Multiparametric Profiling of Circulating Immune Cells Identifies an Expansion of CD25^high Switched Memory B Cells in Osteoarthritis.

Abstract

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. 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. 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. 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.