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.