Diagnostic value of anti-hexokinase 1 and anti-kelch-like 12 antibodies in primary biliary cholangitis patients

Abstract

Objectives Anti-mitochondrial antibody (AMA) is not always present in patients with primary biliary cholangitis (PBC). We aimed to determine the additional value of anti-hexokinase 1 (anti-HK1) and anti-kelch-like 12 (anti-KLHL12) antibody in PBC and analyzed the biochemical and immunological parameters of 212 subjects, including PBC patients and healthy controls. Methods Serum anti-gp210 and sp100 antibodies were determined by an immunoblotting test (IBT). Enzyme-linked immunosorbent assay (ELISA) was employed to evaluate anti-HK1 and anti-KLHL12. The diagnostic value of anti-HK1 and anti-KLHL12 to PBC was analyzed by constructing a receiver operating characteristic (ROC) curve. Results ROC analyses didn’t show a very good performance of serum anti-HK1 for PBC diagnosis; the AUC was 0.664 with a sensitivity of 53.3 % and a specificity of 79.2 %. Regarding anti-KLHL12, ROC analysis yielded an AUC of 0.626, with a sensitivity of 45.7 % and a specificity of 93.8 %. For AMA-negative PBC patients, the AUC increased to 0.790 for KLHL12, and 0.708 for HK1. AMA combined with anti-HK1 or anti-KLHL12 antibody significantly improved the diagnostic sensitivity of PBC from 82 to about 95 %, respectively. In AMA-negative PBC patients, the sensitivities for anti-HK1 (62.50 %) and anti-KLHL12 (75 %) antibodies were higher than for anti-gp210 (37.5 %) and anti-sp100 antibody (43.75 %). When these four antibodies were combined, the overall sensitivity increased to 87.5 %. Conclusions The determination of anti-HK1 and anti-KLHL12 facilitates the diagnosis of PBC, particularly in AMA-negative patients. Adding anti-HK1 and anti-KLHL12 antibodies to clinical detection enables early diagnosis and timely treatment, potentially improving patient prognosis.