Detection of Autoantibodies Against Nucleoporin p62 in Sera of Patients With Primary Biliary Cholangitis

Abstract

Background Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by specific autoantibodies. We evaluated the prevalence of autoantibodies against nucleoporin p62 (anti-p62) in PBC patients' sera to determine whether it can be a marker for PBC, in comparison with other immunological and biochemical parameters. We validated the performance of our in-house ELISA technique. Methods Serum samples were collected from 135 PBC patients. Thirty patients with primary sclerosing cholangitis (PSC) and 30 with autoimmune hepatitis (AIH) were included as pathological controls, and 40 healthy blood donors served as healthy controls. The presence of anti-p62 was determined by an in-house ELISA using a recombinant protein. We calculated the sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratio (LR+ and LR−) of our in-house ELISA for diagnosing PBC based on anti-p62. Findings were correlated with biochemical data and survival. Results Anti-p62 was detected in 32 PBC patients (23.7%). Specificity and PPV of anti-p62 for PBC were 99% and 97%, respectively. The difference between proportions of anti-p62-positive patients and controls was 0.23 (95% confidence interval [CI]: 0.03–0.40; P <0.0001); LR+ and LR− were 23.7 and 0.77, respectively. The presence of anti-p62 was associated with higher levels of bilirubin and alkaline phosphatase ( P <0.001). The odds ratio for survival was 2.44 (95% CI: 0.87–6.87; P =0.091). Conclusions Anti-p62 may be regarded as a significant serological marker of PBC.

Analysis of Autoantibodies against Promyelocytic Leukemia Nuclear Body Components and Biochemical Parameters in Sera of Patients with Primary Biliary Cholangitis

“…The ANA pattern in PBC includes multiple nuclear dots (MND-ANA) and nuclear membrane-associated ANAs (NM-ANAs). About 30% of patients manifest anti-nuclear envelope (NE) positivity [ 13 , 14 , 15 , 16 ]. In the majority of cases, anti-NM antibodies target gp210 and p62 proteins.…”

Six autoantibodies as potential differential biomarkers of hepatocellular carcinoma vs. liver cirrhosis and chronic hepatitis: A prospective multi‑institutional study

“…Previous studies have reported that s-p62-Abs are positive not only for cancers such as HCC, colorectal cancer, and breast cancer but also for conditions characterized by chronic inflammation and fibrosis, such as primary biliary cholangitis ( 2 , 5 , 26 , 27 ). Even in our study, the positivity rate of s-p62-Abs was not significantly higher in patients with HCC than in those with LC and CH.…”

Changed Profile of Serum Transferrin Isoforms in Primary Biliary Cholangitis

“…Optical density (OD) was measured with an automatic plate reader (Multiscan RC, Labsystem, Vantaa, Finland). Detection of anti-p62 antibodies was performed according to the procedure described by Bauer and Habior [17].…”