Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that mostly attacks synovial joints, although other tissues and organs can be affected. The final effect is usually the destruction of articular cartilage and ankylosis of the joints, with a prevalence of the wrist and small joints of the hand. Diagnostic criteria have recently been revised (Aletaha et al., 2010; Neogi et al., 2010). The prevalence of RA is about 1% in the total population, being women more affected than men in a ratio of approximately 2-3:1 (Alamanos & Drosos, 2005). RA is considered an autoimmune disorder, although the etiology and pathogenesis of the disease remain unclear. A complex set of factors are involved in the onset of the disease, including genetic and environmental. The strongest genetic association is with the genes encoding major histocompatibility complex (MHC, HLA in human) class II molecules (Gregersen et al., 1987; Stastny, 1978), although other genes have been associated with RA, including PTPN22, STAT4, TRAF1/C5, and others. Antibodies against the Fc fraction of IgG are found in the serum of about 80% of patients with RA. These autoantibodies are called rheumatoid factor (RF), and the consideration of RA as an autoimmune disease has largely been based on the presence of RF in the serum of patients. Nevertheless, the presence of RF is not exclusive of RA and that, together with the absence of definitive data demonstrating an arthritogenic effect of RF, suggest that these antibodies are produced as a consequence of the immune response rather than being the cause of it (Nemazee, 1985; Tarkowski et al., 1985). However, the adaptive immune response seems to play an important role in the disease as suggested by the strong association of RA with the presence of some HLA class II alleles. Autoantibodies against citrullinated proteins (ACPAs) have been described in the serum of about 50-70% of RA patients in comparison with about 2% of the healthy population (Avouac et al., 2006; Kroot et al., 2000; Nishimura et al., 2007; Schellekens et al., 2000; van Gaalen et al., 2004; Vincent et al., 2002). The presence of ACPAs is very stable during the course of the disease and is quite specific for RA. These antibodies can be detected several years before of symptomatic disease, making the presence of ACPAs a good clinical marker for RA. Patients containing ACPAs in the serum usually have a more severe disease. The presence of these antibodies correlates very well with the