Immunophenotyping of Patients With Rheumatoid Arthritis Reveals Difference in CD27 ⁺ IgD ⁺ Unswitched Memory B Cell Profiles

<b>Objectives:</b> Over the past decades, the prevalence of noncommunicable diseases has surged significantly, including the systemic autoimmune disorder rheumatoid arthritis (RA). Despite extensive research and advancement of RA therapy, effective prevention strategies or cures remain elusive, and the mechanisms underlying RA pathogenesis unclear. It is crucial to gain deeper insights into RA pathophysiology. The objective of this study is to provide a comprehensive immunophenotyping of patients with RA. <b>Methods:</b> We generated and analyzed deep immunophenotyping data from 52 patients with RA and 47 healthy controls (HCs). Whole blood samples were stained with extracellular markers, and intracellular antibodies and analyzed for 32 different cell markers using mass cytometry by time of flight. The acquired data was analyzed by both manual and automatic unsupervised tools and subsequently complemented with anthropometric data and clinical-laboratory parameters. <b>Results:</b> We observed a significant disparity in immune cell profiles between patients with RA and HC, notably a reduced frequency of CD27⁺IgD⁺ unswitched memory B (_mB) cells in patients with RA (<i>p</i>-value < 0.01), with the disease RA being the primary and only significant factor explaining up to 17.9% of the variance of these cells. <b>Conclusion:</b> Our results reveal, for the first time, that a reduced frequency of unswitched _mB cells in patients with RA is the only significant abnormality distinguishing patients with RA from HC in a complex immunophenotyping panel of 72 different cell populations. This provides important information to further individualize various interventions and possibly help to design novel therapeutic interventions.