Comprehensive analysis of immune signatures in primary biliary cholangitis and autoimmune hepatitis

Abstract Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are autoimmune diseases that target hepatocytes and bile duct cells, respectively. Despite their shared autoimmune nature, the differences in immunologic characteristics between them remain largely unexplored. This study seeks to elucidate the unique immunological profiles of PBC and AIH and to identify key differences. We comprehensively analyzed various T cell subsets and their receptor expression in a cohort of 45 patients, including 27 PBC and 18 AIH cases. Both diseases exhibited T cell exhaustion and senescence along with a surge in inflammatory cytokines. Significantly increased CD38+HLA-DR+CD8+ T cell populations were observed in both diseases. AIH was characterized by an upregulation of CD8+ terminally differentiated T, CD4+ effector memory T, and CD4+ terminally differentiated T cells, and a concurrent reduction in regulatory T cells. In contrast, PBC displayed a pronounced presence of T follicular helper (Tfh) cells and a contraction of CD4−CD8− T cell populations. Correlation analysis revealed that NKP46+ natural killer frequency was closely tied to alanine aminotransferase and aspartate aminotransferase levels, and TIGIT expression on T cells was associated with globulin level in AIH. In PBC, there is a significant correlation between Tfh cells and ALP levels. Moreover, the identified immune landscapes in both diseases strongly related to disease severity. Through logistic regression analysis, γδ T, TIGIT+Vδ2 T, and Tfh1 cell frequencies emerged as distinct markers capable of differentiating PBC from AIH. In conclusion, our analyses reveal that PBC and AIH share similarities and differences regarding to immune profiles. γδ T, TIGIT+Vδ2 T, and Tfh1 cell frequencies are potential noninvasive immunological markers that can differentiate PBC from AIH.