In early RA, biological treatment results in an increased proportion of clinical remission. developing lymphoma when compared with healthy individuals 4. Antibodies play an important role in the pathogenesis of RA, as shown by a study using a mouse model deficient in the Eicosapentaenoic Acid low-affinity inhibitory Fc receptor (FcRIIB). Mice injected with human RA-associated antibodies developed polysynovitis; in contrast, no response was observed using control serum, or in mice which were not deficient in FcRIIB 5. RA is also associated with the presence of anti-citrullinated protein antibodies (ACPAs); citrullinated proteins are those in which the enzyme peptidylarginine deiminase (PAD) has catalyzed the conversion of protein-bound arginine to citrulline via post-translational modification. The fibrinogen protein is particularly susceptible to citrullination, leading to the development of citrullinated fibrinogen (cFb), which has been shown to PTGER2 exacerbate disease in a Eicosapentaenoic Acid mouse RA model 6. When human macrophages are incubated with cFb production of tumour necrosis factor (TNF) is usually induced 7, indicating a potential role for citrullination in the propagation of inflammation in RA. Known risk factors for RA include smoking, which has been shown to induce citrullination in the lungs 8. Citrullination can also be stimulated by the PAD-containing bacteria em Porphyromonas gingivalis /em , which can be found in the oral cavity (where it has been implicated in various forms of periodontal disease 9), as well as by other enzymes in the colon. In addition, some people are genetically predisposed to secrete ACPAs. For example, the role of the normal human leucocyte antigen (HLA) is usually to present peptide antigens to the immune system; however, several HLA-DRB1 alleles share a common sequence motif (called the shared epitope) that binds citrullinated peptides, and are therefore associated with an increase in secretion of ACPAs 10. Therefore, a combination of environmental and genetic triggers can increase the risk of developing RA. ACPAs can aid in the diagnosis of RA, as assays for these autoantibodies have high specificity ( 95%) and sensitivity (50C60%). Moreover, these autoantibodies can be detected years before the patient exhibits any symptoms when the disease is in the early stages, providing Eicosapentaenoic Acid a window of opportunity for early treatment, which is essential to avoid rapid joint destruction. Autoantibodies can also be used to predict a patient’s response to treatment for RA. For example, data from a French registry have shown that patients testing positive for anti-cyclic citrullinated peptide (anti-CCP) had a better response to treatment with abatacept [a fusion protein of human Fc fused to the extracellular domain name of cytotoxic T lymphocyte antigen-4 (CTLA-4)] than patients without anti-CCP 11. Therapeutic monoclonal antibodies are an important element of the therapeutic strategy used to treat RA. A variety of mechanisms can be exploited, such as the inhibition of cytokines, T Eicosapentaenoic Acid cells and B cells. The current treatment strategy for RA consists of methotrexate as first-line therapy. Eicosapentaenoic Acid If this is unsuccessful, then combination therapy with methotrexate and a biological therapy should be considered, followed by third-line therapy with a change in biological therapy or Janus kinase/signal transducer and activator of transcription (JAK/STAT) kinase inhibitors. Biological therapy classes used in RA include inhibitors of cytokines such as anti-TNF [e.g. etanercept, a human recombinant receptor/Fc fusion protein; infliximab, adalimumab and golimumab, monoclonal antibodies (mAb); and certolizumab pegol, a PEGylated humanized Fab fragment] 12, anti-interleukin (IL)-6 receptor (e.g. tocilizumab, a humanized mAb which antagonizes the IL-6 receptor), CTLA-4-Ig (e.g. abatacept, an inhibitor of T cell co-stimulation) or anti-CD20 (e.g. rituximab, a chimeric mAb which depletes B cells). These therapies have a better efficacy to block radiographic progression of RA than methotrexate. Treatment with a combination of methotrexate and biological therapy is more effective than either therapy alone 13. In early RA, biological treatment results in an increased proportion of clinical remission. For example, a randomized, double-blind parallel treatment trial showed that early treatment with etanercept.