Peripheral basophil activation: A hidden player in the immunopathogenesis of primary biliary cholangitis

BACKGROUND T helper 17 (Th17) cell infiltration and interleukin (IL)-17 secretion in intrahepatic small bile ducts is a critical driver of immune-mediated injury in primary biliary cholangitis (PBC). IL-6 is an essential upstream activator of Th17 cells. Basophil-derived IL-6 promotes the differentiation of CD4+ T cells and Th1 cells into Th17 cells, thereby regulating their immunological functions. AIM To investigate the activation status and cytokine expression of basophils in PBC, elucidating potential mechanisms through which basophils contribute to its pathogenesis. METHODS This single-center retrospective case-control study conducted at Guangdong Medical University Affiliated Hospital (China) between September 2019 and August 2024 enrolled 65 consecutive treatment-naïve patients with PBC (PBC group), 65 age- and sex-matched patients with chronic hepatitis B (CHB group), and 65 healthy controls (Normal group). Fourteen participants per group (subgroup) were randomly selected for flow cytometry analysis of basophil proportion, activation markers (CD203c and CD62 L mean fluorescence intensity), IL-6-positive basophils (IL-6+ basophils as a percentage of total basophils), and IL-17-positive T lymphocytes (CD3+CD4+IL-17+ cells) proportion among T cells. Data were analyzed using Kruskal-Wallis and χ 2 tests as appropriate. RESULTS Routine blood tests revealed significantly higher basophil counts and proportions in the PBC group compared to the CHB and Normal groups (P < 0.001 for both comparisons), with no significant differences between the CHB and Normal groups (P = 0.201). Flow cytometry revealed a higher basophil proportion in the PBC subgroup compared to the CHB (P = 0.011) and Normal subgroups (P < 0.001). The mean fluorescence intensity of CD203c on basophil surfaces was elevated in the PBC subgroup compared to the CHB (P = 0.032) and Normal subgroups (P = 0.039). The proportion of IL-6+ basophils was significantly higher in the PBC subgroup than in the CHB (P < 0.01) and Normal subgroups (P < 0.001). Similarly, the Th17 cell proportion was markedly elevated in the PBC compared to the CHB (P < 0.001) and Normal subgroups (P < 0.001). CONCLUSION Patients with PBC have increased peripheral basophil counts with enhanced activation. Activated basophils have increased IL-6 expression, which may indirectly induce Th17 cell proliferation and contribute to PBC pathogenesis.