Skip to main content

Advertisement

SpringerLink
Log in

Clinical Characteristics and Genetic Profiles of 44 Patients with Severe Combined Immunodeficiency (SCID): Report from Shanghai, China (2004–2011)

  • Original Research
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Severe combined immunodeficiency (SCID), a rare type of genetic associated immune disorder, is poorly characterized in mainland China. We retrospectively reviewed 44 patients with SCID who received treatment from 2004 to 2011 in Shanghai, China, and herein summarize their clinical manifestations and immunological and preliminary genetic features. The male-to-female ratio was 10:1. Twenty five patients presented with X-SCID symptoms. Only one patient was diagnosed before the onset of symptoms due to positive family history. The mean time of delay in the diagnosis of X-SCID was 2.69 months (range, 0.5–8.67). Thirty-seven of the 44 patients died by the end of 2011 with the mean age of death being 7.87 months (range, 1.33–31). Six patients received hematopoietic stem cell transplantation (HSCT); only one of them survived, who was transplanted twice. The time between onset and death was shorter in the HSCT-treated group compared with the untreated group (2.87 ± 1.28 and 3.34 ± 0.59 months, respectively), probably due to active infections during transplantation. Bacillus Calmette–Guérin (BCG) complications occurred in 14 of the 34 patients who received BCG vaccination. Transfusion-induced graft-versus-host disease occurred in 5 patients. Total 20 mutations in interleukin-2 receptor subunit gamma (IL2RG) were identified in 22 patients, including 11 novel mutations. Most patients were misdiagnosed before referred to our SCID Center. Therefore, establishing more diagnostic centers dedicated to the care of PID and accessible by primary immunodeficiency patients will facilitate early, correct diagnosis and better care of SCID in China.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

ADA:

Adenosine deaminase

ALC:

Absolute lymphocyte count

BCG:

Bacillus Calmette–Guérin

GVHD:

Graft-versus-host disease

HLA:

Human leukocyte antigen

HSCT:

Hematopoietic stem cell transplantation

IL2RG :

Interleukin-2 receptor subunit gamma

NK:

Natural killer

PID:

Primary immunodeficiency disease

SCID:

Severe combined immunodeficiency

References

  1. Fischer A, Le DF, Hacein-Bey-Abina S, et al. Severe combined immunodeficiency. A model disease for molecular immunology and therapy. Immunol Rev. 2005;203:98–109.

    Article  PubMed  CAS  Google Scholar 

  2. Cossu F. Genetics of SCID. Ital J Pediatr. 2010;36:76.

    Article  PubMed  Google Scholar 

  3. Kalman L, Lindegren ML, 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. Genet Med. 2004;6(1):16–26.

    Article  PubMed  CAS  Google Scholar 

  4. Jones AM, Clark PA, Katz F, et al. B-cell-negative severe combined immunodeficiency associated with a common gamma chain mutation. Hum Genet. 1997;99(5):677–80.

    Article  PubMed  CAS  Google Scholar 

  5. DiSanto JP, Rieux-Laucat F, Dautry-Varsat A, Fischer A, de Saint Basile G. Defective human interleukin 2 receptor gamma chain in an atypical X chromosome-linked severe combined immunodeficiency with peripheral T cells. Proc Natl Acad Sci U S A. 1994;91(20):9466–70.

    Article  PubMed  CAS  Google Scholar 

  6. Schmalstieg FC, Leonard WJ, Noguchi M, et al. Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency. J Clin Invest. 1995;95(3):1169–73.

    Article  PubMed  CAS  Google Scholar 

  7. Ginn SL, Smyth C, Wong M, Bennetts B, Rowe PB, Alexander IE. A novel splice-site mutation in the common gamma chain (gammac) gene IL2RG results in X-linked severe combined immunodeficiency with an atypical NK+ phenotype. Hum Mutat. 2004;23(5):522–3.

    Article  PubMed  Google Scholar 

  8. Kobayashi S, Murayama S, Tatsuzawa O, et al. X-linked severe combined immunodeficiency (X-SCID) with high blood levels of immunoglobulins and Aspergillus pneumonia successfully treated with micafangin followed by unrelated cord blood stem cell transplantation. Eur J Pediatr. 2007;166(3):207–10.

