Please wait a minute...
J Zhejiang Univ (Med Sci)  2019, Vol. 48 Issue (4): 351-357    DOI: 10.3785/j.issn.1008-9292.2019.08.01
    
Advances in newborn screening and immune system reconstitution of severe combined immunodeficiency
HUANG Shumin(),ZHAO Zhengyan*()
Department of Internal Medicine, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China
Download: HTML( 54 )   PDF(913KB)
Export: BibTeX | EndNote (RIS)      

Abstract  

Severe combined immunodeficiency disease (SCID) is a group of rare congenital diseases characterized by severe deficiencies in T lymphocyte counts and/or function. The recurrent, persistent and severe infections are its clinical manifestations. Neonatal screening and immune system reconstruction would improve the prognosis of SCID children. Newborn screening programs based on T-cell receptor excision circles (TRECs) quantitative detection have been carried out in clinical practice, however, the methods still have some limitations. Other new methods such as mass spectrometry and T lymphocyte-specific biomarker assays are still under investigation. Hematopoietic stem cell transplantation and gene therapy are the two main methods for reconstructing immune function in SCID children. Through improving the success rate of transplantation and the long-term safety and stability of viral vectors, some achievements have been made by many centers already. However, large-scale prospective studies are needed for evaluation of the long-term efficacy. In this article, the recent progress in newborn screening and immune reconstitution of SCID is reviewed.



Key wordsSevere combined immunodeficiency/diagnosis      Severe combined immunodeficiency/therapy      Neonatal screening      Hematopoietic stem cell transplantation      Genetic therapy      Review     
Received: 20 December 2018      Published: 30 October 2019
CLC:  R725.9  
Corresponding Authors: ZHAO Zhengyan     E-mail: huangsm93@zju.edu.cn;zhaozy@zju.edu.cn
Cite this article:

HUANG Shumin,ZHAO Zhengyan. Advances in newborn screening and immune system reconstitution of severe combined immunodeficiency. J Zhejiang Univ (Med Sci), 2019, 48(4): 351-357.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2019.08.01     OR     http://www.zjujournals.com/med/Y2019/V48/I4/351


重症联合免疫缺陷病新生儿筛查及免疫系统重建研究进展

重症联合免疫缺陷病是一组罕见的先天性疾病,特征为T淋巴细胞数量和(或)功能严重缺陷,临床可表现为反复、持续、严重的感染。新生儿筛查及免疫系统重建是影响重症联合免疫缺陷病患儿临床预后的关键。基于外周血干血斑T细胞受体切除环定量检测技术的新生儿筛查项目已在临床开展,但存在一定的局限性,其他新的方法如串联质谱分析、T淋巴细胞特异性生物标志物测定等正处于研究阶段。造血干细胞移植和基因治疗是现阶段重建患儿免疫功能的主要方法。各中心致力于提高移植成功率及病毒载体长期安全性、稳定性的研究已取得一定成果,但远期疗效仍需更多大规模的前瞻性临床研究来评估。本文对重症联合免疫缺陷病新生儿筛查及免疫系统重建的研究进展作一综述。


