X连锁重症联合免疫缺陷病的根治治疗进展
收稿日期: 2023-11-21
网络出版日期: 2024-07-08
Progress in radical treatment of X-linked severe combined immunodeficiency
Received date: 2023-11-21
Online published: 2024-07-08
X连锁重症联合免疫缺陷病（X-SCID）是重症联合免疫缺陷病中最常见的类型，典型的免疫学特征是成熟T细胞和NK细胞完全缺失而B细胞数量正常或升高。临床特征是从婴儿早期即出现复发和严重的机会性感染。该病患者往往起病早，临床表现重，预后差，如果没有得到及时的诊断和治疗，大多在2岁以内死亡。造血干细胞移植（haematopoietic stem cell transplantation，HSCT）是首选的治疗方法，如果采用HLA 匹配的同胞供体，生存率极高（>90%）。然而，当使用替代供体时，成功率和存活率往往较低。因此基因治疗已被开发为替代疗法。
关键词： X连锁重症联合免疫缺陷; 造血干细胞移植; 基因治疗; 基因编辑
柴星苑 , 张志勇 综述 , 赵晓东 审校 . X连锁重症联合免疫缺陷病的根治治疗进展[J]. 临床儿科杂志, 2024 , 42(7) : 659 -662 . DOI: 10.12372/jcp.2024.23e1107
X-linked severe combined immunodeficiency (X-SCID) is the most common type of severe combined immunodeficiency disease. The typical immunological feature is the complete absence of mature T cells and NK cells with normal or elevated B cell numbers. The clinical features are recurrent and severe opportunistic infections from early infancy. The patients often have early onset, severe clinical manifestations and poor prognosis. Without prompt diagnosis and treatment, most patients die within the age of two. Hematopoietic stem cell transplantation is the preferred treatment and has a very high survival rate (>90 %) if HLA-matched sibling donors are used. However, when alternative donors are used, the success rate and survival rate are often lower. Gene therapy has been developed as an alternative therapy.
| [1] | Tangye SG, Al-Herz W, Bousfiha A, et al. Correction to: human inborn errors of immunity: 2019 update on the classification from the international union of immunological societies expert committee[J]. J Clin Immunol, 2020, 40(1): 24-64. |
| [2] | Kumrah R, Vignesh P, Patra P, et al. Genetics of severe combined immunodeficiency[J]. Genes Dis, 2019, 7(1): 52-61. |
| [3] | Hernandez JD, Hsieh EWY. A great disturbance in the force: IL-2 receptor defects disrupt immune homeostasis[J]. Curr Opin Pediatr, 2022, 34(6): 580-588. |
| [4] | Lim CK, Abolhassani H, Appelberg SK, et al. IL2RG hypomorphic mutation: identification of a novel pathogenic mutation in exon 8 and a review of the literature[J]. Allergy Asthma Clin Immunol, 2019, 15: 2. |
| [5] | Bustamante Ogando JC, Partida Gaytán A, Aldave Becerra JC, et al. Latin American consensus on the supportive management of patients with severe combined immunodeficiency[J]. J Allergy Clin Immunol, 2019, 144(4): 897-905. |
| [6] | Gatti RA, Meuwissen HJ, Allen HD, et al. Immunological reconstitution of sex-linked lymphopenic immunological deficiency[J]. Lancet, 1968, 2(7583): 1366-1369. |
| [7] | Miyamoto S, Umeda K, Kurata M, et al. Hematopoietic cell transplantation for inborn errors of immunity other than severe combined immunodeficiency in Japan: retrospective analysis for 1985-2016[J]. J Clin Immunol, 2022, 42(3): 529-545. |
| [8] | Lankester AC, Albert MH, Booth C, et al. EBMT/ESID inborn errors working party guidelines for hematopoietic stem cell transplantation for inborn errors of immunity[J]. Bone Marrow Transplant, 2021, 56(9): 2052-2062. |
