Skip to main content

Advertisement

SpringerLink
Log in

Primary Immunodeficiency Disorders Among North Indian Children

  • Original Article
  • Published:
The Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Objectives

To report the distribution pattern of various categories of primary immunodeficiency disorders (PIDs) in children from North India, frequency of warning signs and critical parameters for evaluation.

Methods

In this retrospective study, 528 children below 18 y of age after clinical assessment and presentation suggestive of PID were further screened by immunophenotyping for immune cell markers by flow cytometry.

Results

A total of 120 (23%) children were diagnosed with PID with median age at diagnosis being 2.5 y in males and 3.5 y in females and an average delay in diagnosis from onset of symptoms being approximately 5 y. Chronic lower respiratory tract infections, gastrointestinal symptoms like persistent diarrhea and failure to thrive were amongst the most common warning signs in these patients. PIDs were classified according to the International Union of Immunological Societies’ (IUIS) criteria. The diagnosis of index study subjects included combined humoral and cellular immunodeficiency (29%), phagocytic defects (29%), followed by predominantly antibody deficiency (18%), innate immunity and dysregulation (17%) and other well-defined syndromes (7%). A family history of PID (23%), consanguineous marriage (8%) and previous sibling death (23%) were observed as major clinical predictors/clues for underlying PID. All children received prophylactic antibiotics and/or antifungals in addition to specific therapy for underlying immune deficiency.

Conclusions

The field of PIDs in India remains largely unexplored and we are faced with various challenges in the diagnosis of PIDs due to lack of awareness as well as absence of equipped immunological laboratory support. The authors propose a methodical step-wise laboratory diagnostic approach that can facilitate early diagnosis and timely intervention of these mis/underdiagnosed disorders.

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

References

  1. Bousfiha A, Jeddane L, Al-Herz W, et al. The 2015 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol. 2015;35:727–38.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Chandra RK, Ghai OP. Primary immunodeficiency states in Indian children. Indian J Med Res. 1976;64:68–75.

    CAS  PubMed  Google Scholar 

  3. Datta U, Kumar L, Mehta S, Walia BN, Sharma BK, Sehgal S. Primary immunodeficiency defects seen in PGI--one year study. J Assoc Physicians India. 1984;32:701–4.

  4. Verma S, Sharma PK, Sivanandan S, et al. Spectrum of primary immune deficiency at a tertiary care hospital. Indian J Pediatr. 2008;75:143–8.

    Article  PubMed  Google Scholar 

  5. Gupta S, Madkaikar M, Singh S, Sehgal S. Primary immunodeficiencies in India: a perspective. Ann N Y Acad Sci. 2012;1250:73–9.

    Article  CAS  PubMed  Google Scholar 

  6. Al-Saud BK, Al-Sum Z, Alassiri H, et al. Clinical, immunological, and molecular characterization of hyper-IgM syndrome due to CD40 deficiency in eleven patients. J Clin Immunol. 2013;33:1325–35.

    Article  CAS  PubMed  Google Scholar 

  7. Chopra YR, Yadav SP. Status of primary immunodeficiency disorders in India. Indian Pediatr. 2013;50:974.

    Article  PubMed  Google Scholar 

  8. Madkaikar M, Mishra A, Ghosh K. Diagnostic approach to primary immunodeficiency disorders. Indian Pediatr. 2013;50:579–86.

    Article  CAS  PubMed  Google Scholar 

  9. Mishra A, Gupta M, Dalvi A, Ghosh K, Madkaikar M. Rapid flow cytometric prenatal diagnosis of primary immunodeficiency (PID) disorders. J Clin Immunol. 2014;34:316–22.

    Article  CAS  PubMed  Google Scholar 

  10. Fleisher TA, Madkaikar M, Rosenzweig SD. Application of flow cytometry in the evaluation of primary immunodeficiencies. Indian J Pediatr. 2016;83:444–9.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Reda SM, El-Ghoneimy DH, Afifi HM. Clinical predictors of primary immunodeficiency diseases in children. Allergy Asthma Immunol Res. 2013;5:88–95.

    Article  PubMed  Google Scholar 

  12. Modell V, Knaus M, Modell F, Roifman C, Orange J, Notarangelo LD. Global overview of primary immunodeficiencies: a report from Jeffrey Modell centers worldwide focused on diagnosis, treatment, and discovery. Immunol Res. 2014;60:132–44.

    Article  CAS  PubMed  Google Scholar 

  13. Keerthikumar S, Raju R, Kandasamy K, et al. RAPID: resource of Asian primary immunodeficiency diseases. Nucleic Acids Res. 2009;37:D863–7.

    Article  CAS  PubMed  Google Scholar 

  14. Chinnabhandar V, Yadav SP, Kaul D, Verma IC, Sachdeva A. Primary immunodeficiency disorders in the developing world: data from a hospital-based registry in India. Pediatr Hematol Oncol. 2014;31:207–11.

    Article  PubMed  Google Scholar 

  15. Subbarayan A, Colarusso G, Hughes SM, et al. Clinical features that identify children with primary immunodeficiency diseases. Pediatrics. 2011;127:810–6.

