重症联合免疫缺陷

对于所有 SCID 患者，HSCT 是唯一的确定性治疗方法。[3]Buckley RH. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Ann Rev Immunol. 2004:22:625-655.http://www.ncbi.nlm.nih.gov/pubmed/15032591?tool=bestpractice.com[40]Filipovich A. Hematopoietic cell transplantation for correction of primary immunodeficiencies. Bone Marrow Transplant. 2008:42(Suppl 1):S49-S52.http://www.ncbi.nlm.nih.gov/pubmed/18724301?tool=bestpractice.com

在感染发生前的早期诊断与治疗最为重要，可显著改善SCID婴幼儿的长期生存情况。[3]Buckley RH. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Ann Rev Immunol. 2004:22:625-655.http://www.ncbi.nlm.nih.gov/pubmed/15032591?tool=bestpractice.com[8]Fischer A. Severe combined immunodeficiencies (SCID). Clin Exp Immunol. 2000:122:143-149.http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11091267http://www.ncbi.nlm.nih.gov/pubmed/11091267?tool=bestpractice.com[42]Dvorak CC, Cowan MJ. Hematopoietic stem cell transplantation for primary immune deficiency disease. Bone Marrow Transplant. 2008;41:119-126.http://www.ncbi.nlm.nih.gov/pubmed/17968328?tool=bestpractice.com

早期（出生 3.5 个月内）进行 HSCT 可改善生存情况。[3]Buckley RH. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Ann Rev Immunol. 2004:22:625-655.http://www.ncbi.nlm.nih.gov/pubmed/15032591?tool=bestpractice.com[44]Pai SY, Logan BR, Griffith LM, et al. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med. 2014;371:434-446.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183064/http://www.ncbi.nlm.nih.gov/pubmed/25075835?tool=bestpractice.com使用人白细胞抗原 (HLA) 相合的同胞供体进行干细胞移植是首选方法，多项研究已经证实，与非亲缘 HLA 相合供体或亲缘 HLA 不相合供体移植相比，HLA 相合同胞供体干细胞移植的植活率更高，免疫重建及总生存情况更好。[42]Dvorak CC, Cowan MJ. Hematopoietic stem cell transplantation for primary immune deficiency disease. Bone Marrow Transplant. 2008;41:119-126.http://www.ncbi.nlm.nih.gov/pubmed/17968328?tool=bestpractice.com[45]Griffith LM, Cowan MJ, Kohn DB, et al. Allogeneic hematopoietic cell transplantation for primary immune deficiency diseases: current status and critical needs. J Allergy Clin Immunol. 2008:122:1087-1096.http://www.ncbi.nlm.nih.gov/pubmed/18992926?tool=bestpractice.com[46]Grunebaum E, Mazzolari E, Porta F, et al. Bone marrow transplantation for severe combined immune deficiency. JAMA. 2006:295:508-518.http://www.ncbi.nlm.nih.gov/pubmed/16449616?tool=bestpractice.com

不幸的是，SCID患者的HSCT治疗方案并不统一，并且还需要多中心合作研究来正规化治疗，并获得标准的最佳方法。[45]Griffith LM, Cowan MJ, Kohn DB, et al. Allogeneic hematopoietic cell transplantation for primary immune deficiency diseases: current status and critical needs. J Allergy Clin Immunol. 2008:122:1087-1096.http://www.ncbi.nlm.nih.gov/pubmed/18992926?tool=bestpractice.com[47]Griffith LM, Cowan MJ, Notarangelo LD, et al. Primary immune deficiency treatment consortium (PIDTC) report. J Allergy Clin Immunol. 2014;133:335-347.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960312/http://www.ncbi.nlm.nih.gov/pubmed/24139498?tool=bestpractice.com

在HSCT之前，应将已知患有SCID的婴幼儿与患病儿童及成人进行隔离，但不要求对其进行经验性住院治疗。

配方奶粉喂养应使用煮沸的过滤水。

患者母亲应就巨细胞病毒（CMV）进行测试，若血清测试结果为阳性，则不应采用母乳喂养。若需要应用血液或血液制品，则应对血液或血液制品进行照射处理，并保证血清CMV检测结果为阴性。

应避免使用任何活疫苗（包括轮状病毒疫苗）与卡介苗 (BCG)。[1]Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136:1186-1205.http://www.jacionline.org/article/S0091-6749(15)00883-0/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/26371839?tool=bestpractice.com[48]Bakare N, Menschik D, Tiernan R, et al. Severe combined immunodeficiency (SCID) and rotavirus vaccination: reports to the Vaccine Adverse Events Reporting System (VAERS). Vaccine. 2010;28:6609-6612.http://www.ncbi.nlm.nih.gov/pubmed/20674876?tool=bestpractice.com在那些常规进行BCG疫苗接种的国家中，应采用利福平和异烟肼进行预防性治疗。

在HSCT之前有进行替代性静脉注射免疫球蛋白（IVIG）治疗的指征，并可能在HSCT之后仍需要静脉注射免疫球蛋白来治疗持续性体液免疫缺陷。

推荐在移植前进行真菌、病毒与耶氏肺孢子虫感染的预防治疗。

仅可被用于腺苷脱氨酶缺陷型SCID患者中。

并非病因性治疗方法，而是可以进行HSCT或基因疗法前的一种暂缓治疗方法。

替代的酶以聚乙二醇(PEG)连接腺苷脱氨酶（PEG-ADA）形式起作用。已经证实，PEG-ADA 能够减少淋巴毒性代谢物（腺苷与脱氧腺苷），并恢复酶活性。[49]Chan B, Wara D, Bastian J, et al. Long-term efficacy of enzyme replacement therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID). Clin Immunol. 2005:117:133-143.http://www.ncbi.nlm.nih.gov/pubmed/16112907?tool=bestpractice.com

PEG-ADA的半衰期为3~6天，之后需要进行每周1次或2次用药，这可能会引起治疗依从性问题。

在一项回顾性研究中，40%治疗后的患者在开始PEG-ADA治疗后仍需补充免疫球蛋白治疗。仅接受 PEG-ADA 治疗患者的生存率为 85%。[49]Chan B, Wara D, Bastian J, et al. Long-term efficacy of enzyme replacement therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID). Clin Immunol. 2005:117:133-143.http://www.ncbi.nlm.nih.gov/pubmed/16112907?tool=bestpractice.com[50]Booth C, Hershfield M, Notarangelo L, et al. Management options for adenosine deaminase deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006). Clin Immunol. 2007;123:139-147.http://www.ncbi.nlm.nih.gov/pubmed/17300989?tool=bestpractice.com