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Diagnostic approach to primary immunodeficiency disorders

Indian Pediatrics volume 50, pages 579–586 (2013)Cite this article

Abstract

Primary immunodeficiency disorders (PIDs) are a heterogeneous group of inherited disorders that affect different components of the immune system. There are more than 150 different disorders which have been described till date. Despite major advances in the molecular characterization of PIDs over the last 20 years, many patients remain undiagnosed or are diagnosed too late with severe consequences. Recognizing different clinical manifestations of PID is the first most important step. It should be followed by use of appropriate diagnostic tools from a vast number of investigations available. This review will focus on important presenting features of PID and laboratory approach for diagnosis of suspected cases of PID.

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References

  1. Al-Herz W, Bousfiha A, Casanova JL, Chapel H, Conley ME, Cunningham-Rundles C, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. Frontiers in Immunology. 2011;2:54.

    PubMed  Article  Google Scholar 

  2. Piguet D, Tosi C, Luthi JM, Andresen I, Juge O. Redimune ((R)) NF Liquid, a ready-to-use, high-concentration intravenous immunoglobulin therapy preparation, is safe and typically well tolerated in the routine clinical management of a broad range of conditions. Clin Exp Immunol. 2008;152:45–49.

    PubMed  Article  CAS  Google Scholar 

  3. Notarangelo LD, Forino C, Mazzolari E. Stem cell transplantation in primary immunodeficiencies. Curr Opin Allergy Clin Immunol. 2006;6:443–448.

    PubMed  Article  Google Scholar 

  4. Subbarayan A, Colarusso G, Hughes SM, Gennery AR, Slatter M, Cant AJ, et al. Clinical features that identify children with primary immunodeficiency diseases. Pediatrics. 2011;127:810–816.

    PubMed  Article  Google Scholar 

  5. Slatter MA, Gennery AR. Clinical immunology review series: an approach to the patient with recurrent infections in childhood. Clin Exp Immunol. 2008;152:389–396.

    PubMed  Article  CAS  Google Scholar 

  6. Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl PR, Geha R, et al. The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients. Medicine (Baltimore). 2003;82:373–384.

    Article  CAS  Google Scholar 

  7. Berrington JE, Flood TJ, Abinun M, Galloway A, Cant AJ. Unsuspected Pneumocystis carinii pneumonia at presentation of severe primary immunodeficiency. Arch Dis Child. 2000;82:144–147.

    PubMed  Article  CAS  Google Scholar 

  8. Bouma G, Ancliff PJ, Thrasher AJ, Burns SO. Recent advances in the understanding of genetic defects of neutrophil number and function. Br J Haematol. 2010;151:312–326.

    PubMed  Article  CAS  Google Scholar 

  9. Wood P, Stanworth S, Burton J, Jones A, Peckham DG, Green T, et al. UK Primary Immunodeficiency Network. Recognition, clinical diagnosis and management of patients with primary antibody deficiencies: a systematic review. Clin Exp Immunol. 2007;149:410–423.

    PubMed  Article  CAS  Google Scholar 

  10. Zi Yin E, Frush DP, Donnelly LF, Buckleyl RH. Primary immunodeficiency disorders in pediatric patients: Clinical features and imaging findings. Am J Roentgeno. 2001;176:1541–1552.

    Article  Google Scholar 

  11. Woellner C, Gertz EM, Schäffer AA, Lagos M, Perro M, Glocker EO, et al. Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome. J Allergy Clin Immunol. 2010;125:424–432.

    PubMed  Article  CAS  Google Scholar 

  12. Zhang Q, Davis JC, Lamborn IT, Freeman AF, Jing H, Favreau AJ, et al. Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med. 2009;361:2046–2055.

    PubMed  Article  CAS  Google Scholar 

  13. Buckley RH. The Hyper-IgE syndrome. Clin Rev Allergy Immunol. 2001;20:139–154.

    PubMed  Article  CAS  Google Scholar 

  14. Freeman AF, Collura-Burke CJ, Patronas NJ, Ilcus LS, Darnell D, Davis J, et al. Brain abnormalities in patients with hyperimmunoglobulin E syndrome. Pediatrics. 2007;119:e1121–1125.

