A variant of SCID with specific immune responses and predominance of γδ T cells
A variant of SCID with specific immune responses and predominance of γδ T cells
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DOI：
10.1172/jci25221
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发表时间：
2005-11-01
影响因子：
15.9
通讯作者：
Fisch, P
中科院分区：
文献类型：
--
作者：
Ehl, S;Schwarz, K;Fisch, P
我们在这里描述了一位临床和分子诊断为重组酶激活基因1缺陷(RAG1缺陷)SCID的患者，尽管B细胞数量很少，但他仍产生了特异性抗体。检测了记忆B细胞，不仅产生了针对某些疫苗和感染的抗体，还产生了针对自身抗原的抗体。患者表达UP TCR的寡克隆T细胞水平严重降低，但表达GMATβTCR的T细胞数量出人意料地正常。克隆水平分析和γ-Delta T细胞TCR互补决定区-3分型揭示了一个多样化的寡克隆谱系，其中以表达γ-4-Delta-3TCR的细胞为主。几个Gamma Delta T细胞克隆显示出对CMV感染细胞的反应性。这些观察结果与伽马三角洲T细胞优势的两种不相互排斥的解释是一致的：发育优势和感染引发的、抗原驱动的外周扩张。患者携带R561H RAG1纯合低态突变，导致V(D)J重组减少，但缺乏Omenn综合征的所有临床特征。这份报告描述了一种新的RAG缺乏症的表型，并表明形成特异性抗体的能力不排除SCID的诊断。
We describe here a patient with a clinical and molecular diagnosis of recombinase activating gene 1-deficient (RAG1-deficient) SCID, who produced specific antibodies despite minimal B cell numbers. Memory B cells were detected and antibodies were produced not only against some vaccines and infections, but also against autoantigens. The patient had severely reduced levels of oligoclonal T cells expressing the up TCR but surprisingly normal numbers of T cells expressing the gamma delta TCR. Analysis at a clonal level and TCR complementarity-determining region-3 spectratyping for gamma delta T cells revealed a diversified oligoclonal repertoire with predominance of cells expressing a gamma 4-delta 3 TCR. Several gamma delta T cell clones displayed reactivity against CMV-infected cells. These observations are compatible with 2 non-mutually exclusive explanations for the gamma delta T cell predominance: a developmental advantage and infection-triggered, antigen-driven peripheral expansion. The patient carried the homozygous hypomorphic R561H RAG1 mutation leading to reduced V(D)J recombination but lacked all clinical features characteristic of Omenn syndrome. This report describes a new phenotype of RAG deficiency and shows that the ability to form specific antibodies does not exclude the diagnosis of SCID.