We report the case of a patient with X-linked severe combined immunodeficiency (X-SCID) who survived for over 20 years without hematopoietic stem cell transplantation (HSCT) because of a somatic reversion mutation. An important feature of this rare case included the strategy to validate the pathogenicity of a variant of the IL2RG gene when the T and B cell lineages comprised only revertant cells. We studied the X-inactivation of sorted T cells from the mother to show that the pathogenic variant was indeed the cause of his SCID. One interesting feature was a progressive loss of B cells over 20 years. CyTOF (cytometry time of flight) analysis of bone marrow offered a potential explanation of the B cell failure, with expansions of progenitor populations that suggest a developmental block. Another interesting feature was that the patient bore extensive granulomatous disease and skin cancers that contained T cells, despite severe T cell lymphopenia in the blood. Finally, the patient had a few hundred T cells on presentation but his TCRs comprised a very limited repertoire, supporting the important conclusion that repertoire size trumps numbers of T cells.

我们报道了一名 X 连锁严重联合免疫缺陷 (X-SCID) 患者的病例，由于体细胞回复突变，在未进行造血干细胞移植 (HSCT) 的情况下存活了 20 多年。该罕见病例的一个重要特征包括当 T 细胞和 B 细胞谱系仅包含回复细胞时验证IL2RG基因变体的致病性的策略。我们研究了来自母亲的分选 T 细胞的 X 失活，以表明致病性变异确实是他 SCID 的原因。一个有趣的特征是 B 细胞在 20 年内逐渐丧失。骨髓的 CyTOF（细胞飞行时间）分析为 B 细胞衰竭提供了可能的解释，祖细胞群的扩张表明发育受阻。另一个有趣的特征是，尽管血液中 T 细胞淋巴细胞严重减少，但患者患有广泛的肉芽肿性疾病和含有 T 细胞的皮肤癌。最后，患者出现了数百个 T 细胞，但他的 TCR 包含非常有限的库，这支持了库大小胜过 T 细胞数量的重要结论。