Immunopathologie de la polyarthrite rhumatoïde

Abstract

Rheumatoid arthritis (RA) is one of the most studied auto-immune disease. In fifty years, considerable progress in the comprehension of the immunopathogenesis of this disease has been achieved. The antigen responsible for RA is still unknown, however, the high specificity of auto-antibodies directed against citrullinated peptides provides some information on the structure of this antigen probably rich in citrullines residues. RA is a polyfactorial disease that involves hormones, genetic and environmental factors, but also immunological disorders which contribute to chronic synovitis. The mechanisms involved in the pathogenesis of the disease are complex and implicate innate immunity (toll like receptors, cytokines, complement) and adaptative immune response characterised by a T cell-mediated antigen specific response implicating antigen presenting cells, B and T lymphocytes. Immunopathogenesis of RA can be subdivided in three different phases: an early phase involving innate immunity, an established phase characterised by chronic synovitis depending essentially on adaptative immune response, and a destructive phase related to cytokines effect (TNFα, IL-1β, metalloproteinases, RANKL) but also a tumour-like proliferation of fibroblast such as synoviocytes related to apoptosis defect. The better understanding of RA immunopathogenesis has led to the development of specific therapeutic interventions such as biologic agents. Based on the pathogenic mechanisms, novel treatment targeting cytokines, intracellular signalling pathways or lymphocyte co-stimulation proteins.