Immune regulation in chronically transfused allo-antibody responder and nonresponder patients with sickle cell disease and ß-thalassemia major
Immune regulation in chronically transfused allo-antibody responder and nonresponder patients with sickle cell disease and ß-thalassemia major
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DOI：
10.1002/ajh.22167
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发表时间：
2011-12-01
影响因子：
12.8
通讯作者：
Yazdanbakhsh, Karina
中科院分区：
文献类型：
--
作者：
Bao, Weili;Zhong, Hui;Yazdanbakhsh, Karina
红细胞异体免疫是输血治疗的主要并发症。能够预测抗体应答者的宿主免疫标记物仍然缺乏描述。由于调节性T细胞(Tregs)在小鼠模型的同种异体免疫中起作用，我们分析了一组长期输血的镰状细胞病(SCD)患者(n=22)和重型β-地中海贫血(n=8)患者在有和没有同种异体抗体的情况下Treg间隔的情况。我们发现同种异体抗体应答者的Treg活性低于无应答者，就像在小鼠身上看到的那样。非同种异体免疫的SCD患者循环抗炎IL-10水平较高，而干扰素-γ水平较低。与无应答者相比，来自半数同种异体免疫患者的受激分选的CD4+细胞表达IL-4的频率增加，这表明在抗体应答者的亚群中存在扭曲的T辅助(Th)2体液免疫反应。所有患者的Th17反应均增强，提示潜在的炎症状态。虽然规模很小，但我们的研究表明，同种异体抗体反应者的免疫调节状态发生了变化，这可能有助于未来识别同种异体免疫的潜在分子风险因素。上午好。J.血醇。2011年。(C)2011年Wiley-Liss，Inc.
Red blood cell alloimmunization is a major complication of transfusion therapy. Host immune markers that can predict antibody responders remain poorly described. As regulatory T cells (Tregs) play a role in alloimmunization in mouse models, we analyzed the Treg compartment of a cohort of chronically transfused patients with sickle cell disease (SCD, n = 22) and beta-thalassemia major (n = 8) with and without alloantibodies. We found reduced Treg activity in alloantibody responders compared with nonresponders as seen in mice. Higher circulating anti-inflammatory IL-10 levels and lower IFN-gamma levels were detected in non-alloimmunized SCD patients. Stimulated sorted CD4+ cells from half of the alloimmunized patients had increased frequency of IL-4 expression compared with nonresponders, indicating a skewed T helper (Th) 2 humoral immune response in a subgroup of antibody responders. All patients had increased Th17 responses, suggesting an underlying inflammatory state. Although small, our study indicates an altered immunoregulatory state in alloantibody responders which may help future identification of potential molecular risk factors for alloimmunization. Am. J. Hematol. 2011. (c) 2011 Wiley-Liss, Inc.