Scleroderma, also known as systemic sclerosis, is a chronic systemic autoimmune disease. It is characterised by fibrosis or hardening of the skin, lungs, gastrointestinal tract and/or heart with endothelial dysfunction and a proliferative vasculopathy primarily affecting small blood vessels and capillaries. Patients often present with multiple autoantibodies, including antitopoisomerase I, anticentromere and anti-RNA polymerase III antibodies. In addition, patients have elevated levels of Th2 cytokines. Skin biopsies of scleroderma patients show perivascular infiltrates of mononuclear inflammatory cells.
Scleroderma occurs in genetically susceptible individuals who have encountered specific environmental triggers. Genome wide associated studies have implicated a number of candidate genes in the pathogenesis of the disease. Principle amongst these are HLA class II genes. Strong correlations have been demonstrated between certain HLA-class II alleles and each of the Scleroderma specific autoantibodies.
Scleroderma with anticentromere autoantibodies has been shown to be associated with HLA-DQB1*05:01 and other DQB1 alleles encoding non-leucine residues at position 26 in the peptide binding groove.
Scleroderma with antitopoisomerase I autoantibodies has been shown to be associated with HLA-DRB1*11, especially the DRB1*11:04 and DQB1*03:01 in Caucasian subjects and DRB1*15:02 and DQB1*06:01 in Japanese and Korean subjects.
Scleroderma with anti-RNA polymerase III antibodies has been shown to be associated with HLA-DRB1*13:02 and DQB1*06:04.
A number of other candidate genes outside of HLA, such as connective tissue growth factor, have also been tested for association with scleroderma.
Genetic testing in Scleroderma may be of value in providing insights into the mechanism of the disease, thereby potentially suggesting strategies for prevention and treatment.
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