Yu Grace P, Nadeau Kari C, Berk David R, de Saint Basile Geneviève, Lambert Nathalie, Knapnougel Perrine, Roberts Joseph, Kavanau Kristina, Dunn Elizabeth, Stiehm E Richard, Lewis David B, Umetsu Dale T, Puck Jennifer M, Cowan Morton J
Division of Immunology and Allergy, Department of Pediatrics, Stanford University School of Medicine and Lucile Packard Children's Hospital at Stanford, Palo Alto, CA, USA.
Pediatr Transplant. 2011 Nov;15(7):733-41. doi: 10.1111/j.1399-3046.2011.01563.x. Epub 2011 Aug 23.
There are few reports of clinical presentation, genotype, and HCT outcomes for patients with T-B+NK+ SCID. Between 1981 and 2007, eight of 84 patients with SCID who received and/or were followed after HCT at UCSF had the T-B+NK+ phenotype. One additional patient with T-B+NK+ SCID was identified as the sibling of a patient treated at UCSF. Chart reviews were performed. Molecular analyses of IL7R, IL2RG, JAK3, and the genes encoding the CD3 T-cell receptor components δ (CD3D), ε (CD3E), and ζ (CD3Z) were carried out. IL7R mutations were documented in four patients and CD3D mutations in two others. Three patients had no defects found. Only two of nine patients had an HLA-matched related HCT donor. Both survived, and neither developed GVHD. Five of seven recipients of haploidentical grafts survived. Although the majority of reported cases of T-B+NK+ SCID are caused by defects in IL7R, CD3 complex defects were also found in this series and should be considered when evaluating patients with T-B+NK+ SCID. Additional genes, mutations in which account for T-B+NK+ SCID, remain to be found. Better approaches to early diagnosis and HCT treatment are needed for patients lacking an HLA-matched related donor.
关于T-B+NK+重症联合免疫缺陷（SCID）患者的临床表现、基因型和造血干细胞移植（HCT）结果的报道较少。1981年至2007年间，在加州大学旧金山分校接受HCT并/或在HCT后接受随访的84例SCID患者中，有8例具有T-B+NK+表型。另外一名T-B+NK+ SCID患者被确定为在加州大学旧金山分校接受治疗的一名患者的同胞。进行了病历审查。对IL7R、IL2RG、JAK3以及编码CD3 T细胞受体成分δ（CD3D）、ε（CD3E）和ζ（CD3Z）的基因进行了分子分析。4例患者记录有IL7R突变，另外2例有CD3D突变。3例患者未发现缺陷。9例患者中只有2例有HLA匹配的相关HCT供体。两人均存活，且均未发生移植物抗宿主病（GVHD）。7例单倍体移植受者中有5例存活。虽然大多数报道的T-B+NK+ SCID病例是由IL7R缺陷引起的，但本系列中也发现了CD3复合体缺陷，在评估T-B+NK+ SCID患者时应予以考虑。其他导致T-B+NK+ SCID的基因突变仍有待发现。对于缺乏HLA匹配相关供体的患者，需要更好的早期诊断和HCT治疗方法。
