Advertisement

Journal of Clinical Immunology

, Volume 34, Issue 6, pp 633–641 | Cite as

Clinical and Molecular Features of 38 Children with Chronic Granulomatous Disease in Mainland China

  • Huan Xu
  • Wen Tian
  • Shu-Juan Li
  • Lu-Ying Zhang
  • Wei Liu
  • Yao Zhao
  • Zhi-Yong Zhang
  • Xue-Mei Tang
  • Mo Wang
  • Dao-Qi Wu
  • Ji-Sheng Shi
  • Yuan Ding
  • Xiao-Dong Zhao
  • Xi-Qiang Yang
  • Li-Ping Jiang
Original Research

Abstract

Purpose

Chronic granulomatous disease (CGD) is an inherited disorder, with phagocytes failing to produce antimicrobial superoxide due to deficient NADPH oxidase activity. Mutations in the gene encoding CYBB are responsible for the majority of the CGD cases. To date, there have been no reports on large samples of children with CGD in China. Therefore, in this study, we described the clinical and molecular features of 38 suspected CGD patients from 36 unrelated Chinese families.

Methods

Clinical diagnosis was performed using dihydrorhodamine assays detected by flow cytometry. Molecular analysis was used to identify underlying CGD-causative genes.

Results

The mean age of onset in our 38 patients was 3.4 months, while the mean age at diagnosis was 31.7 months. Apart from recurrent pneumonia and abscesses, tuberculosis (TB) and Bacille Calmette-Guerin (BCG) infections were notable features in our cohort. Overall, 17 cases died and patient 1 did not participate in the follow-up period . In total, we identified 29 different CYBB gene mutations in 31 patients. We found NCF1 and CYBA mutations in 3 and 2 patients, respectively. In addition, we identified 31 carriers and prenatally diagnosed 4 CGD and 4 healthy fetuses.

Conclusions

The results of our study demonstrate that children with BCG infections or recurrent TB infections should have immune function screening tests performed. Moreover, newborns with family histories of primary immunodeficiency diseases should avoid of BCG vaccination. Molecular analysis is an important tool for identifying patients, carriers, and high-risk CGD fetuses.

Keywords

Bacille Calmette-Guerin and mycobacterium tuberculosis infections children chronic granulomatous disease clinical features gene mutation prenatal diagnosis 

Notes

Acknowledgment

This study was supported by grants from Key Project of Chongqing Health Bureau (2012-1-048), the Scientific and technology Committee of Yuzhong District of Chongqing (20110313) and Public Welfare Scientific Research Project of China (201402012). We thank the patients and their family members for their cooperation.

Conflict of interest statement

There was no conflict of interest to declare.

