Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.
Arthritis Rheumatol. 2018 Apr;70(4):606-615. doi: 10.1002/art.40410. Epub 2018 Mar 25.
To investigate whether abnormalities in B cell subsets in patients with juvenile idiopathic arthritis (JIA) correlate with clinical features and response to treatment.
A total of 109 patients diagnosed as having oligoarticular JIA or polyarticular JIA were enrolled in the study. B cell subsets in peripheral blood and synovial fluid were analyzed by flow cytometry.
Switched memory B cells were significantly increased in patients compared to age-matched healthy controls (P < 0.0001). When patients were divided according to age at onset of JIA, in patients with early-onset disease (presenting before age 6 years) the expansion in switched memory B cells was more pronounced than that in patients with late-onset disease and persisted throughout the disease course. In longitudinal studies, during methotrexate (MTX) treatment, regardless of the presence or absence of active disease, the number of switched memory B cells increased significantly (median change from baseline 36% [interquartile range {IQR} 15, 66]). During treatment with MTX plus tumor necrosis factor inhibitors (TNFi), in patients maintaining disease remission, the increase in switched memory B cells was significantly lower than that in patients who experienced active disease (median change from baseline 4% [IQR -6, 32] versus 41% [IQR 11, 73]; P = 0.004). The yearly rate of increases in switched memory B cells was 1.5% in healthy controls, 1.2% in patients who maintained remission during treatment with MTX plus TNFi, 4.7% in patients who experienced active disease during treatment with MTX plus TNFi, and ~4% in patients treated with MTX alone.
Switched memory B cells expand during the disease course at a faster rate in JIA patients than in healthy children. This increase is more evident in patients with early-onset JIA. TNFi treatment inhibits this increase in patients who achieve and maintain remission, but not in those with active disease.
研究幼年特发性关节炎（JIA）患者 B 细胞亚群的异常是否与临床特征和治疗反应相关。
共纳入 109 例被诊断为寡关节型 JIA 或多关节型 JIA 的患者。通过流式细胞术分析外周血和滑液中的 B 细胞亚群。
与年龄匹配的健康对照组相比，患者的转换记忆 B 细胞明显增加（P<0.0001）。当根据 JIA 的发病年龄对患者进行分组时，在发病年龄早于 6 岁的患者中，转换记忆 B 细胞的扩增比发病年龄晚的患者更为明显，且在整个疾病过程中持续存在。在纵向研究中，无论是否存在活动性疾病，在接受甲氨蝶呤（MTX）治疗时，转换记忆 B 细胞的数量均显著增加（从基线中位数变化 36%[四分位距 {IQR} 15，66%]）。在 MTX 联合肿瘤坏死因子抑制剂（TNFi）治疗时，对于维持疾病缓解的患者，转换记忆 B 细胞的增加明显低于发生活动性疾病的患者（从基线中位数变化 4%[IQR -6，32]与 41%[IQR 11，73]；P=0.004）。在健康对照组中，转换记忆 B 细胞的年增长率为 1.5%，在 MTX 联合 TNFi 治疗期间维持缓解的患者中为 1.2%，在 MTX 联合 TNFi 治疗期间发生活动性疾病的患者中为 4.7%，在单独接受 MTX 治疗的患者中约为 4%。
JIA 患者的疾病过程中，转换记忆 B 细胞的扩增速度快于健康儿童。这种增加在发病年龄早的患者中更为明显。TNFi 治疗可抑制缓解并维持缓解患者的这种增加，但不能抑制活动性疾病患者的增加。
