Idiopathic CD4+ T lymphopenia without autoimmunity or granulomatous disease in the slipstream of RAG mutations
Idiopathic CD4+ T lymphopenia without autoimmunity or granulomatous disease in the slipstream of RAG mutations
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DOI：
10.1182/blood-2011-01-329052
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发表时间：
2011-06-02
期刊：
影响因子：
20.3
通讯作者：
van der Burg, Mirjam
中科院分区：
文献类型：
--
作者：
Kuijpers, Taco W.;IJspeert, Hanna;van der Burg, Mirjam
一个女孩在儿童时期表现为一个单一的广泛的水痘和中度，虽然复发性肺炎的存在特发性CD 4（+）T淋巴细胞减少症（ICL）。她的临床状况在过去10年中保持稳定，没有感染、任何肉芽肿性疾病或自身免疫。免疫表型分析表明幼稚T和B细胞明显减少，具有完整的增殖能力。体内免疫的抗体反应性是正常的。T细胞受体-V β库是多克隆的，具有非常低含量的T细胞受体切除环（TRECs）。在B细胞中，κ缺失重组切除环（KREC）也异常。两者都反映了广泛的体内增殖。患者来源的CD 34（+）造血干细胞不能重新填充RAG 2（-/-）IL 2 R γ c（-/-）小鼠，表明该缺陷的淋巴起源。我们在RAG 1中发现了2个新的错义突变（p.Arg474Cys和p.Leu506Phe），导致RAG活性降低。该报告给出了ICL的第一个遗传线索，并将RAG突变的临床谱从严重的免疫缺陷扩展到几乎正常的情况。（血。2011; 117（22）：5892-5896）
A girl presented during childhood with a single course of extensive chickenpox and moderate albeit recurrent pneumonia in the presence of idiopathic CD4(+) T lymphocytopenia (ICL). Her clinical condition remained stable over the past 10 years without infections, any granulomatous disease, or autoimmunity. Immunophenotyping demonstrated strongly reduced naive T and B cells with intact proliferative capacity. Antibody reactivity on in vivo immunizations was normal. T-cell receptor-V beta repertoire was polyclonal with a very low content of T-cell receptor excision circles (TRECs). Kappa-deleting recombination excision circles (KRECs) were also abnormal in the B cells. Both reflect extensive in vivo proliferation. Patient-derived CD34(+) hematopoietic stem cells could not repopulate RAG2(-/-)IL2R gamma c(-/-) mice, indicating the lymphoid origin of the defect. We identified 2 novel missense mutations in RAG1 (p.Arg474Cys and p.Leu506Phe) resulting in reduced RAG activity. This report gives the first genetic clue for ICL and extends the clinical spectrum of RAG mutations from severe immune defects to an almost normal condition. (Blood. 2011; 117(22): 5892-5896)