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.

Overview of Immunodeficiency Disorders

“…International Consensus (ICON) classification of PIDs recognizes the disorders of immune dysregulation and auto inflammation to be separate entities since their immune manifestations may be secondary to the dysregulation or autoimmunity. 5 …”

“…NF-κB pathway defect/Anhidrotic ectodermal dysplasia (EDA) – X-linked NEMO (Online Mendelian inheritance in man or OMIM# 300248), autosomal dominant IKBA (OMIM# 612132) gain of function (GOF) mutation, and autosomal recessive IKBKB mutations can all cause EDA characterized by hypohidrosis, sparse hair, conical teeth and early loss of teeth 5 . Hypogammaglobulinemia with impaired specific antibody production is noted in these defects.…”

“…Patients with IKBA defects are prone to Pneumocystis jirovecii and mucocutaneous candidiasis. 5,7 IKBKB defect presents as SCID with the most common infections being Listeria monocytogenes, Serratia marascens, Escherichia coli, mucocutaneous candidiasis, and parainfluenza 5,8 .…”

Sinopulmonary Complications in Subjects With Primary Immunodeficiency

“…[12][13][14][15][16][17][18] Primary immunodeficiency disorder in Kuwait, a small country located in the Arabian Peninsula, is relatively common with a prevalence of 11.98 in 100,000 children, an incidence of 10.06 in 100,000 children, and an estimated occurrence of 1 in 1,000 live births. 12 This is much higher than the reported prevalence in populations from other ethnicities or geographical regions (eg, 4.4 in 100,000 in France, 19 5.6 in 100,000 in Australia, 20 1.51 in 10,000 in Germany, 21 and 2.3 in 100,000 in Japan 22 ). The high prevalence of primary immunodeficiency disorder in Kuwait is probably caused by the high rate of consanguineous marriages among our population.…”

“…[1][2][3][4] Patients with primary immunodeficiency disorders are more likely to experience recurrent, serious, and unusual infections and have a tendency to develop a wide range of complications. [5][6][7] The true incidence and prevalence of primary immunodeficiency disorders are not known.…”