X-linked recessive ectodermal dysplasia with immunodeficiency is a rare primary immunodeficiency caused by hypomorphic mutations of the IKBKG gene encoding the nuclear factor κB essential modulator (NEMO) protein. This condition displays enormous allelic, immunological, and clinical heterogeneity, and therapeutic decisions are difficult because NEMO operates in both hematopoietic and nonhematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is potentially life-saving, but the small number of case reports available suggests it has been reserved for only the most severe cases. Here, we report the health status before HSCT, transplantation outcome, and clinical follow-up for a series of 29 patients from unrelated kindreds from 11 countries. Between them, these patients carry 23 different hypomorphic IKBKG mutations. HSCT was performed from HLA-identical related donors (n = 7), HLA-matched unrelated donors (n = 12), HLA-mismatched unrelated donors (n = 8), and HLA-haploidentical related donors (n = 2). Engraftment was documented in 24 patients, and graft-versus-host disease in 13 patients. Up to 7 patients died 0.2 to 12 months after HSCT. The global survival rate after HSCT among NEMO-deficient children was 74% at a median follow-up after HSCT of 57 months (range, 4-108 months). Preexisting mycobacterial infection and colitis were associated with poor HSCT outcome. The underlying mutation does not appear to have any influence, as patients with the same mutation had different outcomes. Transplantation did not appear to cure colitis, possibly as a result of cell-intrinsic disorders of the epithelial barrier. Overall, HSCT can cure most clinical features of patients with a variety of IKBKG mutations.

具有免疫缺陷的X连锁隐性外胚层发育不良是一种罕见的原发性免疫缺陷，是由编码核因子κB必需调节剂（NEMO）蛋白的IKBKG基因的亚同型突变引起的。这种疾病表现出巨大的等位基因，免疫学和临床异质性，并且由于NEMO在造血和非造血细胞中均起作用，因此难以做出治疗决定。造血干细胞移植（HSCT）可能挽救生命，但现有的少数病例报告表明，它仅适用于最严重的病例。在这里，我们报告了来自11个国家的无亲属的29例患者的HSCT之前的健康状况，移植结局和临床随访情况。这些患者之间携带着23种不同的亚变态幼稚园突变。HSCT由HLA相同的相关供体（n = 7），HLA匹配的不相关供体（n = 12），HLA失配的不相关供体（n = 8）和HLA单倍体相关的供体（n = 2）进行。记录有24例患者发生移植，13例患者发生移植物抗宿主病。HSCT后0.2至12个月，多达7例患者死亡。NEMO缺陷儿童HSCT后的全球存活率为74％，HSCT后的中位随访时间为57个月（范围4-108个月）。先前存在的分枝杆菌感染和结肠炎与HSCT结果差有关。潜在的突变似乎没有任何影响，因为具有相同突变的患者的预后不同。移植似乎不能治愈结肠炎，可能是由于上皮屏障的细胞内在疾病引起的。全面的，IKBKG突变。