Profiling of circulating T follicular helper and T peripheral helper cell subsets in patients with primary biliary cholangitis

Primary biliary cholangitis (PBC) is a common chronic cholestatic autoimmune liver disease that may progress to liver fibrosis or cirrhosis if not accurately diagnosed and promptly treated. T follicular helper (Tfh) cells and T peripheral helper (Tph) cells, as subsets of T cells that assist B cells in producing antibodies, are closely related to the pathogenesis of autoimmune diseases. This research aims to explore the potential of Tfh and Tph cells as biomarkers for PBC disease progression. We recruited 30 PBC patients, 25 post-hepatitis B cirrhosis (PHBC) patients, and 30 healthy subjects. Both Tfh and Tph cells were significantly enriched in the peripheral blood of PBC patients, and their frequencies were correlated with autoantibody production. Area under the ROC curve (AUC) analysis demonstrated that Tfh and Tph cell frequencies exhibited convergent diagnostic performance with anti-mitochondrial antibody (AMA) in discriminating PBC patients from healthy controls. Furthermore, the frequencies of these cells were positively correlated with liver enzyme levels (ALT, AST, and GGT), suggesting that they may indicate liver and bile duct damage in PBC patients. The frequency of Tfh cells was negatively correlated with total protein (TP) and albumin (ALB) levels, indicating that the increase of Tfh cells was related to the impairment of hepatocyte function. Additionally, the frequencies of Tfh and Tph cells were positively correlated with IgM levels, showing that these cells seem to be involved in the production of immunoglobulins. Together, Tfh and Tph cells can serve as biomarkers for both diagnosing PBC and correlating with disease severity.