| [9] | Pai SY, Logan BR, Griffith LM, et al. Transplantation outcomes for severe combined immunodeficiency, 2000-2009[J]. N Engl J Med, 2014, 371(5): 434-446. |
| [10] | Ozturk E, Catak MC, Kiykim A, et al. Correction to: clinical and laboratory factors affecting the prognosis of severe combined immunodeficiency[J]. J Clin Immunol, 2023, 43(5): 1036-1050. |
| [11] | Gennery AR. The challenges presented by haematopoietic stem cell transplantation in children with primary immunodeficiency[J]. Br Med Bull, 2020, 135(1): 4-15. |
| [12] | Manor U, Lev A, Simon AJ, et al. Immune reconstitution after HSCT in SCID-a cohort of conditioned and unconditioned patients[J]. Immunol Res, 2019, 67(2-3):166-175. |
| [13] | Miggelbrink AM, Logan BR, Buckley RH, et al. B-cell differentiation and IL-21 response in IL2RG/JAK3 SCID patients after hematopoietic stem cell transplantation[J]. Blood, 2018, 131(26): 2967-2977. |
| [14] | Tsilifis C, Lum SH, Nademi Z, et al. TCRαβ-depleted haploidentical grafts are a safe alternative to HLA-matched unrelated donor stem cell transplants for infants with severe combined immunodeficiency[J]. J Clin Immunol, 2022, 42(4): 851-858. |
| [15] | Hacein-Bey-Abina S, Pai SY, Gaspar HB, et al. A modified γ-retrovirus vector for X-linked severe combined immunodeficiency[J]. N Engl J Med, 2014, 371(15): 1407-1417. |
| [16] | Pai SY, Thrasher AJ. Gene therapy for X-linked severe combined immunodeficiency: historical outcomes and current status[J]. J Allergy Clin Immunol, 2020, 146(2): 258-261. |
| [17] | Booth C, Kohn DB, Armant M, et al. Lentiviral gene therapy with low dose conditioning for X-linked SCID results in complete immune reconstitution and no evidence of clonal expansion[J]. Blood, 2022, 140: 7770-7771. |
| [18] | Sung-Yun Pai CB, Kohn DB, Armant MA, et al. Universal survival and superior immune reconstitution after lentiviral gene therapy with low dose conditioning for X-linked SCID (SCID-X1)[J]. Mol Ther, 2023, 31: 1-8. |
| [19] | Touzot F, Moshous D, Creidy R, et al. Faster T-cell development following gene therapy compared with haploidentical HSCT in the treatment of SCID-X1[J]. Blood, 2015, 125(23): 3563-3569. |
| [20] | Liu X, Li G, Liu Y, et al. Advances in CRISPR/Cas gene therapy for inborn errors of immunity[J]. Front Immunol, 2023, 14: 1111777. |
| [21] | Brault J, Liu T, Liu S, et al. CRISPR-Cas9-AAV versus lentivector transduction for genome modification of X-linked severe combined immunodeficiency hematopoietic stem cells[J]. Front Immunol, 2023, 13: 1067417. |
| [22] | Jang Y, Kim YS, Wielgosz MM, et al. Optimizing lentiviral vector transduction of hematopoietic stem cells for gene therapy[J]. Gene Ther, 2020, 27(12): 545-556. |
| [23] | Bauler M, Roberts JK, Wu CC, et al. Production of lentiviral vectors using suspension cells grown in serum-free media[J]. Mol Ther Methods Clin Dev, 2019, 17: 58-68. |
| [24] | Bernadin O, Amirache F, Girard-Gagnepain A, et al. Baboon envelope LVs efficiently transduced human adult, fetal, and progenitor T cells and corrected SCID-X1 T-cell deficiency[J]. Blood Adv, 2019, 3(3): 461-475. |
/
| 〈 |
|
〉 |
沪公网安备 31011002000392号
