A similar preclinical RA study [220] showed no detectable cytokine more than 5 years before RA onset, but during the 5-year interval before diagnosis, increased levels were associated with an increased likelihood of the risk of developing RA (IL-1 alpha, IL-1beta, IL-1RA, IL-4, IL-10, TNF-alpha, and soluble TNF-RI). The gene discussed is TNF; the disease is rheumatoid arthritis.