title: Autoimmunity in hyper-IgM syndrome.
abstract: BACKGROUND
  Immunodeficiency with hyper-IgM (HIGM) results from genetic defects in the CD40-CD40 ligand (CD40L) pathway or in the enzymes required for immunoglobulin class switch recombination and somatic hypermutation. HIGM can thus be associated with an impairment of both B-cell and T-cell activation.
  
  
  CONCLUSIONS
  There are seven main subtypes of HIGM and the most frequent is X-linked HIGM, resulting from CD40L mutations. In addition to the susceptibility to recurrent and opportunistic infections, these patients are prone to autoimmune manifestations, especially hematologic abnormalities, arthritis, and inflammatory bowel disease. Furthermore, organ-specific autoantibodies are commonly found in HIGM patients.
  
  
  CONCLUSIONS
  The mechanisms by which HIGM associates to autoimmunity are not completely elucidated but a defective development of regulatory T cells, the presence of IgM autoantibodies and an impaired peripheral B-cell tolerance checkpoint have been implicated. This article reviews the main subtypes of HIGM syndrome, the clinical autoimmune manifestations found in these patients, and the possible mechanisms that would explain this association.
authors.affiliation: Pediatric Rheumatology Unit, Pediatrics Department, Universidade de São Paulo, Av. Dr. Enéas Carvalho de Aguiar 500 IMT Bldg. II 3rd floor, São Paulo, Sao Paulo 054030-000, Brazil.
authors.forename: Adriana A
authors.initials: AA
authors.lastname: Jesus
authors.forename: Alberto J S
authors.initials: AJ
authors.lastname: Duarte
authors.forename: João B
authors.initials: JB
authors.lastname: Oliveira
mesh_terms: D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D053306:Hyper-IgM Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D009894:Opportunistic Infections / Q000276:immunology; D017634:Self Tolerance; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D001323:Autoantibodies; D023201:CD40 Ligand