Genetic and environmental factors seem to be important contributors of disease progression, with influence of sex (more frequent in male), presence of two copies of the HLA-DRB1 "shared epitope" (HLA-DR SE) and anticyclic citrullinated peptide antibody (anti-CCP), and possibly tobacco exposure [106, 107].Almost 50% of patients with RA have specific serologic abnormalities several years before the onset of joint symptoms, and the findings of elevated serum levels of IgM rheumatoid factor or anti-CCP is associated with a high risk for the development of RA [107]. Here, HLA-DRB1 is linked to rheumatoid arthritis.