Autoantibodies in RA may be present before clinical disease is well known.[31] Recently anti-CCP antibodies are present in the blood years before disease onset; patients were shown to have positive RF and/or anti-CCP on at least once before RA symptoms, a median of 4.5 years before symptom onset.[31] In another similar study by Rantapää-Dahlqvist et al,[32] the prevalence of autoantibodies were 16.9% for IgG-RF, 19.3% for IgM-RF, and 33.7% for anti-CCP, with median 2.5 years before RA. This evidence concerns the gene CD40LG and rheumatoid arthritis.