Abstract

Background: Anti-mitochondria autoantibodies (AMA) occur in > 95% primary biliary cholangitis (PBC) patients. Biochemically normal AMA-positive (BN/AMA+) individuals, occasionally noticed by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed in AMA-specific assays, may represent early stages of PBC. The Enhanced Liver Fibrosis (ELF) score is a surrogate marker for liver fibrosis. This prospective study investigated the ELF score in BN/AMA+ individuals and PBC patients, considering autoantibody avidity and serum levels along the years.

Methods: 327 samples from 35 PBC and 59 BN/AMA+ were prospectively obtained in average 3.83 (range 0.50-7.40) years apart. Samples were tested by IIF on rat-kidney (IIF-AMA), western-blot for AMA (WB-AMA), and ELISA for antibodies against pyruvate-dehydrogenase (PDC-E2), gp210, sp100 and CENP-A/B. Anti-PDC-E2 avidity was determined by 6 M urea-elution ELISA. Alkaline phosphatase (ALP), gamma glutamyl transferase (ɣGT) and ELF score were measured by automated methods.

Results: Along the follow-up period BN/AMA+ subjects and PBC patients presented significant increase in serum anti-PDC-E2 (mean 10.45% and 8.86% per year; respectively), anti-PDC-E2 avidity (3.02% and 4.94%/year) and ELF score (3.24% and 2.71%/year). IIF-AMA and ɣGT increased in BN/AMA+ (6.59% and 2.36%) and decreased in PBC (- 4.89%/year and - 3.88%/year). In BN/AMA+ individuals there was positive correlation of ELF with IIF-AMA titer (r = 0.465; p < 0.001) and with anti-PDC-E2 levels (r = 0.239; p < 0.001). Expansion of autoantibody targets along time occurred in 39% BN/AMA+ and 49% PBC patients. The frequency of BN/AMA+ with high probability of having established PBC increased from 7 to 14%.

Conclusions: BN/AMA+ individuals present an orchestrated increase in ELF score and humoral autoimmune response over time, indicating an opportunity for early therapeutic intervention and prevention in autoimmunity.