关键词: 重症联合免疫缺陷/诊断,  重症联合免疫缺陷/治疗,  新生儿筛查,  造血干细胞移植,  基因治疗,  综述 
[1]   CIRILLO E , GIARDINO G , GALLO V et al. Severe combined immunodeficiency-an update[J]. Ann N Y Acad Sci, 2015, 1356:90- 106
doi: 10.1111/nyas.12849
[2]   PAI S Y , LOGAN B R , GRIFFITH L M et al. Transplantation outcomes for severe combined immuno-deficiency, 2000-2009[J]. N Engl J Med, 2014, 371 (5): 434- 446
doi: 10.1056/NEJMoa1401177
[3]   CHAN A , SCALCHUNES C , BOYLE M et al. Early vs. delayed diagnosis of severe combined immuno-deficiency:a family perspective survey[J]. Clin Immunol, 2011, 138 (1): 3- 8
[4]   KWAN A , PUCK J M . History and current status of newborn screening for severe combined immuno-deficiency[J]. Semin Perinatol, 2015, 39 (3): 194- 205
doi: 10.1053/j.semperi.2015.03.004
[5]   KALMAN L , LINDEGREN M L , KOBRYNSKI L et al. Mutations in genes required for T-cell development:IL7R, CD45, IL2RG, JAK3, RAG1, RAG2, ARTEMIS, and ADA and severe combined immunodeficiency:HuGE review[J]. Genet Med, 2004, 6 (1): 16- 26
doi: 10.1097/01.GIM.0000105752.80592.A3
[6]   ANTONIA K , ABRAHAM R S , ROBERT C et al. Newborn screening for severe combined immuno-deficiency in 11 screening programs in the United States[J]. JAMA, 2014, 312 (7): 729- 738
doi: 10.1001/jama.2014.9132
[7]   CHIEN Y H , CHIANG S C , CHANGK L et al. Incidence of severe combined immunodeficiency through newborn screening in a Chinese population[J]. J Formos Med Assoc, 2015, 114 (1): 12- 16
doi: 10.1016/j.jfma.2012.10.020
[8]   CHAN K , PUCK J M . Development of population-based newborn screening for severe combined immunodeficiency[J]. J Allergy Clin Immunol, 2005, 115 (2): 391- 398
[9]   文旻, 王晓川 . 重症联合免疫缺陷病新生儿T淋巴细胞受体切割环筛查概况[J]. 临床儿科杂志, 2017, 35 (1): 73- 77
WEN Min , WANG Xiaochuan . Overview of T-cell receptor excision circles in newborn screening with severe combined immunodeficiency disease[J]. Journal of Clinical Pediatrics, 2017, 35 (1): 73- 77
doi: 10.3969/j.issn.1000-3606.2017.01.019
[10]   VERBSKY J W , BAKER M W , GROSSMAN W J et al. Newborn screening for severe combined immunodeficiency; the Wisconsin experience (2008-2011)[J]. J Clin Immunol, 2012, 32 (1): 82- 88
doi: 10.1007/s10875-011-9609-4
[11]   VAN DER SPEK J , GROENWOLD R H , VAN DER BURG M et al. TREC based newborn screening for severe combined immunodeficiency disease:A systematic review[J]. J Clin Immunol, 2015, 35 (4): 416- 430
doi: 10.1007/s10875-015-0152-6
[12]   THAKAR M S , HINTERMEYER M K , GRIES M G et al. A practical approach to newborn screening for severe combined immunodeficiency using the T cell receptor excision circle assay[J]. Front Immunol, 2017, 8:1470
doi: 10.3389/fimmu.2017.01470
[13]   VAN DER SPEK J , GROENWOLD R H , VAN DER BURG M et al. TREC based newborn screening for severe combined immunodeficiency disease:A systematic review[J]. J Clin Immunol, 2015, 35 (4): 416- 430
doi: 10.1007/s10875-015-0152-6
[14]   AMATUNI G S , CURRIER R J , CHURCH J A et al. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California, 2010-2017[J]. Pediatrics, 2019, 143 (2): pii:e20182300
doi: 10.1542/peds.2018-2300
[15]   COMEAU A M , HALE J E , PAIS Y et al. Guidelines for implementation of population-based newborn screening for severe combined immuno-deficiency[J]. J Inherit Metab Dis, 2010, 33 (Suppl 2): S273- S281
[16]   VOGEL B H , BONAGURA V , WEINBERG G A et al. Newborn screening for SCID in New York State:experience from the first two years[J]. J Clin Immunol, 2014, 34 (3): 289- 303
doi: 10.1007/s10875-014-0006-7
[17]   AZZARI C , LA MARCA G , RESTI M . Neonatal screening for severe combined immunodeficiency caused by an adenosine deaminase defect:a reliable and inexpensive method using tandem mass spectrometry[J]. J Allergy Clin Immunol, 2011, 127 (6): 1394- 1399
