Department of Internal Medicine, Division of Rheumatology, University of Patras Medical School, Patras, Greece.
Clin Immunol. 2011 Jul;140(1):8-17. doi: 10.1016/j.clim.2011.01.012. Epub 2011 Feb 2.
To dissect the mechanisms of anti-TNFα-induced autoimmunity we examined the phenotype and function of B cells from anti-TNFα-treated patients. Levels of Lyn, Syk, SHP-1, tyrosine 348 phospho-Syk (Y348-Syk) and tyrosine phosphorylated (P-Y) proteins were evaluated and B-cell-surface CD20, CD21 and CD5 were also assessed in 29 patients treated with TNF-α blockers. Following treatment, Lyn, but not Syk or SHP-1, significantly increased particularly in patients with spondyloarthropathies. Increased Lyn levels following treatment correlated with increased Lyn activity as evidenced by a 2.9-fold increase of Y348-Syk (a Lyn target). Peripheral B-cells from 56.3% of the patients displayed a tendency towards increased P-Y levels without any BCR-initiated activation during treatment. CD20, but not CD21, significantly increased in patients with rheumatoid arthritis. Circulating CD5+ B-cells were also significantly expanded during treatment. Our findings suggest that B cells in anti-TNFα-treated patients display functional and phenotypical aberrations that may enhance our understanding of TNF-α blocker-induced autoimmunity.
为了剖析抗 TNF-α 诱导自身免疫的机制，我们研究了接受抗 TNF-α 治疗的患者的 B 细胞表型和功能。在 29 名接受 TNF-α 阻滞剂治疗的患者中，评估了 Lyn、Syk、SHP-1、酪氨酸 348 磷酸化 Syk（Y348-Syk）和酪氨酸磷酸化（P-Y）蛋白的水平，并且还评估了 B 细胞表面 CD20、CD21 和 CD5。治疗后，Lyn 显著增加，但 Syk 或 SHP-1 没有增加，尤其是在患有脊柱关节病的患者中。治疗后 Lyn 水平的增加与 Lyn 活性的增加相关，这表现为 Y348-Syk（Lyn 的靶标）增加了 2.9 倍。56.3%的患者的外周 B 细胞在治疗期间显示出 P-Y 水平增加的趋势，但没有任何 BCR 起始的激活。类风湿关节炎患者的 CD20 而非 CD21 显著增加。循环 CD5+B 细胞在治疗期间也显著扩增。我们的发现表明，接受抗 TNF-α 治疗的患者的 B 细胞显示出功能和表型异常，这可能有助于我们理解 TNF-α 阻滞剂诱导的自身免疫。
