A preliminary study on the role of the E2 subunit of pyruvate dehydrogenase modified by xenobiotics in the pathogenesis of primary biliary cholangitis

Abstract

Objective To explore preliminarily the role of the E2 subunit of pyruvate dehydrogenase (PDC-E2) modified by xenobiotics (e.g. 2-octynic acid, 2-OA) in the pathogenesis of primary biliary cirrhosis (PBC). Methods Patients of PBC (102 cases), primary sclerosing cholangitis (PSC, 34 cases) and healthy controls (HC, 50 cases) were selected. The anti-PDC-E2, anti-2-OA and anti-lipoic acid (LA) antibody in the peripheral blood of the 3 groups were tested by enzyme linked immunosorbent assay (ELISA). By inhibitive ELISA (iELISA), 30 of the 102 PBC patients with anti-PDC-E2 antibody but without anti-2-OA antibody were selected to detect whether there was any new epitope on the PEC-E2 conjugated with 2-OA. The chi-square test and Fisher exact test were taken to analyze the enumeration data. The two-tailed unpaired t test with Welch's correction was used to compare the measurement data. Spearman rank correlation analysis was also employed for proper test. Results The positive rate of anti-PDC-E2, anti-LA and anti-2-OA antibody in PBC patients was 94.1% (96/102), 73.5% (73/102) and 53.9%(55/102) respectively, all of which were statistically significantly higher than those in healthy controls group but were of no significant difference between PSC and healthy controls group. There was no significant relevance between the levels of Anti-LA and anti-2-OA antibody in the PBC group (r=-0.065, P=0.520). The iELISA results showed that the antibody, which only identified the epitopes on 2-OA-PDC-E2 induced by the 2-OA conjugation with PDC-E2, existed in 40% (12/30) of the PBC patients, and more interestingly, this antibody was predominantly appeared in PBC patients at their early clinical stage. Conclusion There are anti-LA antibody and anti-2-OA antibody in PBC patients, which have shown no significant association with each other. It is very likely that new antigenic conformational epitopes on PDC-E2 modified by 2-OA would emerge, which might led to the immune response in the individuals who are susceptible to PBC, and thus contribute for the breaking of PDC-E2 immune tolerance, and PBC occurrence finally. Key words: Liver cirrhosis, biliary; E2 subunit of Pyruvate dehydrogenase; Pathogenesis