doi: 10.1016/j.jaci.2011.03.040
[18]   JIMMERSON L C , BUSHMAN L R , RAY M L et al. A LC-MS/MS method for quantifying adenosine, guanosine and inosine nucleotides in human cells[J]. Pharm Res, 2016, 34 (1): 1- 11
[19]   COLLINS C J , CHANG I J , JUNG S et al. Rapid multiplexed proteomic screening for primary immunodeficiency disorders from dried blood spots[J]. Front Immunol, 2018, 9:2756
doi: 10.3389/fimmu.2018.02756
[20]   MCGHEE S A , STIEHM E R , COWAN M et al. Two-tiered universal newborn screening strategy for severe combined immunodeficiency[J]. Mol Genet Metab, 2005, 86 (4): 427- 430
doi: 10.1016/j.ymgme.2005.09.005
[21]   JANIK D K , LINDAU-SHEPARD B , COMEAUA M et al. A multiplex immunoassay using the Guthrie specimen to detect T-cell deficiencies including severe combined immunodeficiency disease[J]. Clin Chem, 2010, 56 (9): 1460- 1465
doi: 10.1373/clinchem.2010.144329
[22]   GATTI R A , MEUWISSEN H J , ALLENH D et al. Immunological reconstitution of sex-linked lymphopenic immunological deficiency[J]. Lancet, 1968, 2 (7583): 1366- 1369
[23]   PAI S Y , LOGAN B R , GRIFFITHL M et al. Transplantation outcomes for severe combined immunodeficiency, 2000-2009[J]. N Engl J Med, 2014, 371 (5): 434- 446
doi: 10.1056/NEJMoa1401177
[24]   HASSAN A , LEE P , MAGGINA P et al. Host natural killer immunity is a key indicator of permissiveness for donor cell engraftment in patients with severe combined immunodeficiency[J]. J Allergy Clin Immunol, 2014, 133 (6): 1660- 1666
doi: 10.1016/j.jaci.2014.02.042
[25]   HEIMALL J , PUCK J , BUCKLEY R et al. Current knowledge and priorities for future research in late effects after hematopoietic stem cell transplantation (hct) for severe combined immunodeficiency patients:a consensus statement from the second pediatric blood and marrow transplant consortium international conference on late effects after pediatric HCT[J]. Biol Blood Marrow Transplant, 2017, 23 (3): 379- 387
doi: 10.1016/j.bbmt.2016.12.619
[26]   MORIO T , ATSUTA Y , TOMIZAWA D et al. Outcome of unrelated umbilical cord blood transplantation in 88 patients with primary immuno-deficiency in Japan[J]. Br J Haematol, 2011, 154 (3): 363- 372
doi: 10.1111/j.1365-2141.2011.08735.x
[27]   DVORAK C C , LONG-BOYLE J , DARA J et al. Low exposure busulfan conditioning to achieve sufficient multilineage chimerism in patients with severe combined immunodeficiency[J]. Biol Blood Marrow Transplant, 2019, 25 (7): 1355- 1362
doi: 10.1016/j.bbmt.2019.03.008
[28]   ALLEWELT H , EL-KHORAZATY J , MENDIZABAL A et al. Late effects after umbilical cord blood transplantation in very young children after busulfan-based, myeloablative conditioning[J]. Biol Blood Marrow Transplant, 2016, 22 (9): 1627- 1635
doi: 10.1016/j.bbmt.2016.05.024
[29]   PICARD C , BOBBY GASPAR H , AL-HERZ W et al. International union of immunological societies:2017 primary immunodeficiency diseases committee report on inborn errors of immunity[J]. J Clin Immunol, 2018, 38 (1): 96- 128
doi: 10.1007/s10875-017-0464-9
[30]   安云飞, 赵晓东 . 原发性免疫缺陷病基因治疗[J]. 中国实用儿科杂志, 2017, 32 (7): 511- 515
AN Yunfei , ZHAO Xiaodong . Gene therapy for primary immunodeficiency disease[J]. Chinese Journal of Practical Pediatrics, 2017, 32 (7): 511- 515
[31]   H?NIG M , SCHULZ A , FRIEDRICH W . Hematopoietic stem cell transplantation for severe combined immunodeficiency[J]. Klin Padiatr, 2011, 223 (6): 320- 325
doi: 10.1055/s-0031-1287826
[32]   FERRUA F , AIUTI A . Twenty-five years of gene therapy for ada-scid:from bubble babies to an approved drug[J]. Hum Gene Ther, 2017, 28 (11): 972- 981
doi: 10.1089/hum.2017.175
