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Anti‐kelch‐like 12 and anti‐hexokinase 1: novel autoantibodies in primary biliary cirrhosis
Author(s) -
Norman Gary L.,
Yang ChenYen,
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
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12690
Subject(s) - primary biliary cirrhosis , autoantibody , antibody , medicine , serology , immunology , autoimmune hepatitis , cirrhosis , gastroenterology , hepatitis
Background & Aims Using high‐density human recombinant protein microarrays, we identified two potential biomarkers, kelch‐like 12 ( KLHL 12) and hexokinase‐1 ( HK 1), in primary biliary cirrhosis ( PBC ). The objective of this study was to determine the diagnostic value of anti‐ KLHL 12/ HK 1 autoantibodies in PBC . Initial discovery used sera from 22 patients with PBC and 62 non‐ PBC controls. KLHL 12 and HK 1 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. Methods Serum 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 . Results Anti‐ KLHL 12 and anti‐ HK 1 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‐ HK 1 and anti‐ KLHL 12 with available markers ( MIT 3, gp210 and sp100), increased the diagnostic sensitivity for PBC . Most importantly, anti‐ KLHL 12 and anti‐ HK 1 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 . Conclusions The addition of tests for highly specific anti‐ KLHL 12 and anti‐ HK 1 antibodies to AMA and ANA serological assays significantly improves efficacy in the clinical detection and diagnosis of PBC , especially for AMA ‐negative subjects.