Preclinical rheumatoid arthritis: A modern view of the pathogenesis and possibilities of prevention

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a multifactorial pathogenetic basis, characterized by progressive development preceding clinical manifestation. This review examines the natural history of the disease, including stages from genetic predisposition and exposure to external provoking factors to the formation of preclinical autoimmunity and subsequent inflammatory joint damage. The central role in pathogenesis is played by the interaction of key genetic determinants, such as HLA-DRB1 alleles, with exogenous triggers, including smoking and infectious agents, leading to the production of specific autoantibodies – anticitrullinated protein antibodies and rheumatoid factor. These serological markers can be recorded years before the onset of joint symptoms, indicating a long preclinical period of the disease. Prodromal stages of RA, accompanied by systemic inflammation and immune dysregulation, are considered as critical “windows of opportunity” for preventive measures aimed at preventing the disease from progressing to a clinically expressed phase. Of particular importance are studies aimed at restoring immunological tolerance and modulating microbiomes, which opens up prospects for the development of innovative therapeutic approaches. These strategies should be aimed at preventing disease at the earliest stages of its pathogenesis, long before clinical manifestation. In addition, the development of methods for visualizing subclinical changes and refining risk stratification criteria will be critical for identifying individuals in need of targeted measures. Current strategies of primary and secondary prevention include risk factor modification (smoking cessation, microbiome and diet correction). These approaches offer prospects for reducing the incidence of RA among individuals with a genetic predisposition or the presence of immunological markers in the preclinical stage of the disease.