HELIOS Klinikum Krefeld, Center for Child and Adolescent Health, Krefeld, Germany.
Clin Immunol. 2010 May;135(2):183-92. doi: 10.1016/j.clim.2010.01.013. Epub 2010 Feb 20.
Combined immunodeficiencies with impaired numbers and function of T- and B-cells can be attributed to defects in the recombinase activating genes (RAG). The products of these genes, the RAG1 and 2 proteins, are key players in the V(D)J recombination process leading to the assembly of antigen receptor genes. Complete RAG deficiency (RAGD) with no V(D)J (<1% recombination activity of wild type) is associated with classical SCID and absence of T- and B-cells. In RAGD with residual V(D)J activity (>1% recombination activity of wild type), several clinical and immunological subtypes have been described: RAGD with skin inflammation and alphabeta T-cell expansion (classical Omenn syndrome), RAGD with skin inflammation and without T-cell expansion (incomplete Omenn syndrome), RAGD with gammadelta T-cell expansion and RAGD with granulomas. Engraftment of maternal T-cells can add to variation in phenotype. The potential role of epigenetic factors that influence the emergence of these phenotypes is discussed. Thorough assessment and interpretation of clinical and immunological findings will guide treatment modalities as intense as hematopoietic stem cell transplantation.
联合免疫缺陷伴有 T 细胞和 B 细胞数量和功能受损，可归因于重组激活基因（RAG）的缺陷。这些基因的产物，即 RAG1 和 RAG2 蛋白，是导致抗原受体基因组装的 V(D)J 重组过程中的关键因子。完全 RAG 缺陷（RAGD）无 V(D)J（野生型的重组活性<1%）与经典 SCID 和 T 细胞和 B 细胞缺失相关。在 RAGD 中有残留的 V(D)J 活性（野生型的重组活性>1%），已经描述了几种临床和免疫学亚型：伴有皮肤炎症和αβT 细胞扩增的 RAGD（经典 Omenn 综合征）、伴有皮肤炎症但无 T 细胞扩增的 RAGD（不完全 Omenn 综合征）、伴有γδT 细胞扩增的 RAGD 和伴有肉芽肿的 RAGD。母体 T 细胞的植入会增加表型的变异性。讨论了影响这些表型出现的表观遗传因素的潜在作用。彻底的临床和免疫学评估和解释将指导治疗方式，如造血干细胞移植等强烈的治疗方式。
