University of Rochester Medical Center, Rochester, New York.
Medical University of South Carolina, Charleston.
Arthritis Rheumatol. 2022 Feb;74(2):200-211. doi: 10.1002/art.41941. Epub 2021 Dec 27.
B cells can become activated in germinal center (GC) reactions in secondary lymphoid tissue and in ectopic GCs in rheumatoid arthritis (RA) synovium that may be tumor necrosis factor (TNF) and lymphotoxin (LT) dependent. This study was undertaken to characterize the peripheral B cell compartment longitudinally during anti-TNF therapy in RA.
Participants were randomized in a 2:1 ratio to receive standard dosing regimens of etanercept (n = 43) or adalimumab (n = 20) for 24 weeks. Eligible participants met the American College of Rheumatology 1987 criteria for RA, had clinically active disease (Disease Activity Score in 28 joints >4.4), and were receiving stable doses of methotrexate. The primary mechanistic end point was the change in switched memory B cell fraction from baseline to week 12 in each treatment group.
B cell subsets remained surprisingly stable over the course of the study regardless of treatment group, with no significant change in memory B cells. Blockade of TNF and LT with etanercept compared to blockade of TNF alone with adalimumab did not translate into significant differences in clinical response. The frequencies of multiple activated B cell populations, including CD21- double-negative memory and activated naive B cells, were higher in RA nonresponders at all time points, and CD95+ activated B cell frequencies were increased in patients receiving anti-TNF treatment in the nonresponder group. In contrast, frequencies of transitional B cells-a putative regulatory subset-were lower in the nonresponders.
Overall, our results support the notion that peripheral blood B cell subsets are remarkably stable in RA and not differentially impacted by dual blockade of TNF and LT with etanercept or single blockade of TNF with adalimumab. Activated B cells do associate with a less robust response.
B 细胞可在次级淋巴组织的生发中心（GC）反应中和类风湿关节炎（RA）滑膜中的异位 GC 中被激活，这些 GC 可能依赖于肿瘤坏死因子（TNF）和淋巴毒素（LT）。本研究旨在描述在 RA 患者接受抗 TNF 治疗过程中，外周 B 细胞群的纵向变化。
参与者按照 2:1 的比例随机分配，接受依那西普（n=43）或阿达木单抗（n=20）的标准剂量治疗方案，治疗 24 周。符合条件的参与者符合美国风湿病学会 1987 年 RA 标准，疾病处于活动期（28 个关节疾病活动评分>4.4），并接受稳定剂量的甲氨蝶呤治疗。主要的机制终点是每个治疗组从基线到第 12 周时转换记忆 B 细胞亚群的变化。
无论治疗组如何，B 细胞亚群在整个研究过程中都保持惊人的稳定，记忆 B 细胞没有明显变化。与单独阻断 TNF 相比，依那西普同时阻断 TNF 和 LT 并不能转化为临床反应的显著差异。在所有时间点，RA 无反应者的多种活化 B 细胞群体（包括 CD21-双阴性记忆和活化的幼稚 B 细胞）的频率更高，而在无反应者组接受抗 TNF 治疗的患者中，CD95+活化 B 细胞的频率增加。相比之下，无反应者的过渡 B 细胞（一种假定的调节亚群）的频率较低。
总体而言，我们的结果支持这样一种观点，即在 RA 中，外周血 B 细胞亚群非常稳定，依那西普同时阻断 TNF 和 LT 或阿达木单抗单独阻断 TNF 对其影响无差异。活化的 B 细胞与反应较弱相关。
