重组激活基因突变与免疫缺陷病表型多样性

The diverse phenotypes of RAG mutation associated immunodeficiency

重组激活基因（ recombination activating gene, RAG）突变导致一系列严重的免疫缺陷病，包括重症联合免疫缺陷（ severe combined immunodeficiency, SCID）、Omenn综合征以及多种其他特殊表型。不同患者因RAG分子表达受影响程度的差异而表现出复杂多样的免疫表型、组织病理学改变和临床表现。RAG完全缺陷分为典型SCID和母源T细胞输入型SCID。RAG残留缺陷包括典型Omenn综合征、非典型Omenn综合征、肉芽肿性炎症、18T细胞优势扩增型以及母源T细胞植入。患者的淋巴细胞分化发育受到完全或者部分阻断，导致反复感染，并且常伴随自身免疫反应，严重威胁生命。该文对RAG免疫缺陷的各种复杂表型进行归纳，为该疾病的正确诊断、针对性治疗以及发病机制研究提供参考。

RAG mutations cause a spectrum of severe immunodeficiencies ranging from classical severe combined immunodeficiency （SCID） and Omenn syndrome to an increasing number of peculiar phenotypes. Based on the distinct levels of RAG expression in various patients, their immunopbenotypes, histopathological findings and clinical manifestations are diverse. The subtypes of RAG-defect diseases have been described as classical SCID, SCID with maternal T cells, classical Omenn syndrome, atypical Omenn syndrome, granuloma- tous inflammation, predominance/expansion of ~/^-T ceils and maternal T-cell engraftment. The complete failure or partial blockage of lymphocyte development and differentiation can cause repeated infections with autoimmune reactions frequently, and may be lethal. Thorough assessment and interpretation of various phenotypes will guide accurate diagnosis, definitive treatment and the mechanism research.