    Article  PubMed  Google Scholar 

  9. Gennery AR, Slatter MA, Grandin L, et al. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better. J Allergy Clin Immunol. 2010;126(3):602-10.e1–11.

    Article  Google Scholar 

  10. Stephan JL, Vlekova V, Le DF, et al. Severe combined immunodeficiency: a retrospective single-center study of clinical presentation and outcome in 117 patients. J Pediatr. 1993;123(4):564–72.

    Article  PubMed  CAS  Google Scholar 

  11. Lee PP, Chan KW, Chen TX, et al. Molecular diagnosis of severe combined immunodeficiency–identification of IL2RG, JAK3, IL7R, DCLRE1C, RAG1, and RAG2 mutations in a cohort of Chinese and Southeast Asian children. J Clin Immunol. 2011;31(2):281–96.

    Article  PubMed  CAS  Google Scholar 

  12. Tsuji Y, Imai K, Kajiwara M, et al. Hematopoietic stem cell transplantation for 30 patients with primary immunodeficiency diseases: 20 years experience of a single team. Bone Marrow Transplant. 2006;37(5):469–77.

    Article  PubMed  CAS  Google Scholar 

  13. Wang LL, Jin YY, Hao YQ, et al. Distribution and clinical features of primary immunodeficiency diseases in Chinese children (2004–2009). J Clin Immunol. 2011;31(3):297–308.

    Article  PubMed  Google Scholar 

  14. Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. 1999;93(3):190–7.

    Article  PubMed  CAS  Google Scholar 

  15. Comans-Bitter WM, de Groot R, van den Beemd R, et al. Immunophenotyping of blood lymphocytes in childhood. Reference values for lymphocyte subpopulations. J Pediatr. 1997;130(3):388–93.

    Article  PubMed  CAS  Google Scholar 

  16. Muller SM, Ege M, Pottharst A, Schulz AS, Schwarz K, Friedrich W. Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients. Blood. 2001;98(6):1847–51.

    Article  PubMed  CAS  Google Scholar 

  17. Buckley RH, Schiff RI, Schiff SE, et al. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr. 1997;130(3):378–87.

    Article  PubMed  CAS  Google Scholar 

  18. Hague RA, Rassam S, Morgan G, Cant AJ. Early diagnosis of severe combined immunodeficiency syndrome. Arch Dis Child. 1994;70(4):260–3.

    Article  PubMed  CAS  Google Scholar 

  19. Reda SM, Afifi HM, Amine MM. Primary immunodeficiency diseases in Egyptian children: a single-center study. J Clin Immunol. 2009;29(3):343–51.

    Article  PubMed  Google Scholar 

  20. Lau YL, Jones BM, Yeung CY. Biphasic rise of serum immunoglobulins G and A and sex influence on serum immunoglobulin M in normal Chinese children. J Paediatr Child Health. 1992;28(3):240–3.

    Article  PubMed  CAS  Google Scholar 

  21. Puck JM, Pepper AE, Henthorn PS, et al. Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency. Blood. 1997;89(6):1968–77.

    PubMed  CAS  Google Scholar 

  22. Lipstein EA, Vorono S, Browning MF, et al. Systematic evidence review of newborn screening and treatment of severe combined immunodeficiency. Pediatrics. 2010;125(5):e1226–35.

    Article  PubMed  Google Scholar 

  23. Zhao HJ, Chen TX, Hao YQ, Zhou YF, Ying DM. Overview of clinical occurrence of primary immunodeficiency disorders in children. Zhonghua Er Ke Za Zhi. 2006;44(6):403–6.

    PubMed  Google Scholar 

  24. Felgentreff K, Perez-Becker R, Speckmann C, et al. Clinical and immunological manifestations of patients with atypical severe combined immunodeficiency. Clin Immunol. 2011;141(1):73–82.

    PubMed  CAS  Google Scholar 

  25. Giliani S, Mori L, de Saint Basile G, et al. Interleukin-7 receptor alpha (IL-7Ralpha) deficiency: cellular and molecular bases. Analysis of clinical, immunological, and molecular features in 16 novel patients. Immunol Rev. 2005;203:110–26.

