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Aicardi-Goutières syndrome: a model disease for systemic autoimmunity.
- Source :
-
Clinical and experimental immunology [Clin Exp Immunol] 2014 Jan; Vol. 175 (1), pp. 17-24. - Publication Year :
- 2014
-
Abstract
- Systemic autoimmunity is a complex disease process that results from a loss of immunological tolerance characterized by the inability of the immune system to discriminate self from non-self. In patients with the prototypic autoimmune disease systemic lupus erythematosus (SLE), formation of autoantibodies targeting ubiquitous nuclear antigens and subsequent deposition of immune complexes in the vascular bed induces inflammatory tissue injury that can affect virtually any organ system. Given the extraordinary genetic and phenotypic heterogeneity of SLE, one approach to the genetic dissection of complex SLE is to study monogenic diseases, for which a single gene defect is responsible. Considerable success has been achieved from the analysis of the rare monogenic disorder Aicardi-Goutières syndrome (AGS), an inflammatory encephalopathy that clinically resembles in-utero-acquired viral infection and that also shares features with SLE. Progress in understanding the cellular and molecular functions of the AGS causing genes has revealed novel pathways of the metabolism of intracellular nucleic acids, the major targets of the autoimmune attack in patients with SLE. Induction of autoimmunity initiated by immune recognition of endogenous nucleic acids originating from processes such as DNA replication/repair or endogenous retro-elements represents novel paradigms of SLE pathogenesis. These findings illustrate how investigating rare monogenic diseases can also fuel discoveries that advance our understanding of complex disease. This will not only aid the development of improved tools for SLE diagnosis and disease classification, but also the development of novel targeted therapeutic approaches.<br /> (© 2013 British Society for Immunology.)
- Subjects :
- Animals
Autoantibodies genetics
Autoantibodies immunology
Disease Models, Animal
Humans
Autoimmune Diseases of the Nervous System genetics
Autoimmune Diseases of the Nervous System immunology
Autoimmune Diseases of the Nervous System pathology
Autoimmune Diseases of the Nervous System therapy
Autoimmunity genetics
DNA genetics
DNA immunology
DNA Repair genetics
DNA Repair immunology
DNA Replication genetics
DNA Replication immunology
Lupus Erythematosus, Systemic genetics
Lupus Erythematosus, Systemic immunology
Lupus Erythematosus, Systemic pathology
Lupus Erythematosus, Systemic therapy
Nervous System Malformations genetics
Nervous System Malformations immunology
Nervous System Malformations pathology
Nervous System Malformations therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2249
- Volume :
- 175
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Clinical and experimental immunology
- Publication Type :
- Academic Journal
- Accession number :
- 23786362
- Full Text :
- https://doi.org/10.1111/cei.12160