Kumaki S, Villa A, Asada H, Kawai S, Ohashi Y, Takahashi M, Hakozaki I, Nitanai E, Minegishi M, Tsuchiya S
Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Blood. 2001 Sep 1;98(5):1464-8. doi: 10.1182/blood.v98.5.1464.
Mutations of the RAG1 or RAG2 protein that eliminate their recombination activity result in T-B-severe combined immunodeficiency (SCID), whereas mutations retaining partial recombination activity lead to Omenn syndrome, a peculiar SCID characterized by increased host T cells and absence of circulating B cells. The prognosis of this disease is fatal, unless hematopoietic stem cell transplantation is performed. This study reports a case of atypical SCID, carrying RAG1 mutations. The patient survived for 6 years without hematopoietic stem cell transplantation. The missense mutation, tested by in vivo recombination assay, revealed residual recombination activity. By the age of 5 years, the patient developed host B cells, but not T cells, possibly due to engrafted maternal T cells. In addition, the host B cells were able to produce antibodies, including anti-herpes simplex virus-antibodies. The fact that host B cells could produce antibodies in this patient could explain not only the mild phenotype observed but also, at least in part, how patients with Omenn syndrome produce immunoglobulin E and sometimes immunoglobulin M, as the same missense mutation of RAG1 gene has been reported in a patient with Omenn syndrome.
RAG1或RAG2蛋白的突变若消除其重组活性，会导致T-B重症联合免疫缺陷（SCID），而保留部分重组活性的突变则会引发欧门综合征，这是一种特殊类型的SCID，其特征为宿主T细胞增多且循环B细胞缺失。这种疾病的预后是致命的，除非进行造血干细胞移植。本研究报告了一例携带RAG1突变的非典型SCID病例。该患者未经造血干细胞移植存活了6年。通过体内重组试验检测的错义突变显示具有残余重组活性。到5岁时，患者出现了宿主B细胞，但未出现T细胞，这可能是由于母体T细胞植入所致。此外，宿主B细胞能够产生抗体，包括抗单纯疱疹病毒抗体。该患者的宿主B细胞能够产生抗体这一事实，不仅可以解释所观察到的轻度表型，而且至少部分地解释了欧门综合征患者如何产生免疫球蛋白E，有时还产生免疫球蛋白M，因为在一名欧门综合征患者中也报道了相同的RAG1基因错义突变。
