Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Front Immunol. 2022 Apr 4;13:866582. doi: 10.3389/fimmu.2022.866582. eCollection 2022.
AIOLOS is encoded by and is a member of the IKAROS zinc finger transcription factor family. Heterozygous missense variants in the second zinc finger of AIOLOS have recently been reported to be found in the families of patients with inborn errors of immunity. The AIOLOS variant was identified in patients with B-lymphopenia and familial Epstein-Barr virus-associated lymphoma. Early B-cell progenitors were significantly reduced in the bone marrow of patients with AIOLOS. Another variant, AIOLOS was identified in the patients presented with hypogammaglobulinemia, susceptibility to pneumonia, and chronic lymphocytic leukemia. Patients with AIOLOS had mostly normal B cell counts but showed increased levels of CD21 B cells, decreased CD23 expression, and abrogated CD40 response. Both variants were determined to be loss-of-function. Mouse models harboring the corresponding patient's variants recapitulated the phenotypes of the patients. AIOLOS is therefore a novel disease-causing gene in human adaptive immune deficiency.
AIOLOS 由 编码，是 IKAROS 锌指转录因子家族的成员。最近报道，AIOLOS 第二个锌指中的杂合错义变异存在于免疫固有缺陷患者的家族中。AIOLOS 变异在伴有 B 淋巴细胞减少和家族性 EBV 相关淋巴瘤的患者中被发现。AIOLOS 患者的骨髓中早期 B 细胞前体明显减少。另一种变异 AIOLOS 存在于表现为低丙种球蛋白血症、易患肺炎和慢性淋巴细胞白血病的患者中。AIOLOS 患者的 B 细胞计数大多正常，但表现为 CD21 B 细胞水平升高、CD23 表达降低和 CD40 反应缺失。这两种变异均被确定为失功能。携带相应患者变异的小鼠模型重现了患者的表型。因此，AIOLOS 是人类适应性免疫缺陷的一种新的致病基因。
