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Primary Immunodeficiency Diseases

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Book cover Critical Care of the Pediatric Immunocompromised Hematology/Oncology Patient

Abstract

Primary immunodeficiency diseases (PIDs) are a heterogeneous group of monogenic disorders in which part of the immune system is deficient or does not function properly. Patients with PID commonly present with recurrent infections, which explains the importance of the immune system in protection from organisms. PIDs are classified according to the affected component of the immune system into innate immunity disorders and adaptive immunity disorders. Early diagnosis and aggressive management ranging from medical treatment to stem cell transplantation are crucial to decrease disease-associated morbidity and mortality. In this review, we will provide a detailed overview of classification, diagnosis, and treatments of PIDs, with particular attention to the critical care management of the common complications of these rare diseases.

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References

  1. Medzhitov R, Janeway C Jr. Innate immune recognition: mechanisms and pathways. Immunol Rev. 2000;173:89–97.

    Article  CAS  Google Scholar 

  2. Cooper MD, Alder MN. The evolution of adaptive immune systems. Cell. 2006;124(4):815–22.

    Article  CAS  Google Scholar 

  3. Picard C, et al. International union of immunological societies: 2017 primary immunodeficiency diseases committee report on inborn errors of immunity. J Clin Immunol. 2018;38(1):96–128.

    Article  Google Scholar 

  4. Bousfiha A, et al. Primary immunodeficiencies of protective immunity to primary infections. Clin Immunol. 2010;135(2):204–9.

    Article  CAS  Google Scholar 

  5. Turvey SE, Broide DH. Innate immunity. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S24–32.

    Article  Google Scholar 

  6. Bonilla FA, Oettgen HC. Adaptive immunity. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S33–40.

    Article  Google Scholar 

  7. Notarangelo LD. Primary immunodeficiencies. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S182–94.

    Article  Google Scholar 

  8. Leiding JW, Holland SM. Chronic granulomatous disease. In: Adam MP, et al., editors. GeneReviews((R)). Seattle: University of Washington; 1993.

    Google Scholar 

  9. Etzioni A. Defects in the leukocyte adhesion cascade. Clin Rev Allergy Immunol. 2010;38(1):54–60.

    Article  CAS  Google Scholar 

  10. Frank MM. Complement deficiencies. Pediatr Clin N Am. 2000;47(6):1339–54.

    Article  CAS  Google Scholar 

  11. Al-Muhsen S, Casanova JL. The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases. J Allergy Clin Immunol. 2008;122(6):1043–51. quiz 1052–3.

    Article  CAS  Google Scholar 

  12. Conley ME, et al. Primary B cell immunodeficiencies: comparisons and contrasts. Annu Rev Immunol. 2009;27:199–227.

    Article  CAS  Google Scholar 

  13. Fischer A, et al. Severe combined immunodeficiencies and related disorders. Nat Rev Dis Primers. 2015;1:15061.

    Article  Google Scholar 

  14. Shearer WT, et al. Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience. J Allergy Clin Immunol. 2014;133(4):1092–8.

    Article  Google Scholar 

  15. Ohashi PS. Negative selection and autoimmunity. Curr Opin Immunol. 2003;15(6):668–76.

    Article  CAS  Google Scholar 

  16. Peterson P, et al. APECED: a monogenic autoimmune disease providing new clues to self-tolerance. Immunol Today. 1998;19(9):384–6.

    Article  CAS  Google Scholar 

  17. Sakaguchi S, et al. Pillars article: immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 1995. J Immunol. 2011;186(7):3808–21.

    Google Scholar 

  18. Alroqi FJ, Chatila TA. T regulatory cell biology in health and disease. Curr Allergy Asthma Rep. 2016;16(4):27.

    Article  Google Scholar 

  19. Rieux-Laucat F. Inherited and acquired death receptor defects in human Autoimmune Lymphoproliferative Syndrome. Curr Dir Autoimmun. 2006;9:18–36.

    CAS  PubMed  Google Scholar 

  20. Oliveira JB, Fleisher TA. Laboratory evaluation of primary immunodeficiencies. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S297–305.

    Article  Google Scholar 

  21. Bonilla FA, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136(5):1186–205.e1–78.

    Article  Google Scholar 

  22. Aguilar C, et al. Prevention of infections during primary immunodeficiency. Clin Infect Dis. 2014;59(10):1462–70.

    Article  CAS  Google Scholar 

  23. Buckley RH. Pulmonary complications of primary immunodeficiencies. Paediatr Respir Rev. 2004;5(Suppl A):S225–33.

    Article  Google Scholar 

  24. Yazdani R, et al. Infectious and noninfectious pulmonary complications in patients with primary immunodeficiency disorders. J Investig Allergol Clin Immunol. 2017;27(4):213–24.

    Article  CAS  Google Scholar 

  25. Chase NM, et al. Use of combination chemotherapy for treatment of granulomatous and lymphocytic interstitial lung disease (GLILD) in patients with common variable immunodeficiency (CVID). J Clin Immunol. 2013;33(1):30–9.

    Article  CAS  Google Scholar 

  26. Janka GE, Lehmberg K. Hemophagocytic syndromes – an update. Blood Rev. 2014;28(4):135–42.

    Article  Google Scholar 

  27. Henter JI, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124–31.

    Article  Google Scholar 

  28. Bode SF, et al. The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis. Haematologica. 2015;100(7):978–88.

    Article  Google Scholar 

  29. Bergsten E, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017;130(25):2728–38.

    Article  CAS  Google Scholar 

  30. Vadyvaloo V, et al. Transit through the flea vector induces a pretransmission innate immunity resistance phenotype in Yersinia pestis. PLoS Pathog. 2010;6(2):e1000783.