References

  1. 1.
    Holland SM. Chronic granulomatous disease. Hematology/Oncology Clinics of North America. 2013;27:89–99.CrossRefPubMedGoogle Scholar
  2. 2.
    Holland SM. Chronic granulomatous disease. Clinical Reviews in Allergy and Immunology. 2010;38:3–10.CrossRefPubMedGoogle Scholar
  3. 3.
    Mahdaviani SA, Mohajerani SA, Rezaei N, et al. Pulmonary manifestations of chronic granulomatous disease. Expert Review of Clinical Immunology. 2013;9:153–60.CrossRefPubMedGoogle Scholar
  4. 4.
    Gardiner GJ, Deffit SN, McLetchie S, et al. A role for NADPH oxidase in antigen presentation. Frontiers in Immunology. 2013;4:295.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Segal BH, Leto TL, Gallin JI, et al. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore). 2000;79:170–200.CrossRefGoogle Scholar
  6. 6.
    Roos D, de Boer M. Molecular diagnosis of chronic granulomatous disease. Clinical and Experimental Immunology. 2014;175(2):139–49.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Köker MY, Camcıoğlu Y, van Leeuwen K, et al. Clinical, functional, and genetic characterization of chronic granulomatous disease in 89 Turkish patients. The Journal of Allergy and Clinical Immunology. 2013;132:1156–63.CrossRefPubMedGoogle Scholar
  8. 8.
    van den Berg JM, van Koppen E, et al. Chronic granulomatous disease: the European experience. PLoS One. 2009;4:e5234.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Lee PP, Chan KW, Jiang L, et al. Susceptibility to mycobacterial infections in children with X-linked chronic granulomatous disease: a review of 17 patients living in a region endemic for tuberculosis. Pediatric Infectious Disease Journal. 2008;27:224–30.CrossRefPubMedGoogle Scholar
  10. 10.
    Liese J, Kloos S, Jendrossek V, et al. Long-term follow-up and outcome of 39 patients with chronic granulomatous disease. Journal of Pediatrics. 2000;137:687–93.CrossRefPubMedGoogle Scholar
  11. 11.
    Martire B, Rondelli R, Soresina A, et al. Clinical features, long-term follow-up and outcome of a large cohort of patients with Chronic Granulomatous Disease: an Italian multicenter study. Clinical Immunology. 2008;126:155–64.CrossRefPubMedGoogle Scholar
  12. 12.
    Williams DA, Tao W, Yang F, et al. Dominant negative mutation of the hematopoietic- specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency. Blood. 2000;96:1646–54.PubMedGoogle Scholar
  13. 13.
    Kim HY, Kim HJ, Ki CS, et al. Rapid determination of chimerism status using dihydrorhodamine assay in a patient with X-linked chronic granulomatous disease following hematopoietic stem cell transplantation. Annals of Laboratory Medicine. 2013;33:288–92.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Vowells SJ, Sekhsaria S, Malech HL, et al. Flow cytometric analysis of the granulocyte respiratory burst: a comparison study of fluorescent probes. Journal of Immunological Methods. 1995;178:89–97.CrossRefPubMedGoogle Scholar
  15. 15.
    Sun J, Wang Y, Liu D, et al. Prenatal diagnosis of X-linked chronic granulomatous disease by percutaneous umbilical blood sampling. Scandinavian Journal of Immunology. 2012;76:512–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Yavuz Köker M, Metin A, Ozgür TT, et al. Prenatal diagnosis of chronic granulomatous disease in a male fetus. Iranian Journal of Allergy, Asthma, and Immunology. 2009;8:57–61.PubMedGoogle Scholar
  17. 17.
    Åhlin A, Fugeläng J, de Boer M, et al. Chronic granulomatous disease - haematopoietic stem cell transplantation versus conventional treatment. Acta Paediatrica. 2013;102:1087–94.PubMedGoogle Scholar
  18. 18.
    Hesseling AC, Rabie H, Marais BJ, et al. Bacille Calmette-Guérin vaccine-induced disease in HIV-infected and HIV-uninfected children. Clinical Infectious Diseases. 2006;42:548–58.CrossRefPubMedGoogle Scholar
  19. 19.
    Huard RC, Lazzarini LC, Butler WR. PCR-based method to differentiate the subspecies of the mycobacterium tuberculosis complex on the basis of genomic deletions. Journal of Clinical Microbiology. 2003;41:1637–50.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Fattahi F, Badalzadeh M, Sedighipour L, et al. Inheritance pattern and clinical aspects of 93 Iranian patients with chronic granulomatous disease. Journal of Clinical Immunology. 2011;31:792–801.CrossRefPubMedGoogle Scholar
