B cells may be involved in inflammatory arthritis induced by checkpoint inhibitors (CPI-IA). Our aim was to investigate the phenotype of circulating B cells in patients receiving CPI treatment and the relationship with CPI-IA.
Peripheral blood mononuclear cells were analyzed with flow-cytometry in CPI-IA patients and in patients who had not developed immune-related adverse events upon CPI (non-irAE). B cells were identified as CD19+ and divided into naïve (CD27-IgD+), memory (CD27+IgD+/-) and transitionals (CD10+CD24+CD38+/hi). Levels of the activation marker CD21 were also analyzed. Plasma levels of IL-6, IL-10 and BAFF were measured by ELISA. Non-parametric tests were used for comparisons.
Six CPI-IA and 7 non-irAE patients matched for age, gender and CPI treatment were included. CPI-IA patients displayed increased levels of circulating B cells (p=0.002) and of transitional B cells vs. non-irAE (median %, range: 7.8 (4.5-11.4) vs. 3.2 (1.6-4.3), p=0.007), while no remarkable changes were seen across other subsets. Transitional B cells significantly decreased when CPI-IA resolved (p=0.008). Levels of CD21 on transitional B cells were increased in CPI-IA vs. non-irAE (p=0.01). There were no significant differences in cytokine levels between patient groups. IL-10 tended to increase while IL-6 tended to decrease at CPI-IA resolution, yet not reaching significance. BAFF levels significantly increased from active to quiescent CPI-IA (p=0.02).
Transitional B cells are expanded in CPI-IA patients. BAFF increase may parallel their decrease at CPI-IA resolution. Monitoring of transitional B cells could facilitate early diagnosis and treatment of CPI-IA.