Current Insights into the Pathogenesis of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a common autoimmune disease that is associated with progressive disability, systemic complications, decreased quality of life, higher mortality rate than healthy individuals and socioeconomic costs. The cause of rheumatoid arthritis is unknown, and the prognosis is guarded. However, advances in understanding the disease pathogenesis have fostered the development of new therapeutics, which have improved disease outcomes. RA is a chronic, progressive disease characterized by synovial inflammation and hyperplasia, autoantibody production (rheumatoid factor, anticitrullinated protein antibody [ACPA] and others), cartilage and bone destruction, and systemic features, including cardiovascular, pulmonary, psychological, and skeletal disorders. RA affects approximately 0.5-1 % of European and North-American adults, with considerable regional differences. Prevalence estimates for Southern European countries are lower than for Northern Europe and highest rates are found in North America. Although some patients have mild self-limited disease, many experience joint destruction, severe physical disability and multiple co-morbidities. Mortality rates are more than twice as high in patients with RA as in the general population and this gap appears to be widening. Although much is known about the etiology and pathogenesis of rheumatoid arthritis (RA), understanding of all involved immune pathways remains incomplete and is due to a complex interplay among genotype, environmental triggers, and chance. This article reviews some of the most important risk factors and elements considered significant in RA pathogenesis, which are genetic susceptibility ( association with class II major histocompatability (MHC) antigens, specifically the shared epitope found in HLA-DR4 which predisposes to the development of ACPA-positive RA), environmental factors (smoking, periodontal disease, gastrointestinal pathogens etc), humoral factors (predominance of female gender, age of menarche) immunological factors responsible for initiating and maintaining inflammation (role of T lymphocytes, B Lymphocytes, inflammatory cytokines, fibroblasts and osteoclasts).