Allergy Asthma Proc. 2024 Sep 1;45(5):326-331. doi: 10.2500/aap.2024.45.240028.
Genetically determined defects of T-cell development comprise a heterogeneous group of conditions characterized by peripheral T-cell lymphopenia due to impaired intrathymic differentiation of T-cell progenitors. Collectively, these conditions are typically referred to as severe combined immune deficiency (SCID). In some cases (leaky SCID), residual function of the defective gene allows partial T-cell development. The vast majority of SCID disorders are due to genetic defects that affect the T-cell differentiation potential of hematopoietic stem cells, through a variety of mechanisms. However, some forms of SCID reflect impaired development or function of thymic stromal cells. A lack of peripheral T cells leads to increased susceptibility to severe infections since early in life. SCID is inevitably fatal unless immune reconstitution is achieved, most often through hematopoietic cell transplantation. Enzyme replacement therapy, gene therapy, and thymus implantation represent other forms of treatment in selected cases. The availability of newborn screening has greatly facilitated prompt recognition of SCID, which allows statistically significant improvement in survival after hematopoietic cell transplantation.
遗传性 T 细胞发育缺陷包括一组异质性疾病，其特征为外周 T 淋巴细胞减少，原因是 T 细胞前体细胞在胸腺内分化受损。这些疾病通常统称为严重联合免疫缺陷（SCID）。在某些情况下（渗漏性 SCID），缺陷基因的部分功能允许 T 细胞的部分发育。绝大多数 SCID 疾病是由于遗传缺陷导致造血干细胞的 T 细胞分化潜能受损，这些缺陷通过多种机制发生。然而，某些形式的 SCID 反映了胸腺基质细胞发育或功能受损。由于外周 T 细胞缺乏，导致生命早期就容易发生严重感染。除非进行免疫重建，最常见的方法是通过造血细胞移植，否则 SCID 必然致命。在某些情况下，酶替代疗法、基因疗法和胸腺移植代表了其他治疗形式。新生儿筛查的应用极大地促进了 SCID 的及时识别，这使得在进行造血细胞移植后，生存率得到了显著提高。
