title: Autoimmunity in severe combined immunodeficiency (SCID): lessons from patients and experimental models.
abstract: Autoimmunity is observed in many immunodeficiencies and is thought to be mediated mainly by persistent infection. Severe combined immunodeficiency (SCID) is the most severe form of immunodeficiency and is also on occasion associated with autoimmune phenomena, usually in the form of the Omenn's Syndrome phenotype. Recent studies both in human and mice shed light into the pathogenesis of these two seemingly different conditions occurring together. Central tolerance, which is in charge of elimination of autoreactive T-cell clones, is defective in SCID because of markedly reduced expression of Aire, a transcriptional regulator for the expression of tissue-specific antigens in the thymus. Peripheral tolerance is also markedly decreased in SCID because of several factors including the expansion of T-cell clones as a consequence of the lymphopenia observed in these condition as well as a diminished number of T regulatory (FOXP3+)cells, allowing autoreactive T cells to proliferate and infiltrate various organs in the body of SCID. It is thus of no surprise when both central and peripheral tolerance are impaired that autoimmunity can be observed in SCID.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIAID, NIH, Bethesda, MD, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Milner
authors.forename: Anders
authors.initials: A
authors.lastname: Fasth
authors.forename: Amos
authors.initials: A
authors.lastname: Etzioni
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D016867:Immunocompromised Host; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D000096927:AIRE Protein
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D000096927:AIRE Protein; C418974:FOXP3 protein, human; C499311:RAG2 protein, human; C064658:RAG-1 protein