    PubMed  Article  Google Scholar 

  15. Albert MH, Notarangelo LD, Ochs HD. Clinical spectrum, pathophysiology and treatment of the Wiskott-Aldrich syndrome. Curr Opin Hematol. 2010. Nov 11. [Epub ahead of print]

    Google Scholar 

  16. Madkaikar M, Currimbhoy Z, Gupta M, Desai M, Rao M. Clinical profile of leukocyte adhesion deficiency. Indian Pediatr. 2011;49:1–4.

    Google Scholar 

  17. Holland SM. Chronic granulomatous disease. Clin Rev Allergy Immunol. 2010;38:3–10.

    PubMed  Article  CAS  Google Scholar 

  18. Al-Muhsen S, Casanova JL. The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases. J Allergy Clin Immunol. 2008;122:1043–1051.

    PubMed  Article  CAS  Google Scholar 

  19. Madkaikar M, Mhatre S, Gupta M, Ghosh K. Advances in autoimmune lymphoproliferative syndromes. Eur J Haematol. 2011;87:1–9.

    PubMed  Article  CAS  Google Scholar 

  20. Dessinioti C, Stratigos AJ, Rigopoulos D, Katsambas AD. A review of genetic disorders of hypopigmentation: lessons learned from the biology of melanocytes. Exp Dermatol. 2009;18:741–749.

    PubMed  Article  CAS  Google Scholar 

  21. Teachey D, Manno CS, Axsom KM, Andrews T, Choi JK, Greenbaum BH, et al. Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS). Blood. 2005;105:2443.

    PubMed  Article  CAS  Google Scholar 

  22. Melaranci C, Ciaffi P, Zerella A, Martinelli V, Cutrera R, Plebani A, et al. T cell subpopulation in paediatric healthy children: age-normal values. J Clin Lab Immunol. 1992;38:143–149.

    PubMed  CAS  Google Scholar 

  23. Walshe D, Gaspar HB, Thrasher AJ, Cale CM, Gilmour KC. Signal transducer and activator of transcription 5 tyrosine phosphorylation for the diagnosis and monitoring of patients with severe combined immunodeficiency. J Allergy Clin Immunol. 2009;123:505–508.

    PubMed  Article  CAS  Google Scholar 

  24. Henter J, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2006;48:124–131.

    Article  Google Scholar 

  25. Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr. 2007;166:95–100.

    PubMed  Article  Google Scholar 

  26. Caminha I, Fleisher TA, Hornung RL, Dale JK, Niemela JE, Price S, et al. Utilizing biomarkers to predict the presence of FAS mutations in patients with features of the autoimmune lymphoproliferative syndrome. J Allergy Clin Immunol. 2010;125:946–949.

    PubMed  Article  CAS  Google Scholar 

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Affiliations

  1. Department of Pediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), KEM Hospital, 13th Floor, NMS Bldg, Parel, Mumbai, India

    Manisha Madkaikar, A. Mishra & K. Ghosh

  2. National Institute of Immunohaematology, KEM Hospital, 13th Floor, NMS Bldg, Parel, Mumbai, 400 012, India

    Manisha Madkaikar

Authors
  1. Manisha Madkaikar
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  2. A. Mishra
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  3. K. Ghosh
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Correspondence to Manisha Madkaikar.

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Madkaikar, M., Mishra, A. & Ghosh, K. Diagnostic approach to primary immunodeficiency disorders. Indian Pediatr 50, 579–586 (2013). https://doi.org/10.1007/s13312-013-0171-4

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  • DOI: https://doi.org/10.1007/s13312-013-0171-4

Key words

  • Antibody deficiency
  • Phagocytic defects
  • Immune dysregulation
  • Primary immunodeficiency disorders
  • Severe combined immunodeficiency (SCID)