Blood:血红色可抑制SCD患者的体液B细胞反应调控同种免疫风险

2020-11-25 Nebula-Qin MedSci原创

红细胞同种免疫仍然是镰状细胞疾病(SCD)中安全有效输血的障碍,但相关的危险因素仍然未完全明确。血管内溶血,是SCD的标志,可释放具有有效免疫调节活性的血红素。然而,血管内溶血对SCD体液反应(特别是

红细胞同种免疫仍然是镰状细胞疾病(SCD)中安全有效输血的障碍,但相关的危险因素仍然未完全明确。血管内溶血,是SCD的标志,可释放具有有效免疫调节活性的血红素。然而,血管内溶血对SCD体液反应(特别是同种免疫)的作用也尚不清楚。

Mouli等发现,无细胞血红素通过抑制DOCK8/STAT3信号通路来抑制人B浆母细胞/浆细胞分化;DOCK8/STAT3信号通路对B细胞活化以及通过其酶促副产物一氧化碳和胆绿素上调血红素加氧酶1(HO-1)均至关重要。

血红色对B细胞激活的影响

非同种免疫的SCD B细胞可被外源血红素抑制,而同种免疫的B细胞对血红素抑制无反应,并容易分化成浆细胞。与B细胞对溶血的差异反应一致,研究人员发现,与同种免疫的SCD患者相比,未经同种免疫的SCD患者的DOCK8的B细胞基础水平升高,HO-1介导的活化B细胞抑制更高。

同种免疫和非同种免疫在不同浓度血红素和奎宁处理下的浆细胞变化

为了克服同种免疫的B细胞对血红素的不敏感性,研究人员筛选了几种血红素结合分子,并将奎宁确定为B细胞活性的有效抑制剂,从而逆转了同种免疫患者对血红素抑制的抵抗力。奎宁对B细胞的抑制作用仅在血红素存在下并通过HO-1诱导发生。

总而言之,这些数据表明,溶血可以抑制体液B细胞应答,而B细胞对血红素的反应可能是SCD患者同种免疫风险的决定因素。通过恢复B细胞对血红素的敏感性,奎宁可能具有预防和抑制SCD患者同种免疫的治疗潜力。

原始出处:

Mouli Pal, et al. Hemolysis Inhibits Humoral B Cell Responses and Modulates Alloimmunization Risk in Patients with Sickle Cell Disease. Blood. November 5, 2020.

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