Defective regulatory B-cell compartment in patients with immune thrombocytopenia
Defective regulatory B-cell compartment in patients with immune thrombocytopenia
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DOI：
10.1182/blood-2012-05-432575
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发表时间：
2012-10-18
期刊：
影响因子：
20.3
通讯作者：
Yazdanbakhsh, Karina
中科院分区：
文献类型：
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作者：
Li, Xiaojuan;Zhong, Hui;Yazdanbakhsh, Karina
产生抗血小板自身抗体的B淋巴细胞在自身免疫性血小板减少症(ITP)中起主要作用。然而，某些B细胞，包括人类CD19(+)CD24(Hi)CD38(Hi)亚群，具有部分由IL-10介导的调节功能。在一组血小板计数低的慢性ITP患者中，非脾切除患者外周血中CD19(+)CD24(Hi)CD38(Hi)的频率较低(P=0.03)。血小板数为50×10(9)个/L的ITP患者外周血中CD19(+)亚群活化后IL-10表达减少(P<0.05)，活化B细胞对单核细胞表达肿瘤坏死因子-α的抑制作用减少(P=.001)，提示ITP患者调节性B细胞抑制单核细胞活化的能力受损。有趣的是，在未切除脾的患者中，经促血小板药物治疗后血小板计数升高的患者，CD19(+)CD24(Hi)CD38(Hi)B细胞的频率较治疗前增加(P=0.02)。总之，这些数据表明，作为慢性ITP患者免疫调节的额外缺陷，调节B细胞室受损，对血小板生成治疗的应答者可能会恢复这种缺陷。(血。2012；120(16)：3318-3325)
B lymphocytes producing antiplatelet autoantibodies play a major role in autoimmune thrombocytopenia (ITP). However, certain B cells, including the human CD19(+)CD24(hi)CD38(hi) subpopulation, possess regulatory functions mediated partly by IL-10. In a cohort of chronic ITP patients with low platelet counts who consisted of patients off treatment, we found a lower frequency of CD19(+)CD24(hi)CD38(hi) in the peripheral compartment of nonsplenectomized patients (P = .03). IL-10 expression after activation was decreased in all ITP circulating CD19(+) subpopulations (P < .03), and inhibition of monocyte TNF-alpha expression by activated B cells was reduced in patients with platelet numbers of < 50 x 10(9) cells/L (P = .001), indicating that regulatory B cells of patients with ITP are functionally impaired in their ability to dampen monocyte activation. Interestingly, in nonsplenectomized patients whose platelet counts were elevated after treatment with thrombopoietic agents, the frequency of CD19(+)CD24(hi)CD38(hi) B cells was increased compared with those before treatment (P = .02). Altogether, these data indicate a compromised regulatory B-cell compartment as an additional defect in immune regulation in patients with chronic ITP that may be restored in responders to thrombopoietic treatment. (Blood. 2012;120(16):3318-3325)