Altered type 1 interferon responses in alloimmunized and nonalloimmunized patients with sickle cell disease.
Altered type 1 interferon responses in alloimmunized and nonalloimmunized patients with sickle cell disease.
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DOI：
10.1002/jha2.270
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发表时间：
2021-11
期刊：
影响因子：
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通讯作者：
Gibb DR
中科院分区：
文献类型：
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作者：
Madany E;Lee J;Halprin C;Seo J;Baca N;Majlessipour F;Hendrickson JE;Pepkowitz SH;Hayes C;Klapper E;Gibb DR
镰状细胞病（SCD）患者红细胞同种免疫的患病率很高。然而，对潜在的机制知之甚少。鉴于促炎性1型干扰素（IFNα/β）和干扰素刺激基因（ISG）促进小鼠同种异体免疫，我们假设IFNα/β可能有助于SCD患者同种异体免疫频率的增加。为了研究这一点，对既往输注过的SCD患者（有或无同种免疫）和种族匹配的健康对照的血液白细胞和外周血单核细胞（PBMC）中的ISG表达进行定量，并计算IFNα/β基因评分。与对照组相比，SCD白细胞和血浆细胞因子的IFNα/β基因评分升高（基因评分，p < 0.01）。在用IFNβ刺激后，与来自对照的经刺激的PBMC相比，来自SCD患者的分离的PBMC具有升高的ISG和IFNα/β基因评分（p < 0.05）。然而，同种免疫和非同种免疫患者之间，IFNβ刺激和未刺激的ISG表达没有显着差异。这些发现表明SCD患者表达IFNα/β基因特征，需要更大规模的研究来充分确定其在同种免疫中的作用。此外，SCD中IFNα/β应答改变的说明对IFNα/β介导的病毒免疫、对基于IFNα/β的治疗的应答和SCD的其他后遗症具有潜在意义。
Patients with sickle cell disease (SCD) have a high prevalence of RBC alloimmunization. However, underlying mechanisms are poorly understood. Given that proinflammatory type 1 interferons (IFNα/β) and interferon stimulated genes (ISGs) promote alloimmunization in mice, we hypothesized that IFNα/β may contribute to the increased frequency of alloimmunization in patients with SCD. To investigate this, expression of ISGs in blood leukocytes and peripheral blood mononuclear cells (PBMCs) of previously transfused SCD patients with or without alloimmunization and race‐matched healthy controls were quantified, and IFNα/β gene scores were calculated. IFNα/β gene scores of SCD leukocytes and plasma cytokines were elevated, compared to controls (gene score, p < 0.01). Upon stimulation with IFNβ, isolated PBMCs from patients with SCD had elevated ISGs and IFNα/β gene scores (p < 0.05), compared to stimulated PBMCs from controls. However, IFNβ‐stimulated and unstimulated ISG expression did not significantly differ between alloimmunized and non‐alloimmunized patients. These findings indicate that patients with SCD express an IFNα/β gene signature, and larger studies are needed to fully determine its role in alloimmunization. Further, illustration of altered IFNα/β responses in SCD has potential implications for IFNα/β‐mediated viral immunity, responses to IFNα/β‐based therapies, and other sequelae of SCD.