Sahu Neety, Bedi Yudhishtar Singh, Grandi Fiorella, Maloney William J, Chu Constance R, Bhutani Nidhi
Stanford University, Stanford, California.
Gladstone Institutes for Neurological Disease and Data Science and Biotechnology, Gladstone Institutes and University of California at San Francisco.
Arthritis Rheumatol. 2025 Apr 14. doi: 10.1002/art.43186.
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 CD25CXCR5CD27IgD subpopulation. Single-cell RNA sequencing revealed a dysfunction of interleukin 2/Stat5 and tumor necrosis factor signaling in the CD25 switched memory B cells in OA. A similar expansion of CD25 switched memory B cells was observed in patients with DMT, a population at enhanced risk for OA.
A CD25 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.
骨关节炎（OA）是一种慢性致残性疾病，目前尚无改善病情的药物。迄今为止，OA患者的生物标志物鉴定仅限于血清蛋白和整体表观基因组特征鉴定。
使用包含29种标志物的面板，通过飞行时间质谱流式细胞术对来自21名健康供体、17名OA患者和10名退行性半月板撕裂（DMT）患者的外周血单个核细胞（PBMC）进行单细胞分辨率的免疫表型分析，以确定循环免疫细胞中与OA相关的特征。采用单细胞RNA测序来识别OA中受干扰免疫细胞群体的机制属性。
健康供体和OA患者的PBMC比较显示OA存在明显的扰动。虽然初始B细胞亚群减少，但在OA中转换记忆B细胞显著扩增，包括一个CD25CXCR5CD27IgD亚群。单细胞RNA测序显示OA中CD25转换记忆B细胞白细胞介素2/信号转导及转录激活因子5和肿瘤坏死因子信号传导功能失调。在DMT患者中观察到类似的CD25转换记忆B细胞扩增，DMT患者是OA风险增加的人群。
CD25转换记忆B细胞群体被确定为OA的潜在细胞生物标志物，可在OA早期阶段在外周血中易于获取的循环血细胞中检测到。
