[Recent advances in the pathogenesis of rheumatoid arthritis].
Rheumatoid arthritis is a chronic inflammatory polyarthritis and is thought to be an autoimmune, multifactorial and polygenic disease. Recent studies have uncovered many important players in the pathogenesis of rheumatoid arthritis. Immune cells, mesenchymal cells, and bone-associated cells are all involved in the pathogenesis and are closely related with each other. The genetic predisposition to rheumatoid arthritis is confirmed by many family studies and HLA association studies. Genome-wide disease association studies identified genetic risk foci, such as HLA-DRB1, PADI4, and PTPN22. In addition to the genetic contribution, environmental factors are increasingly recognized. Many studies revealed that smoking is a risk factor for rheumatoid arthritis. The role of B and T lymphocytes in the pathogenesis has been reevaluated by biological agents such as rituximab (anti-CD20 antibody) and abatacept (CTLA4-Ig) , respectively. T cells in rheumatoid arthritis have been shown to have the altered level of surface molecules such as CD28, cytokine pattern shift, and shortened telomere lengths. Moreover, telomere loss is recognized not only in lymphocytes but also in hematopoietic progenitor cells. This phenomenon and the presence of rheumatoid-specific anti-citrullinated protein antibodies are reported to be associated with HLA haplotypes.
Kawabata
Kimito
K
Division of Allergy and Rheumatology, Department of Medicine, University of Tokyo Hospital.
Yamamoto
Kazuhiko
K
D000069594:Abatacept; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000628:therapy; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006801:Humans; D006867:Hydrolases; D018796:Immunoconjugates / Q000627:therapeutic use; D008214:Lymphocytes / Q000276:immunology; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D012307:Risk Factors; D000069283:Rituximab; D012907:Smoking / Q000009:adverse effects
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D018796:Immunoconjugates; D000069283:Rituximab; D000069594:Abatacept; D006867:Hydrolases; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases