Anti-kelch-like 12 and anti-hexokinase 1: novel autoantibodies in primary biliary cirrhosis

作者：Norman Gary L; Yang Chen Yen; Ostendorff Heather P; Shums Zakera; Lim Mark J; Wang Jinjun; Awad Amany; Hirschfield Gideon M; Milkiewicz Piotr; Bloch Donald B; Rothschild Kenneth J; Bowlus Christopher L; Adamopoulos Iannis E; Leung Patrick S C; Janssen Harry J; Cheung Angela C; Coltescu Catalina; Gershwin M Eric^*

来源：Liver International, 2015, 35(2): 642-651.

DOI：10.1111/liv.12690

• diagnostics
• liver
• serology

Background & AimsUsing high-density human recombinant protein microarrays, we identified two potential biomarkers, kelch-like 12 (KLHL12) and hexokinase-1 (HK1), in primary biliary cirrhosis (PBC). The objective of this study was to determine the diagnostic value of anti-KLHL12/HK1 autoantibodies in PBC. Initial discovery used sera from 22 patients with PBC and 62 non-PBC controls. KLHL12 and HK1 proteins were then analysed for immunoglobulin reactivity by immunoblot and enzyme-linked immunosorbent assay (ELISA) in two independent cohorts of PBC and disease/healthy control patients.
MethodsSerum samples from 100 patients with PBC and 165 non-PBC disease controls were analysed by immunoblot and samples from 366 patients with PBC, 174 disease controls, and 80 healthy donors were tested by ELISA.
ResultsAnti-KLHL12 and anti-HK1 antibodies were each detected more frequently in PBC compared with non-PBC disease controls (P<0.001). Not only are both markers highly specific for PBC (95%) but they also yielded higher sensitivity than anti-gp210 and anti-sp100 antibodies. Combining anti-HK1 and anti-KLHL12 with available markers (MIT3, gp210 and sp100), increased the diagnostic sensitivity for PBC. Most importantly, anti-KLHL12 and anti-HK1 antibodies were present in 10-35% of anti-mitochondrial antibody (AMA)-negative PBC patients and adding these two biomarkers to conventional PBC assays dramatically improved the serological sensitivity in AMA-negative PBC from 55% to 75% in immunoblot and 48.3% to 68.5% in ELISA.
ConclusionsThe addition of tests for highly specific anti-KLHL12 and anti-HK1 antibodies to AMA and ANA serological assays significantly improves efficacy in the clinical detection and diagnosis of PBC, especially for AMA-negative subjects.

• 出版日期2015-2