    Article  PubMed  CAS  Google Scholar 

  26. Arredondo-Vega FX, Santisteban I, Daniels S, Toutain S, Hershfield MS. Adenosine deaminase deficiency: genotype-phenotype correlations based on expressed activity of 29 mutant alleles. Am J Hum Genet. 1998;63(4):1049–59.

    Article  PubMed  CAS  Google Scholar 

  27. Gossage DL, Buckley RH. Prevalence of lymphocytopenia in severe combined immunodeficiency. N Engl J Med. 1990;323(20):1422–3.

    Article  PubMed  CAS  Google Scholar 

  28. Fugmann SD, Muller S, Friedrich W, Bartram CR, Schwarz K. Mutations in the gene for the common gamma chain (gammac) in X-linked severe combined immunodeficiency. Hum Genet. 1998;103(6):730–1.

    PubMed  CAS  Google Scholar 

  29. Lee PP, Chen TX, Jiang LP, et al. Clinical characteristics and genotype-phenotype correlation in 62 patients with X-linked agammaglobulinemia. J Clin Immunol. 2010;30(1):121–31.

    Article  PubMed  CAS  Google Scholar 

  30. Jin Y, Mazza C, Christie JR, et al. Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation. Blood. 2004;104(13):4010–9.

    Article  PubMed  CAS  Google Scholar 

  31. Conley ME, Howard V. Clinical findings leading to the diagnosis of X-linked agammaglobulinemia. J Pediatr. 2002;141(4):566–71.

    Article  PubMed  Google Scholar 

  32. Buckley RH. Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes. Immunol Res. 2011;49(1–3):25–43.

    Article  PubMed  Google Scholar 

  33. Petrovic A, Dorsey M, Miotke J, Shepherd C, Day N. Hematopoietic stem cell transplantation for pediatric patients with primary immunodeficiency diseases at All Children’s Hospital/University of South Florida. Immunol Res. 2009;44(1–3):169–78.

    Article  PubMed  CAS  Google Scholar 

  34. Chase NM, Verbsky JW, Routes JM. Newborn screening for T-cell deficiency. Curr Opin Allergy Clin Immunol. 2010;10(6):521–5.

    Article  PubMed  Google Scholar 

  35. O’Marcaigh AS, DeSantes K, Hu D, et al. Bone marrow transplantation for T-B- severe combined immunodeficiency disease in Athabascan-speaking native Americans. Bone Marrow Transplant. 2001;27(7):703–9.

    Article  PubMed  Google Scholar 

  36. Smogorzewska EM, Brooks J, Annett G, et al. T cell depleted haploidentical bone marrow transplantation for the treatment of children with severe combined immunodeficiency. Arch Immunol Ther Exp (Warsz). 2000;48(2):111–8.

    CAS  Google Scholar 

Download references

Statement of Financial Support

This research was supported by grants from National Natural Science Foundation of China (81273314) and Ph.D. Programs, Foundation of Shanghai Jiao Tong University School of Medicine (BXJ201025)

Author information

Authors and Affiliations

  1. Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 20092, China

    Chun-Mei Yao, Rui-Ming Cao, Xi Wang & Quan-Hua Liu

  2. Department of Immunology, Institute of Pediatric Translational Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Pudong New District, Shanghai, 200127, China

    Chun-Mei Yao, Hui Zhang, Ying-Ying Jin & Tong-Xin Chen

  3. Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, 110004, China

    Xiao-Hua Han

  4. Department of Internal Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130021, China

    Yi-Dan Zhang

  5. Division of Allergy and Immunology, Department of Pediatrics, Virginia Commonwealth University, Richmond, VA, 23298, USA

    Wei Zhao

Authors
  1. Chun-Mei Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-Hua Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yi-Dan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ying-Ying Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rui-Ming Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Quan-Hua Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tong-Xin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tong-Xin Chen.

Additional information

Chun-Mei Yao, Xiao-Hua Han and Yi-Dan Zhang are co-first authors and had equal contributions to the study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yao, CM., Han, XH., Zhang, YD. et al. Clinical Characteristics and Genetic Profiles of 44 Patients with Severe Combined Immunodeficiency (SCID): Report from Shanghai, China (2004–2011). J Clin Immunol 33, 526–539 (2013). https://doi.org/10.1007/s10875-012-9854-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-012-9854-1

Keywords

Search

Navigation