Multi‐parametric profiling of circulating immune cells identifies an expansion of CD25hi switched memory B cells in Osteoarthritis

Objective Osteoarthritis (OA) is a chronic, debilitating disease with no available disease‐modifying drugs. Biomarker identification in OA patients has hitherto been limited to serum proteins and bulk epigenomic feature identification. Methods Peripheral blood mononuclear cells (PBMC) from 21 healthy donors, 17 OA patients, and 10 patients with degenerative meniscal tears (DMT) were immunophenotyped at single‐cell resolution by mass cytometry by time‐of‐flight (cyTOF) using a 29‐marker panel to identify OA‐associated features in the circulating immune cells. Single‐cell RNA sequencing was utilized to discern mechanistic attributes of perturbed immune cell populations in OA. Results Comparison of healthy donors and OA patients’ PBMC revealed distinct perturbations in OA. While subsets of naive B cells were depleted, switched memory B cells were significantly expanded in OA including a CD25 hi CXCR5 hi CD27 + IgD ‐ subpopulation. Single cell‐RNA sequencing revealed a dysfunction of IL2/Stat3 and TNF signaling in the CD25 hi switched memory B cells in OA. A similar expansion of CD25 hi switched memory B cells was observed in patients with DMT, a population at enhanced risk for OA. Conclusions A CD25 hi switched memory B cell population was identified to be a potential cellular biomarker for OA that can be detected in early stages of OA in the readily accessible circulating blood cells. image