Journal of Clinical Immunology

, Volume 34, Issue 4, pp 398–424 | Cite as

ICON: The Early Diagnosis of Congenital Immunodeficiencies

  • John RoutesEmail author
  • Mario Abinun
  • Waleed Al-Herz
  • Jacinta Bustamante
  • Antonio Condino-Neto
  • Maria Teresa De La Morena
  • Amos Etzioni
  • Eleonora Gambineri
  • Elie Haddad
  • Lisa Kobrynski
  • Francoise Le Deist
  • Shigeaki Nonoyama
  • Joao Bosco Oliveira
  • Elena Perez
  • Capucine Picard
  • Nima Rezaei
  • John Sleasman
  • Kathleen E. Sullivan
  • Troy Torgerson
Key Review Article


Primary immunodeficiencies are intrinsic defects in the immune system that result in a predisposition to infection and are frequently accompanied by a propensity to autoimmunity and/or immunedysregulation. Primary immunodeficiencies can be divided into innate immunodeficiencies, phagocytic deficiencies, complement deficiencies, disorders of T cells and B cells (combined immunodeficiencies), antibody deficiencies and immunodeficiencies associated with syndromes. Diseases of immune dysregulation and autoinflammatory disorder are many times also included although the immunodeficiency in these disorders are often secondary to the autoimmunity or immune dysregulation and/or secondary immunosuppression used to control these disorders. Congenital primary immunodeficiencies typically manifest early in life although delayed onset are increasingly recognized. The early diagnosis of congenital immunodeficiencies is essential for optimal management and improved outcomes. In this International Consensus (ICON) document, we provide the salient features of the most common congenital immunodeficiencies.


Primary immunodeficiencies combined immunodeficiencies severe combined immunodeficiencies diagnosis treatment consensus global-consensus 



Autosomal dominant anhidrotic ectodermal dysplasia with immunodeficiency


Autosomal dominant hyper IgE syndrome


Autosomal recessive hyper IgE syndrome


Ataxia telangiectasia


Ataxia-telangiectasia mutated


Bacillus Calmette-Guérin


Chronic granulomatous disease


Combined immunodeficiencies


Chronic Mucocutaneous Candidiasis


Class switch recombination




Anhidrotic ectodermal dysplasia


Granulocyte colony-stimulating factor


Graft-versus-host disease


Hematopoietic stem-cell transplantation


Herpes simplex encephalitis


Herpes simplex virus type 1


International consensus


Intravenous immunoglobulin


Leukocyte adhesion deficiency type I


Leukocyte adhesion deficiency type II


Leukocyte adhesion deficiency type III


Mendelian susceptibility to mycobacterial diseases


Newborn screening


Nitroblue tetrazolium


Oncostatin M


Primary immunodeficiency


Severe combined immunodeficiency


Somatic hyper mutation


Signal transducer and activator of transcription 3




Toll-like receptors


T cell receptor excision circle


Wiskott-Aldrich syndrome


Wiskott-Aldrich syndrome protein


X-linked hyper IgM


X-linked agammaglobulinemia


X-linked thrombocytopenia


X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency



We thank Dr. Ann Puel, Dr. Shen-Ying Zhang and Pr. Jean-Laurent Casanova for helpful discussions and advice and Dana Gudel and Audrey Harrington for expert secretarial assistance and editing.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • John Routes
    • 1
    • 22
    Email author
  • Mario Abinun
    • 2
  • Waleed Al-Herz
    • 3
  • Jacinta Bustamante
    • 4
  • Antonio Condino-Neto
    • 5
  • Maria Teresa De La Morena
    • 6
  • Amos Etzioni
    • 7
  • Eleonora Gambineri
    • 8
  • Elie Haddad
    • 9
  • Lisa Kobrynski
    • 10
  • Francoise Le Deist
    • 11
  • Shigeaki Nonoyama
    • 12
  • Joao Bosco Oliveira
    • 13
  • Elena Perez
    • 14
  • Capucine Picard
    • 15
    • 16
  • Nima Rezaei
    • 17
    • 18
  • John Sleasman
    • 19
  • Kathleen E. Sullivan
    • 20
  • Troy Torgerson
    • 21
  1. 1.Department of PediatricsMedical College of Wisconsin, and Children’s Research InstituteMilwaukeeUSA
  2. 2.Department of Pediatric Immunology, BMT Unit, Great North Children’s HospitalNewcastle upon Tyne Hospitals NHS Foundation TrustNewcastle upon TyneUK
  3. 3.Department of Pediatrics, Faculty of MedicineKuwait UniversitySafatKuwait
  4. 4.Laboratory of Human Genetics of Infectious Diseases, Necker BranchInstitut National de la Santé et de la Recherche MédicaleParisFrance
  5. 5.Department of Immunology, Institute of Biomedical SciencesUniversity of São PauloSão PauloBrazil
  6. 6.Department of PediatricsThe University of Texas Southwestern Medical CenterDallasUSA
  7. 7.Department of PediatricsRambam Medical Centre and B. Rappaport School of Medicine, TechnionHaifaIsrael
  8. 8.Department of Sciences for Woman and Child’s Health, Anna Meyer Children’s Hospital, Haematology-Oncology Department, BMT UnitUniversity of FlorenceFlorenceItaly
  9. 9.Department of Pediatrics and Department of Microbiology and ImmunologyUniversity of Montreal, CHU Sainte-Justine Research CenterMontrealCanada
  10. 10.Department of PediatricsEmory UniversityAtlantaUSA
  11. 11.Department of Microbiology and Immunology and Department of PediatricsUniversity of Montreal, CHU Sainte-Justine Research CenterMontrealCanada
  12. 12.Department of PediatricsNational Defense Medical CollegeTokorozawaJapan
  13. 13.Instituto de Medicina Integral Prof. Fernando Figueira-IMIPRecifeBrazil
  14. 14.Department of PediatricsUniversity of Miami Miller School of MedicineMiamiUSA
  15. 15.Study Center of Primary ImmunodeficienciesAssistance Publique Hôpitaux de Paris, Necker HospitalParisFrance
  16. 16.Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Imagine Institute, Necker Medical SchoolParis Descartes UniversityParisEU
  17. 17.Research Center for Immunodeficiencies, Children’s Medical CenterTehranIran
  18. 18.Department of Immunology, School of MedicineTehran University of Medical SciencesTehranIran
  19. 19.Division of Allergy and ImmunologyDuke University School of MedicineDurhamUSA
  20. 20.Division of Allergy and ImmunologyThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  21. 21.University of Washington School of MedicineSeattleUSA
  22. 22.Medical College of WisconsinMACC Fund Research CenterMilwaukeeUSA

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