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ICON: The Early Diagnosis of Congenital Immunodeficiencies

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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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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Keywords

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