Division of Rheumatology, Institute of Rheumatology and Affine Sciences (IRSA), School of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
J Rheumatol. 2012 Dec;39(12):2276-85. doi: 10.3899/jrheum.120153. Epub 2012 Sep 15.
To define the role of ZAP-70+ B cells (CD19+/ZAP-70+) as a biomarker of response to B cell depletion therapy (BCDT), their relationship with clinical outcome, and their behavior during repopulation of peripheral blood in patients with rheumatoid arthritis (RA).
Thirty-one patients with RA underwent BCDT and were followed for 12 months. Disease activity was assessed with the European League Against Rheumatism (EULAR) criteria. Cytofluorimetric analysis of peripheral blood B cell subsets at baseline and at 6- and 12-month intervals after BCDT was performed using surface markers (CD45, CD3, CD56, CD19, IgD, CD38, CD27) and intracellular ZAP-70.
A moderate/good EULAR response was achieved in 66.6% of the RA cohort. The baseline percentage of CD19+/ZAP-70+ cells was lower in good responder patients (1.8% ± 1.7%) compared to poor responders (5.6% ± 4.9%; p = 0.02). A decrease of plasmablasts (IgD-CD27+CD38+) and pre-switch memory (IgD+CD27+) B cells occurred after BCDT. Recovery of B cells in peripheral blood after the first course of BCDT was characterized by the reappearance of B cell subtypes that showed a naive, activated phenotype, coupled with a decrease in memory cells. B cells carrying intracytoplasmic ZAP-70 increased significantly from the baseline value of 4.4% ± 4.5% to 12.4% ± 9.2% (p = 0.001) at the 6-month and to 9.4% ± 6.4% (p = 0.002) at the 12-month followup.
Baseline percentage of CD19+/ZAP-70+ cells is associated with the clinical outcome after BCDT in patients with RA. Depletion of plasmablasts and pre-switch memory B cells and increase of CD19+/ZAP-70+ cells are features of the recovery of the B cell pool after BCDT.
确定 ZAP-70+B 细胞（CD19+/ZAP-70+）作为 B 细胞耗竭治疗（BCDT）反应生物标志物的作用，它们与临床结果的关系，以及它们在类风湿关节炎（RA）患者外周血再增殖过程中的行为。
31 例 RA 患者接受 BCDT 治疗，并随访 12 个月。采用欧洲抗风湿病联盟（EULAR）标准评估疾病活动度。采用表面标志物（CD45、CD3、CD56、CD19、IgD、CD38、CD27）和细胞内 ZAP-70 对 BCDT 前后 6 个月和 12 个月的外周血 B 细胞亚群进行流式细胞仪分析。
RA 队列中 66.6%的患者达到了中度/良好的 EULAR 反应。与反应不佳的患者（5.6%±4.9%）相比，良好反应者的 CD19+/ZAP-70+细胞的基线百分比较低（1.8%±1.7%；p=0.02）。BCDT 后，浆母细胞（IgD-CD27+CD38+）和前转换记忆（IgD+CD27+）B 细胞减少。BCDT 后第一疗程外周血 B 细胞的恢复表现为出现幼稚、激活表型的 B 细胞亚群，同时记忆细胞减少。胞质内 ZAP-70 阳性的 B 细胞从基线值 4.4%±4.5%显著增加至 6 个月时的 12.4%±9.2%（p=0.001），并在 12 个月时增加至 9.4%±6.4%（p=0.002）。
RA 患者 BCDT 后，基线 CD19+/ZAP-70+细胞百分比与临床结果相关。浆母细胞和前转换记忆 B 细胞的耗竭以及 CD19+/ZAP-70+细胞的增加是 BCDT 后 B 细胞库恢复的特征。
