Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency

Abstract

We report the updated classification of primary immunodeficiencies (PIDs) compiled by the Expert Committee of the International Union of Immunological Societies. In comparison to the previous version, more than 30 new gene defects are reported in this updated version. In addition, we have added a table of acquired defects that are phenocopies of PIDs. For each disorder, the key clinical and laboratory features are provided. This classification is the most up-to-date catalog of all known PIDs and acts as a current reference of the knowledge of these conditions and is an important aid for the molecular diagnosis of patients with these rare diseases.

Human genetic basis of interindividual variability in the course of infection

“…Other spectacular achievements have been made in the domain of therapy, including the first successful cases of hematopoietic stem cell transplantation in 1968 (118) and gene therapy in 2000 (119). Increasingly diverse clinical phenotypes, extending beyond infection and including various autoinflammatory, allergic, and autoimmune phenotypes, have been attributed to primary immunodeficiencies (120)(121)(122)(123)(124). Autoimmune phenotypes include systemic and organ-specific conditions such as the intriguingly related and occasionally allelic systemic lupus erythematosus and neurological Aicardi-Goutières syndrome, two type I interferonopathies (125).…”

Streptococcus pneumoniae antibody titres in patients with primary antibody deficiency receiving intravenous immunoglobulin (IVIG) compared to subcutaneous immunoglobulin (SCIG)

“…Patients with known primary immunodeficiency disorders (PIDD) [6] who were receiving either intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) were enrolled during 2014-15 from the Pediatric Allergy and Immunology Clinic at Cardinal Glennon Children's Medical Center at Saint Louis University. Twenty-four subjects with PIDD were enrolled, which included X-linked agammaglobulinaemia (XLA, n 5 6), common variable immunodeficiency (CVID, n 5 9), specific antibody deficiency (SAD, n 5 7) and persistent hypogammaglobulinaemia in patients with severe combined immunodeficiency following transplantation (SCID, n 5 2).…”

Common variable immunodeficiency and idiopathic primary hypogammaglobulinemia: two different conditions within the same disease spectrum

“…Clinical data were collected from all IPH and CVID patients to record their clinical phenotypes as previously described by Chapel et al 2,5 These phenotypes are: 1) no disease-related complications (infections only); 2) autoimmune cytopenias; 3) polyclonal lymphoproliferation (granuloma/LIP/persistent unexplained lympadenopathy); and 4) unexplained persistent enteropathy. In addition, data were collected concerning the frequency and severity of infections and modes of treatment.…”

“…Remarkably, according to the primary immunodeficiency classification of the International Union of Immunological Societies (IUIS) these patients cannot be sufficiently classified within any of the subcategories of "Predominantly Antibody Deficiency". 5 In comparison, the International Classification of Diseases v10 (ICD10), 6 classifies IPH as "hypogammaglobulinemia not otherwise specified" with the same ICD10 code as CVID. Patients Patients with hypogammaglobulinemia who do not fulfill all the classical diagnostic criteria for common variable immunodeficiency (reduction of two immunoglobulin isotypes and a reduced response to vaccination) constitute a diagnostic and therapeutic dilemma, because information concerning the clinical and immunological characteristics of these patients with idiopathic primary hypogammaglobulinemia is not available.…”