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OBJECTIVE: To investigate the role of human parvovirus B19 infection in the pathogenesis of rheumatoid arthritis (RA) in Taiwan. METHODS: Seventy-eight patients with RA and 55 unrelated controls (51 trauma and 4 osteoarthritis) were enrolled. Anti-parvovirus B19 IgG and IgM antibodies were detected in plasma of patients with RA and controls by the enzyme immunoassay method. These antibodies were also detected in the synovial fluid of 18 RA patients and 52 controls. B19 DNA was measured in the plasma of 72 patients with RA and 45 controls by nested polymerase chain reaction (PCR). It was also measured in the synovial fluid of 14 RA patients and 39 controls. Immunohistochemistry was performed to detect viral capsid protein VP1 of B19 in the synovial membrane of 7 RA patients and 32 controls. HLA-DR genotyping was performed by the sequence-specific primer PCR method. The interactions between B19 infection and HLA-DR genotype and susceptibility to RA were also analyzed. RESULTS: The prevalence of B19 infection was significantly increased in patients with RA compared with controls. The positive rates of B19 DNA in plasma and synovial fluid were significantly higher in RA patients than in controls. The odds ratio of DR4(+) B19 infection(+) was higher than that in DR4(+) B19 infection(-) or DR4(-) B19 infection(+) in comparison with DR4(-) B19 infection(-). A significant association was found between RA and DR4(+) B19 infection(+) in comparison with DR4(+) B19 infection(-). The odds ratio of DR4(+) plasma B19 DNA(+) was also higher than that of DR4(+) plasma B19 DNA(-) or DR4(-) plasma B19 DNA(+) in comparison with DR4(-) plasma B19 DNA(-). RA tended to be associated with DR4(+) plasma B19 DNA(+) compared with DR4(+) plasma B19 DNA(-). CONCLUSION: The prevalence of parvovirus B19 infection was significantly higher in patients with RA than in controls. Synergistic effects were present between HLA-DR4 and parvovirus B19 infection or plasma B19 DNA for susceptibility to RA. Parvovirus B19 infection may play a role in susceptibility to RA.