Rheumatoid arthritis: from autoimmunity to synovitis and joint destruction.
Rheumatoid arthritis is an autoimmune disease characterized by the production of two known antibodies - rheumatoid factor and anti-citrullinated peptide antibody (ACPA) - against common autoantigens that are widely expressed within and outside the joints. The interactions between genes and environment are crucial in all stages of the disease, involving namely genes from major histocompatibility complex locus, and antigens such as tobacco or microbes (e.g. Porphyromonas gingivalis). T and B cells are activated as soon as the earliest phases of the disease, rheumatoid arthritis appearing as a Th1 and Th17 disease. Inflammatory cytokines have a considerable importance in the hierarchy of the processes involved in RA. The joint destruction seen in RA is caused not only by cytokine imbalances, but also by specific effects of the Wnt system and osteoprotegerin on osteoclasts and by matrix production dysregulation responsible for cartilage damage. Both innate and adaptative immunity demonstrated their respective cornerstone position in rheumatoid arthritis, since targeted treatments has been efficiently developed against TNF-α, IL-6 receptor, IL-1β, CD20 B cells and T-cell/Dendritic cell interactions.
Université Sorbonne Paris Cité, Université Paris 13, Li2P, EA4222 Bobigny, France. marie-christophe.boissier@avc.aphp.fr
Marie-Christophe
MC
Boissier
Luca
L
Semerano
Salima
S
Challal
Nathalie
N
Saidenberg-Kermanac'h
Géraldine
G
Falgarone
D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology; D006801:Humans; D007596:Joints / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects / Q000276:immunology; D012217:Rheumatoid Factor / Q000096:biosynthesis / Q000276:immunology; D013585:Synovitis / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology
D018501:Antirheumatic Agents; D001323:Autoantibodies; D016207:Cytokines; D012217:Rheumatoid Factor