title: Genetic insights into disease mechanisms of autoimmunity.
abstract: Educating the immune system to distinguish between self and non-self is critical to ensure that an immune response is mounted against foreign antigens and not against self. A breakdown in these mechanisms can lead to the onset of autoimmune disease. Clinical and molecular data suggest that shared immunogenetic mechanisms lead to the autoimmune process. The most studied genes and molecules are the human leukocyte antigen (HLA) region and the cytotoxic T-lymphocyte-associated 4 molecule (CTLA-4). Recently progress has been achieved in narrowing down the primary variants within both gene regions, but further work is needed to determine the function and extent of the aetiological variant(s) present. Recent exciting results also suggest a role for the newly discovered lymphoid-specific phosphatase (LYP) protein. As well as these general mechanisms, disease-specific mechanisms are beginning to be elucidated, for example the role of autoimmune regulatory element 1 (AIRE1) in autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy (APECED). Taken together, these data suggest that both general and disease-specific mechanisms lead to the clinical outcome of autoimmune disease and that increased understanding of these mechanisms will improve our knowledge of how autoimmune disease occurs, eventually leading to the development of novel therapeutic agents.
authors.affiliation: Division of Medical Sciences, University of Birmingham, Institute of Biomedical Research, Birmingham B15 2TT, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Simmonds
authors.forename: S C L
authors.initials: SC
authors.lastname: Gough
mesh_terms: D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology; D060908:CTLA-4 Antigen; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology; D007328:Insulin / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D000096927:AIRE Protein
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; D003165:Complement System Proteins; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007328:Insulin; D014157:Transcription Factors; D000096927:AIRE Protein; C556706:CTLA4 protein, human