Study on the mechanism of autoimmunity and malignancy developed in primary immunodeficiency

对原发性免疫缺陷(PID)患者常见的自身免疫和恶性病变机制进行了研究。DNA损伤反应受损的患者，如共济失调、毛细血管扩张症(AT)和Mre11缺乏症，表现为DNA损伤处理缺陷所致的染色体异常。AT患者也显示T细胞发育缺陷。ICOS缺乏症患者外周血中T细胞无能被正确执行，表现为自身免疫。在大约50%的CVID患者中观察到TCR V曲目的偏斜使用。这些发现表明，在PID患者中存在多种自身免疫紊乱和恶性的机制。

We studied on the mechanism of autoimmunity and malignancy frequently observed in patients with primary immunodeficiency (PID). Patients with impaired DNA damage response such as ataxia telangiectasia (AT) and Mre11 deficiency showed chromosomal abnormality caused by defect in DNA damage processing. AT patients showed defective T-cell development as well. T-cell anergy was not properly executed in lymphocytes from ICOS deficiency showing autoimmunity. Skewed TCR V repertoire usage was observed in ～50% of CVID patients. These findings suggest the presence of various mechanism underling autoimmune disorder and malignancy in PID patients.