Multiparametric Profiling of Circulating Immune Cells Identifies an Expansion of CD25high Switched Memory B Cells in Osteoarthritis

Abstract

Objective: Osteoarthritis (OA) is a chronic, debilitating disease with no available disease-modifying drugs. Biomarker identification in patients with OA has hitherto been limited to serum proteins and bulk epigenomic feature identification.

Methods: Peripheral blood mononuclear cells (PBMCs) from 21 healthy donors, 17 patients with OA, and 10 patients with degenerative meniscal tears (DMTs) were immunophenotyped at single-cell resolution by mass cytometry by time-of-flight using a 29-marker panel to identify OA-associated features in the circulating immune cells. Single-cell RNA sequencing was used to discern mechanistic attributes of perturbed immune cell populations in OA.

Results: Comparison of the PBMCs of healthy donors and OA patients revealed distinct perturbations in OA. Although subsets of naive B cells were depleted, switched memory B cells were significantly expanded in OA, including a CD25^hiCXCR5^hiCD27⁺IgD^- subpopulation. Single-cell RNA sequencing revealed a dysfunction of interleukin 2/Stat5 and tumor necrosis factor 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.

Conclusion: A CD25^hi switched memory B cell population was identified to be a potential cellular biomarker for OA that can be detected in the early stages of OA in the readily accessible circulating blood cells.