Problems of rheumatoid arthritis immunopathology: evolution of the disease

The review considers new data on the immunopathology of rheumatoid arthritis (RA), with emphasis on the early stage of the disease. The evolution of RA includes several successive (or discrete) stages that culminate in the development of a symptom complex characteristic of RA. However, the nature of the interaction of environmental factors, genetic predisposition, and immune mechanisms that determine the transition from stage to stage, the types of progression, the nature and severity of extra-articular (systemic) manifestations, and the risk of comorbid diseases is not entirely clear and is currently the subject of intensive studies. Hyperproduction of autoantibodies, such as rheumatoid factors and antibodies to proteins subject to posttranslational modification, citrullination, carbamylation, acetylation, etc., occupies an important place among the pathogenetic mechanisms of RA development. Immune response against posttranslationally modified (primarily citrullinated) proteins is a key pathogenetic mechanism for the development of RA in all stages of the disease. New data on the role of anti-citrillinated protein antibodies (anti-CPA) in the development of pain and bone resorption in the absence of inflammation pathogenetically substantiate the existence of a pre-clinical disease phase characterized by arthralgia and autoantibody hyperproduction. In conclusion, the paper considers the new possibilities of preventing RA in high-risk groups (anti-CRA-positive clinically suspect arthralgia), by using methotrexate, the anti-B cell drug rituximab, the T-lymphocyte costimulation blocker abatacept, etc.