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ICON: The Early Diagnosis of Congenital Immunodeficiencies

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Abstract

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.

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Abbreviations

AD-EDA-ID:

Autosomal dominant anhidrotic ectodermal dysplasia with immunodeficiency

AD-HIES:

Autosomal dominant hyper IgE syndrome

AR-HIES:

Autosomal recessive hyper IgE syndrome

AT:

Ataxia telangiectasia

ATM:

Ataxia-telangiectasia mutated

BCG:

Bacillus Calmette-Guérin

CGD:

Chronic granulomatous disease

CID:

Combined immunodeficiencies

CMC:

Chronic Mucocutaneous Candidiasis

CSR:

Class switch recombination

DHR:

Dihydrorhodamine–1,2,3

EDA:

Anhidrotic ectodermal dysplasia

G-CSF:

Granulocyte colony-stimulating factor

GVHD:

Graft-versus-host disease

HSCT:

Hematopoietic stem-cell transplantation

HSE:

Herpes simplex encephalitis

HSV1:

Herpes simplex virus type 1

ICON:

International consensus

IVIG:

Intravenous immunoglobulin

LAD-I:

Leukocyte adhesion deficiency type I

LAD-II:

Leukocyte adhesion deficiency type II

LAD-III:

Leukocyte adhesion deficiency type III

MSMD:

Mendelian susceptibility to mycobacterial diseases

NBS:

Newborn screening

NBT:

Nitroblue tetrazolium

OSM:

Oncostatin M

PID:

Primary immunodeficiency

SCID:

Severe combined immunodeficiency

SHM:

Somatic hyper mutation

STAT3:

Signal transducer and activator of transcription 3

TIR:

Toll-IL-1R

TLR:

Toll-like receptors

TREC:

T cell receptor excision circle

WAS:

Wiskott-Aldrich syndrome

WASp:

Wiskott-Aldrich syndrome protein

XHIGM:

X-linked hyper IgM

XLA:

X-linked agammaglobulinemia

XLT:

X-linked thrombocytopenia

XR-EDA-ID:

X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency

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Acknowledgments

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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Authors and Affiliations

  1. Department of Pediatrics, Medical College of Wisconsin, and Children’s Research Institute, Milwaukee, WI, 53226-4874, USA

    John Routes

  2. Department of Pediatric Immunology, BMT Unit, Great North Children’s Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

    Mario Abinun

  3. Department of Pediatrics, Faculty of Medicine, Kuwait University, Safat, Kuwait

    Waleed Al-Herz

  4. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Paris, France

    Jacinta Bustamante

  5. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

    Antonio Condino-Neto

  6. Department of Pediatrics, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-9063, USA

    Maria Teresa De La Morena

  7. Department of Pediatrics, Rambam Medical Centre and B. Rappaport School of Medicine, Technion, Haifa, Israel

    Amos Etzioni

  8. Department of Sciences for Woman and Child’s Health, Anna Meyer Children’s Hospital, Haematology-Oncology Department, BMT Unit, University of Florence, Viale Gaetano Pieraccini, 24, 50139, Florence, Italy

    Eleonora Gambineri

  9. Department of Pediatrics and Department of Microbiology and Immunology, University of Montreal, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada

    Elie Haddad

  10. Department of Pediatrics, Emory University, Atlanta, GA, USA

    Lisa Kobrynski

  11. Department of Microbiology and Immunology and Department of Pediatrics, University of Montreal, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada

    Francoise Le Deist

  12. Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan

    Shigeaki Nonoyama

  13. Instituto de Medicina Integral Prof. Fernando Figueira-IMIP, Recife, PE, Brazil

    Joao Bosco Oliveira

  14. Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, USA

    Elena Perez

  15. Study Center of Primary Immunodeficiencies, Assistance Publique Hôpitaux de Paris, Necker Hospital, 75015, Paris, France

    Capucine Picard

  16. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Imagine Institute, Necker Medical School, Paris Descartes University, Paris, France, EU

    Capucine Picard

  17. Research Center for Immunodeficiencies, Children’s Medical Center, Tehran, Iran

    Nima Rezaei

  18. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

  19. Division of Allergy and Immunology, Duke University School of Medicine, DUMC Box 2644, 203 Research Dr. Room 133B MSRB 1, Durham, NC, 27710, USA

    John Sleasman

  20. Division of Allergy and Immunology, The Children’s Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, PA, 19104-4399, USA

    Kathleen E. Sullivan

  21. University of Washington School of Medicine, 1900 9th Ave., C9S-7, Seattle, WA, 98101-1304, USA

    Troy Torgerson

  22. Medical College of Wisconsin, MACC Fund Research Center, Room 5064, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA

    John Routes

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  1. John Routes
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Correspondence to John Routes.

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Routes, J., Abinun, M., Al-Herz, W. et al. ICON: The Early Diagnosis of Congenital Immunodeficiencies. J Clin Immunol 34, 398–424 (2014). https://doi.org/10.1007/s10875-014-0003-x

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  • DOI: https://doi.org/10.1007/s10875-014-0003-x

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