[Approach from bedside to etiology/pathophysiology/treatment of rheumatoid arthritis].
Rheumatoid arthritis (RA) is a disease full of variety. We need to elucidate various clinical doubts for the complete cure of RA. We observed a lot of patients with human parvovirus B19 (B19) infection who developed to RA till now. We investigated B19 infection in relation with RA etiology. B19 infects persistently to immune cells through cell surface Ku80 autoantigen as a cellular receptor. We are able to detect B19 in immune cells which infiltrate in synovial tissues of patients with RA. B19 is activated in infected cells, and functional viral protein NS1 induces over production of inflammatory cytokine TNFalpha. As a result, it promotes a neutrophile activation and migration to the synovium where there are B19-infected immune cells. This may cause arthritis and create a vicious circle of chronic inflammation that develops into RA. As for the B19 persistent infection to immune cells, abnormality of anti-B19 humoral immunity may participate in imperfection of B19 neutralization of a host. It is expected the development of effective treatment that cure progressing RA from B19 infection. NS1 may be one of the candidates of therapeutic target.
Munakata
Yasuhiko
Y
Department of Rheumatology and Hematology, Tohoku University Graduate School of Medicine.
D000328:Adult; D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000503:physiopathology* / Q000628:therapy; D004279:DNA, Viral / Q000302:isolation & purification*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006367:HeLa Cells; D006801:Humans; D000072200:Ku Autoantigen; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D010322:Parvoviridae Infections / Q000150:complications*; D016732:Parvovirus B19, Human; D019095:Point-of-Care Systems
D034961:Antigens, Nuclear; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen