Advertisement

Primary Immunodeficiency Disorders Among North Indian Children

  • Devika Gupta
  • Deepshi Thakral
  • Prabin Kumar
  • Sushil K. Kabra
  • Rakesh Lodha
  • Rinkee Kumari
  • Supreet K. Mohanty
  • Sushmita Chakraborty
  • Narendra Bagri
  • Dipendra K. MitraEmail author
Original Article
  • 51 Downloads

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.

Keywords

Primary immunodeficiencies X-linked agammaglobulinemia Common variable immune deficiency Hyper IgM syndrome Severe combined immune deficiency Leukocyte adhesion deficiency DHR 

Notes

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.

Authors’ Contribution

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.

Compliance with Ethical Standards

Conflict of Interest

None.

Source of Funding

Institutional (AIIMS, New Delhi, India).

References

  1. 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.CrossRefGoogle Scholar
  2. 2.
    Chandra RK, Ghai OP. Primary immunodeficiency states in Indian children. Indian J Med Res. 1976;64:68–75.Google Scholar
  3. 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.Google Scholar
  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.CrossRefGoogle Scholar
  5. 5.
    Gupta S, Madkaikar M, Singh S, Sehgal S. Primary immunodeficiencies in India: a perspective. Ann N Y Acad Sci. 2012;1250:73–9.CrossRefGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. 7.
    Chopra YR, Yadav SP. Status of primary immunodeficiency disorders in India. Indian Pediatr. 2013;50:974.CrossRefGoogle Scholar
  8. 8.
    Madkaikar M, Mishra A, Ghosh K. Diagnostic approach to primary immunodeficiency disorders. Indian Pediatr. 2013;50:579–86.CrossRefGoogle Scholar
  9. 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.CrossRefGoogle Scholar
  10. 10.
    Fleisher TA, Madkaikar M, Rosenzweig SD. Application of flow cytometry in the evaluation of primary immunodeficiencies. Indian J Pediatr. 2016;83:444–9.CrossRefGoogle Scholar
  11. 11.
    Reda SM, El-Ghoneimy DH, Afifi HM. Clinical predictors of primary immunodeficiency diseases in children. Allergy Asthma Immunol Res. 2013;5:88–95.CrossRefGoogle Scholar
  12. 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.CrossRefGoogle Scholar
  13. 13.
    Keerthikumar S, Raju R, Kandasamy K, et al. RAPID: resource of Asian primary immunodeficiency diseases. Nucleic Acids Res. 2009;37:D863–7.CrossRefGoogle Scholar
  14. 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.CrossRefGoogle Scholar
  15. 15.
    Subbarayan A, Colarusso G, Hughes SM, et al. Clinical features that identify children with primary immunodeficiency diseases. Pediatrics. 2011;127:810–6.CrossRefGoogle Scholar
  16. 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.CrossRefGoogle Scholar
  17. 17.
    Jindal AK, Pilania RK, Rawat A, Singh S. Primary immunodeficiency disorders in India—a situational review. Front Immunol. 2017;8:714.CrossRefGoogle Scholar
  18. 18.
    Notarangelo LD, Duse M, Ugazio AG. Immunodeficiency with hyper-IgM (HIM). Immunodefic Rev. 1992;3:101–21.Google Scholar
  19. 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.CrossRefGoogle Scholar
  20. 20.
    Harris ES, Weyrich AS, Zimmerman GA. Lessons from rare maladies: leukocyte adhesion deficiency syndromes. Curr Opin Hematol. 2013;20:16–25.Google Scholar
  21. 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.CrossRefGoogle Scholar
  22. 22.
    Valiaho J, Smith CI, Vihinen M. BTKbase: the mutation database for X-linked agammaglobulinemia. Hum Mutat. 2006;27:1209–17.CrossRefGoogle Scholar
  23. 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.Google Scholar
  24. 24.
    Jolles S. The variable in common variable immunodeficiency: a disease of complex phenotypes. J Allergy Clin Immunol Pract. 2013;1:545–56.Google Scholar
  25. 25.
    Notarangelo LD. Primary immunodeficiencies. J Allergy Clin Immunol. 2010;125:S182–94.CrossRefGoogle Scholar
  26. 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.Google Scholar
  27. 27.
    Ameratunga R, Brewerton M, Slade C, et al. Comparison of diagnostic criteria for common variable immunodeficiency disorder. Front Immunol. 2014;5:415.CrossRefGoogle Scholar
  28. 28.
    Usmani GN, Woda BA, Newburger PE. Advances in understanding the pathogenesis of HLH. Br J Haematol. 2013;161:609–22.CrossRefGoogle Scholar
  29. 29.
    Buchbinder D, Nugent DJ, Fillipovich AH. Wiskott–Aldrich syndrome: diagnosis, current management, and emerging treatments. Appl Clin Genet. 2014;7:55–66.CrossRefGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2019

Authors and Affiliations

  • Devika Gupta
    • 1
  • Deepshi Thakral
    • 1
  • Prabin Kumar
    • 1
  • Sushil K. Kabra
    • 2
  • Rakesh Lodha
    • 2
  • Rinkee Kumari
    • 1
  • Supreet K. Mohanty
    • 1
  • Sushmita Chakraborty
    • 1
  • Narendra Bagri
    • 2
  • Dipendra K. Mitra
    • 1
    Email author
  1. 1.Department of Transplant Immunology & ImmunogeneticsAll India Institute of Medical SciencesNew DelhiIndia
  2. 2.Department of PediatricsAll India Institute of Medical SciencesNew DelhiIndia

Personalised recommendations