    Article  Google Scholar 

  31. Rae W, et al. Autoimmunity/inflammation in a monogenic primary immunodeficiency cohort. Clin Transl Immunol. 2017;6(9):e155.

    Article  Google Scholar 

  32. Vignesh P, Rawat A, Singh S. An update on the use of immunomodulators in primary immunodeficiencies. Clin Rev Allergy Immunol. 2017;52(2):287–303.

    Article  CAS  Google Scholar 

  33. Villa A, Notarangelo LD, Roifman CM. Omenn syndrome: inflammation in leaky severe combined immunodeficiency. J Allergy Clin Immunol. 2008;122(6):1082–6.

    Article  CAS  Google Scholar 

  34. Wahlstrom J, et al. Transplacental maternal engraftment and posttransplantation graft-versus-host disease in children with severe combined immunodeficiency. J Allergy Clin Immunol. 2017;139(2):628–633.e10.

    Article  CAS  Google Scholar 

  35. Muller SM, et al. Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients. Blood. 2001;98(6):1847–51.

    Article  CAS  Google Scholar 

  36. Palmer K, et al. Unusual clinical and immunologic manifestations of transplacentally acquired maternal T cells in severe combined immunodeficiency. J Allergy Clin Immunol. 2007;120(2):423–8.

    Article  CAS  Google Scholar 

  37. Sebnem Kilic S, Kavurt S, Balaban Adim S. Transfusion-associated graft-versus-host disease in severe combined immunodeficiency. J Investig Allergol Clin Immunol. 2010;20(2):153–6.

    CAS  PubMed  Google Scholar 

  38. Walter JE, et al. Mechanism-based strategies for the management of autoimmunity and immune dysregulation in primary immunodeficiencies. J Allergy Clin Immunol Pract. 2016;4(6):1089–100.

    Article  Google Scholar 

  39. Odek C, et al. Patients with primary immunodeficiencies in pediatric intensive care unit: outcomes and mortality-related risk factors. J Clin Immunol. 2014;34(3):309–15.

    Article  Google Scholar 

  40. Al-Herz W, Moussa MA. Survival and predictors of death among primary immunodeficient patients: a registry-based study. J Clin Immunol. 2012;32(3):467–73.

    Article  Google Scholar 

  41. Rubin Z, et al. Prevalence and outcomes of primary immunodeficiency in hospitalized children in the United States. J Allergy Clin Immunol Pract. 2018;6(5):1705–10.

    Article  Google Scholar 

  42. Antoine C, et al. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968–99. Lancet. 2003;361(9357):553–60.

    Article  Google Scholar 

  43. Buckley RH. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Annu Rev Immunol. 2004;22:625–55.

    Article  CAS  Google Scholar 

  44. Pai SY, et al. Transplantation outcomes for severe combined immunodeficiency, 2000–2009. N Engl J Med. 2014;371(5):434–46.

    Article  CAS  Google Scholar 

  45. Shin CR, et al. Outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome. Bone Marrow Transplant. 2012;47(11):1428–35.

    Article  CAS  Google Scholar 

  46. Barzaghi F, et al. Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: an international multicenter retrospective study. J Allergy Clin Immunol. 2018;141(3):1036–1049.e5.

    Article  Google Scholar 

  47. Gungor T, 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.

    Article  CAS  Google Scholar 

  48. Seo JJ. Hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis: recent advances and controversies. Blood Res. 2015;50(3):131–9.

    Article  CAS  Google Scholar 

  49. Fischer A, Cavazzana-Calvo M. Gene therapy of inherited diseases. Lancet. 2008;371(9629):2044–7.

    Article  Google Scholar 

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Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pediatric, King Abdullah Specialized Children’s Hospital, Riyadh, Saudi Arabia

    Fayhan Alroqi, Abdulrahman Alsultan & Mohammed Essa

  2. King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia

    Fayhan Alroqi & Mohammed Essa

  3. King Abdullah International Medical Research Center, Riyadh, Saudi Arabia

    Fayhan Alroqi

  4. Department of Pediatric, College of Medicine, King Saud University, Riyadh, Saudi Arabia

    Abdulrahman Alsultan

Authors
  1. Fayhan Alroqi
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  2. Abdulrahman Alsultan
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  3. Mohammed Essa
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Editor information

Editors and Affiliations

  1. Pediatric Hematology-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Christine N. Duncan

  2. Children’s Hospital of Wisconsin-Milwaukee, Medical College of Wisconsin, Milwaukee, WI, USA

    Julie-An M. Talano

  3. Department of Pediatric Medicine, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Jennifer A. McArthur

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Alroqi, F., Alsultan, A., Essa, M. (2019). Primary Immunodeficiency Diseases. In: Duncan, C., Talano, JA., McArthur, J. (eds) Critical Care of the Pediatric Immunocompromised Hematology/Oncology Patient. Springer, Cham. https://doi.org/10.1007/978-3-030-01322-6_5

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  • DOI: https://doi.org/10.1007/978-3-030-01322-6_5

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-01321-9

  • Online ISBN: 978-3-030-01322-6

  • eBook Packages: MedicineMedicine (R0)

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