  21. 21.
    Winkelstein JA, Marino MC, Johnston Jr RB, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000;79:155–69.CrossRefGoogle Scholar
  22. 22.
    Wolach B, Gavrieli R, de Boer M, et al. Chronic granulomatous disease in Israel: clinical, functional and molecular studies of 38 patients. Clinical Immunology. 2008;129:103–14.CrossRefPubMedGoogle Scholar
  23. 23.
    Shojaei H, Rahimi-Hajiabadi H, Heidarieh P, et al. Molecular microbiological investigation of post-vaccination bacille Calmette-Guérin infection in Iranian patients. The International Journal of Tuberculosis and Lung Disease. 2011;15:1497–503.CrossRefPubMedGoogle Scholar
  24. 24.
    Norouzi S, Aghamohammadi A, Mamishi S, et al. Bacillus calmette-guérin (BCG) complications associated with primary immunodeficiency diseases. Journal of Infection. 2012;64:543–54.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Dankner WM, Waecker NJ, Essey MA, et al. Mycobacterium bovis infections in San Diego: a clinicoepidemiologic study of 73 patients and a historical review of a forgotten pathogen. Medicine (Baltimore). 1993;72:11–37.CrossRefGoogle Scholar
  26. 26.
    Hanoglu D, Ozgür TT, Ayvaz D, et al. Chronic granulomatous disease presenting with hypogammaglobulinemia. Journal of Investigational Allergology and Clinical Immunology. 2011;21:310–2.PubMedGoogle Scholar
  27. 27.
    Patiroglu T, Gungor HE, Lazaroski S, et al. Chronic granulomatous disease with markedly elevated IgE levels mimicking hyperimmunoglobulin E syndrome. Acta Microbiologica et Immunologica Hungarica. 2013;60:155–62.CrossRefPubMedGoogle Scholar
  28. 28.
    Heyworth PG, Noack D, Cross AR. Identification of a novel NCF-1 (p47-phox) pseudogene not containing the signature GT deletion: significance for A47° chronic granulomatous disease carrier detection. Blood. 2002;100:1845–51.CrossRefPubMedGoogle Scholar
  29. 29.
    El Kares R, Barbouche MR, Elloumi-Zghal H, et al. Genetic and mutational heterogeneity of autosomal recessive chronic granulomatous disease in Tunisia. Journal of Human Genetics. 2006;51:887–95.CrossRefPubMedGoogle Scholar
  30. 30.
    Noack D, Heyworth PG, Kyono W, et al. A second case of somatic triple mosaicism in the CYBB gene causing chronic granulomatous disease. Human Genetics. 2001;109(2):234–8.CrossRefPubMedGoogle Scholar
  31. 31.
    de Boer M, Bakker E, Van Lierde S, et al. Somatic triple mosaicism in a carrier of X-linked chronic granulomatous disease. Blood. 1998;91(1):252–7.PubMedGoogle Scholar
  32. 32.
    Kang EM, Malech HL. Advances in treatment for chronic granulomatous disease. Immunologic Research. 2009;43:77–84.CrossRefPubMedGoogle Scholar
  33. 33.
    The International Chronic Granulomatous Disease Cooperative Study Group. A controlled trial of interferon-gamma to prevent infection in chronic granulomatous disease. New England Journal of Medicine. 1991;324:509–16.CrossRefGoogle Scholar
  34. 34.
    Güngör T, Teira P, Slatter M, et al. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study. Lancet. 2014;383(9915):436–48.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Huan Xu
    • 1
  • Wen Tian
    • 1
  • Shu-Juan Li
    • 1
  • Lu-Ying Zhang
    • 1
  • Wei Liu
    • 1
  • Yao Zhao
    • 2
  • Zhi-Yong Zhang
    • 3
  • Xue-Mei Tang
    • 3
  • Mo Wang
    • 3
  • Dao-Qi Wu
    • 3
  • Ji-Sheng Shi
    • 3
  • Yuan Ding
    • 3
  • Xiao-Dong Zhao
    • 2
  • Xi-Qiang Yang
    • 1
  • Li-Ping Jiang
    • 1
  1. 1.Clinical Immunology LaboratoryChildren’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and DisordersChongqingChina
  2. 2.Laboratory Biosafety-2Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and DisordersChongqingChina
  3. 3.Department of Immunology and NephrologyChildren’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and DisordersChongqingChina

Personalised recommendations