Pathogenesis of rheumatoid arthritis. Part I: acquired immunity, genetic and environmental factors

In rheumatoid arthritis (RA), clinical symptoms are preceded by the asymptomatic phase when autoimmune response of various specificities is initiated. The most characteristic is reactivity of T and B lymphocytes to citrullinated self-proteins. Development of autoimmune response is determined by genetic and environmental factors. Genetic background is formed by polymorphic HLA-DRB1 gene, encoding DR molecules with a “shared epitope” which present autoantigens, and by numerous genes associated with adaptive immunity. Cigarette smoking and infections with Porphyromonas gingivalis , known to trigger protein citrullination, are considered to be the major environmental factors. Autoimmunity alone is insufficient to trigger the disease, but represents an important component of pathological processes because autoantibodies and activated lymphocytes participate in the initiation and support of inflammation and in the joint destruction. Based on recently published data these questions are discussed, summarized and presented graphically (Fig. 1). The role of innate immunity, cytokines and destruction processes in RA pathogenesis will be the subject of next review articles.