The etiology and pathogenesis of RA are complex and multifaceted. A range of predetermined (genes) and stochastic (random events and environment) factors contribute to susceptibility and pathogenesis.(kelly). The initiation of RA probably begins years before the onset of clinical symptoms. This process involves certain specific genes that can help break tolerance and lead to autoreactivity. It is likely that the earliest phases are marked by repeated activation of innate immunity Cigarette smoke, bacterial products, viral components, and other environmental stimuli can contribute to these responses. In individuals, a predetermined propensity for immune hyper-reactivity or autoreactivity might lead to a different outcome. The genome of these
