Division of Rheumatology, Catholic University of Sacred Heart, Rome, Italy.
Mol Med. 2011 Sep-Oct;17(9-10):901-9. doi: 10.2119/molmed.2011.00034. Epub 2011 May 13.
The aim of the present study was to determine whether different subsets of B cells characterize synovial fluid (SF) or synovial tissue (ST) of seropositive or seronegative rheumatoid arthritis (RA) with respect to the peripheral blood (PB). PB, SF and ST of 14 autoantibody (AB)-positive (rheumatoid factor [RF]-IgM, RF-IgA, anti-citrullinated peptide [CCP]), 13 negative RA and 13 no-RA chronic arthritides were examined for B-cell subsets (Bm1-Bm5 and IgD-CD27 classifications), zeta-associated protein kinase-70 (ZAP70) expression on B cells and cytokine levels (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, IL-6, IL-8 and monocyte chemotactic protein [MCP]-1). Synovial tissues were classified as aggregate and diffuse patterns. No differences were found in B-cell percentages or in subsets in PB and SF between AB(+) and AB(-) RA and no-RA. In both AB(+) and AB(-) RA (and no-RA), the percentage of CD19(+)/ZAP70(+) was higher in SF than in PB (AB(+): P = 0.03; AB(-): P = 0.01; no-RA: P = 0.01). Moreover, SF of both AB(+) and AB(-) RA (and no-RA) patients was characterized by a higher percentage of IgD-CD27(+) and IgD-CD27(-) B cells and lower percentage of IgD(+)CD27(-) (P < 0.05) B cells compared to PB. In SF, ZAP70 positivity is more represented in B cell CD27(+)/IgD(-)/CD38(-). The aggregate synovitis pattern was characterized by higher percentages of Bm5 cells in SF compared with the diffuse pattern (P = 0.05). These data suggest that no difference exists between AB(+) and AB(-) in B-cell subset compartmentalization. CD27(+)/IgD(-)/ZAP70(+) memory B cells accumulate preferentially in the joints of RA, suggesting a dynamic maturation of the B cells in this compartment.
本研究旨在确定针对外周血(PB),阳性或阴性血清类风湿关节炎(RA)的滑液(SF)或滑膜组织(ST)中是否存在不同的 B 细胞亚群。检测了 14 例自身抗体(AB)阳性(类风湿因子[RF]-IgM、RF-IgA、抗瓜氨酸肽[CCP])、13 例阴性 RA 和 13 例非 RA 慢性关节炎患者的 PB、SF 和 ST 的 B 细胞亚群(Bm1-Bm5 和 IgD-CD27 分类)、B 细胞上的 ζ 相关蛋白激酶-70(ZAP70)表达和细胞因子水平(白细胞介素[IL]-1β、肿瘤坏死因子 [TNF]-α、IL-6、IL-8 和单核细胞趋化蛋白 [MCP]-1)。滑膜组织分为聚集和弥漫两种模式。AB(+) 和 AB(-) RA 及非 RA 患者的 PB 和 SF 中 B 细胞百分比或亚群无差异。在 AB(+) 和 AB(-) RA(及非 RA)中,SF 中 CD19(+)/ZAP70(+)的百分比高于 PB(AB(+):P = 0.03;AB(-):P = 0.01;非 RA:P = 0.01)。此外,AB(+) 和 AB(-) RA(及非 RA)患者的 SF 还表现为 IgD-CD27(+)和 IgD-CD27(-)B 细胞的百分比更高,而 IgD(+)CD27(-)B 细胞的百分比更低(P < 0.05)。SF 中,ZAP70 阳性更多见于 CD27(+)/IgD(-)/CD38(-)B 细胞。聚集性滑膜炎模式 SF 中 Bm5 细胞的百分比高于弥漫性模式(P = 0.05)。这些数据表明,AB(+) 和 AB(-) 之间的 B 细胞亚群分区没有差异。CD27(+)/IgD(-)/ZAP70(+)记忆 B 细胞优先积聚在 RA 关节中,提示该分区中的 B 细胞动态成熟。