[33]   POLETTI V , CHARRIER S , CORRE G et al. Preclinical development of a lentiviral vector for gene therapy of X-linked severe combined immuno-deficiency[J]. Mol Ther Methods Clin Dev, 2018, 9:257- 269
doi: 10.1016/j.omtm.2018.03.002
[34]   HACEIN-BEY-ABINA S , GARRIGUE A , WANGG P et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1[J]. J Clin Invest, 2008, 118 (9): 3132- 3142
doi: 10.1172/JCI35700
[35]   HACEIN-BEY-ABINA S , PAI S Y , GASPARH B et al. A modified γ-retrovirus vector for X-linked severe combined immunodeficiency[J]. N Engl J Med, 2014, 371 (15): 1407- 1417
doi: 10.1056/NEJMoa1404588
[36]   NALDINI L . Gene therapy returns to centre stage[J]. Nature, 2015, 526 (7573): 351- 360
doi: 10.1038/nature15818
[37]   ZHOU S , MODY D , DERAVIN S S et al. A self-inactivating lentiviral vector for SCID-X1 gene therapy that does not activate LMO2 expression in human T cells[J]. Blood, 2010, 116 (6): 900- 908
doi: 10.1182/blood-2009-10-250209
[38]   MAMCARZ E , ZHOU S , LOCKEY T et al. Lentiviral gene therapy combined with low-dose busulfan in infants with SCID-X1[J]. N Engl J Med, 2019, 380 (16): 1525- 1534
doi: 10.1056/NEJMoa1815408
[1] CHEN Guangjie,WANG Xiaohao,TANG Daxing. Progress on evaluation, diagnosis and management of disorders of sex development[J]. J Zhejiang Univ (Med Sci), 2019, 48(4): 358-366.
[2] WU Dingwen,LU Bin,YANG Jianbin,YANG Rulai,HUANG Xinwen,TONG Fan,ZHENG Jing,ZHAO Zhengyan. Genetic analysis of newborns with abnormal metabolism of 3-hydroxyisovalerylcarnitine[J]. J Zhejiang Univ (Med Sci), 2019, 48(4): 390-396.
[3] TONG Fan,YANG Rulai,LIU Chang,WU Dingwen,ZHANG Ting,HUANG Xinwen,HONG Fang,QIAN Guling,HUANG Xiaolei,ZHOU Xuelian,SHU Qiang,ZHAO Zhengyan. Screening for hereditary tyrosinemia and genotype analysis in newborns[J]. J Zhejiang Univ (Med Sci), 2019, 48(4): 459-464.
[4] ZHU Ziling, TAN Jing, DENG Hong. Nucleus translocation of membrane/cytoplasm proteins in tumor cells[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 318-325.
[5] ZHANG Jianmin. Advances in surgical treatment of ischemic cerebrovascular disease[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 233-240.
[6] WU Yuxing, ZHANG Shihong, CHEN Zhong. The roles of habenula and related neural circuits in neuropsychiatric diseases[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 310-317.
[7] ZHANG Yunzhu, ZHU Chunpeng, LU Xinliang. Advances in serum biomarkers for early diagnosis of gastric cancer[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 326-333.
[8] WU Binbin,YANG Yi. Biomarkers of cardiac surgery-associated acute kidney injury: a narrative review[J]. J Zhejiang Univ (Med Sci), 2019, 48(2): 224-229.
[9] YANG Kun,HU Xiaosheng. Research progress on miR-21 in heart diseases[J]. J Zhejiang Univ (Med Sci), 2019, 48(2): 214-218.
[10] XU Li,XU Ming,TONG Xiangmin. Effects of aerobic glycolysis on pathogenesis and drug resistance of non-Hodgkin lymphoma[J]. J Zhejiang Univ (Med Sci), 2019, 48(2): 219-223.
[11] Baboo Kalianee Devi,CHEN Zhengyun,ZHANG Xinmei. Progress on medical treatment in the management of adenomyosis[J]. J Zhejiang Univ (Med Sci), 2019, 48(2): 142-147.
[12] SONG Fangjun,GUO Hongtao. Progress on structural biology of voltage-gated ion channels[J]. J Zhejiang Univ (Med Sci), 2019, 48(1): 25-33.
[13] ZHAO Shihao,ZHANG Xue,KE Yuehai. Progress on correlation between cell senescence and idiopathic pulmonary fibrosis[J]. J Zhejiang Univ (Med Sci), 2019, 48(1): 111-115.
[14] HONG Feifan,LI Yuezhou. Application of mechanosensitive channels in sonogenetics[J]. J Zhejiang Univ (Med Sci), 2019, 48(1): 34-38.
[15] XIAO Li,TONG Xiaoyong. Advances in molecular mechanism of vascular remodeling in pulmonary arterial hypertension[J]. J Zhejiang Univ (Med Sci), 2019, 48(1): 102-110.