    Article  PubMed  Google Scholar 

  16. Slatter MA, Gennery AR. Clinical immunology review series: an approach to the patient with recurrent infections in childhood. Clin Exp Immunol. 2008;152:389–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jindal AK, Pilania RK, Rawat A, Singh S. Primary immunodeficiency disorders in India—a situational review. Front Immunol. 2017;8:714.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Notarangelo LD, Duse M, Ugazio AG. Immunodeficiency with hyper-IgM (HIM). Immunodefic Rev. 1992;3:101–21.

    CAS  PubMed  Google Scholar 

  19. Korthäuer U, Graf D, Mages HW, et al. Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM. Nature. 1993;361:539–41.

    Article  PubMed  Google Scholar 

  20. Harris ES, Weyrich AS, Zimmerman GA. Lessons from rare maladies: leukocyte adhesion deficiency syndromes. Curr Opin Hematol. 2013;20:16–25.

  21. Kristufek D, Aspalter RM, Eibi MM, Wolf HM. Characterisation of novel Brutons tyrosine kinase gene mutations in central European patients with agammaglobulinemia. Mol Immunol. 2007;44:1639–43.

    Article  CAS  PubMed  Google Scholar 

  22. Valiaho J, Smith CI, Vihinen M. BTKbase: the mutation database for X-linked agammaglobulinemia. Hum Mutat. 2006;27:1209–17.

    Article  CAS  PubMed  Google Scholar 

  23. Chun JK, Lee TJ, Song JW, Linton JA, Kim DS. Analysis of clinical presentations of Bruton disease: a review of 20 years of accumulated data from pediatric patients at severance hospital. Yonsei Med J. 2008;49:28–36.

  24. Jolles S. The variable in common variable immunodeficiency: a disease of complex phenotypes. J Allergy Clin Immunol Pract. 2013;1:545–56.

  25. Notarangelo LD. Primary immunodeficiencies. J Allergy Clin Immunol. 2010;125:S182–94.

    Article  PubMed  Google Scholar 

  26. Mohammadinejad P, Aghamohammadi A, Abolhassani H, et al. Pediatric patients with common variable immunodeficiency: long-term follow-up. J Investig Allergol Clin Immunol. 2012;22:208–14.

    CAS  PubMed  Google Scholar 

  27. Ameratunga R, Brewerton M, Slade C, et al. Comparison of diagnostic criteria for common variable immunodeficiency disorder. Front Immunol. 2014;5:415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Usmani GN, Woda BA, Newburger PE. Advances in understanding the pathogenesis of HLH. Br J Haematol. 2013;161:609–22.

    Article  CAS  PubMed  Google Scholar 

  29. Buchbinder D, Nugent DJ, Fillipovich AH. Wiskott–Aldrich syndrome: diagnosis, current management, and emerging treatments. Appl Clin Genet. 2014;7:55–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank the study subjects, for providing samples and supporting this work; the participating clinical staff, for their dedication to this research; Ms. Poonam, Ms. Jyoti, Mr. Pankaj, Mr. Anoop (Department of Transplant Immunology and Immunotherapeutics, All India Institute of Medical Sciences), for their help in processing of samples.

Author information

Authors and Affiliations

  1. Department of Transplant Immunology & Immunogenetics, All India Institute of Medical Sciences, New Delhi, 110029, India

    Devika Gupta, Deepshi Thakral, Prabin Kumar, Rinkee Kumari, Supreet K. Mohanty, Sushmita Chakraborty & Dipendra K. Mitra

  2. Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India

    Sushil K. Kabra, Rakesh Lodha & Narendra Bagri

Authors
  1. Devika Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Deepshi Thakral
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Prabin Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sushil K. Kabra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rakesh Lodha
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rinkee Kumari
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Supreet K. Mohanty
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sushmita Chakraborty
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Narendra Bagri
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Dipendra K. Mitra
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DG and DT: Concepts, design, definition of intellectual content, literature search, experimental studies, data analysis, manuscript preparation, editing, and review; SKK: Concepts, design, definition of intellectual content, experimental studies, data analysis, manuscript preparation and review; RL: Concepts, definition of intellectual content, clinical studies, manuscript editing, and review; NB: Design, literature search, experimental studies, data acquisition and analysis and manuscript preparation and review; SKM: Concepts, definition of intellectual content, clinical and experimental studies, data analysis, manuscript preparation and review; PK and RK: Definition of intellectual content, clinical and experimental studies, data analysis, manuscript preparation; SC: Definition of intellectual content, clinical studies, manuscript preparation, editing, and review; DKM: Concepts, design, definition of intellectual content, manuscript preparation, editing and review. DKM is the guarantor for this paper.

Corresponding author

Correspondence to Dipendra K. Mitra.

Ethics declarations

Conflict of Interest

None.

Source of Funding

Institutional (AIIMS, New Delhi, India).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gupta, D., Thakral, D., Kumar, P. et al. Primary Immunodeficiency Disorders Among North Indian Children. Indian J Pediatr 86, 885–891 (2019). https://doi.org/10.1007/s12098-019-02971-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12098-019-02971-y

Keywords

Search

Navigation