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To investigate the role of human parvovirus B19 infection in the pathogenesis of rheumatoid arthritis (RA) in Taiwan.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.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(-).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.

Systemic lupus erythematosus (SLE) is a severe autoimmune disease with rare remission and recurrent flare. Epstein-Barr virus (EBV) infection has been reported to be strongly associated with SLE in the United States, but with an inconclusive role in Asia. We investigated the role of EBV infection in patients with SLE in Taiwan, with one of the highest population densities in Asia.We conducted case-control studies to test whether EBV infection was associated with adult SLE in Taiwan. In the first study, 36 adults with SLE and 36 sex and age matched controls were enrolled for examination of serum IgG, IgM, and IgA antibody against EBV-virus capsid antigen (EBV-VCA). In the second study, another 36 adult lupus cases and 36 matched controls were enrolled to confirm the high prevalence of IgA antibody against EBV-VCA found in the first study. Further, both groups of SLE patients were combined to analyze the association between the existence of IgA antibody against EBV-VCA and disease activity (determined by SLEDAI score) and disease flare in patients with SLE.In the first study, IgA antibody against EBV-VCA was the only marker with significantly higher prevalence in adults with SLE compared to healthy adults (36.1% vs 5.6%; p0.005). In the second study, we confirmed that the prevalence of IgA antibody against EBV-VCA was indeed higher in adults with SLE (38.9% vs 2.8%; p0.001). With further analysis (pooling analysis), adult SLE patients with IgA antibody against EBV-VCA had higher disease activity compared to SLE patients without IgA antibody against EBV-VCA (SLEDAI 7.8 +/- 6.6 vs 3.3 +/- 2.1; p0.001). SLE patients with flare showed much higher prevalence of IgA antibody against EBV-VCA compared to those without flare (81.3% vs 25.0%; p0.001).This is the first evidence that IgA antibody against EBV-VCA is strongly associated with disease flare in SLE patients. It suggests that EBV reactivation may contribute toward the disease flare of SLE.

To investigate the association of cytochrome p450 1A1 (CYP1A1) and manganese superoxide dismutase (MnSOD) gene polymorphisms with susceptibility to Behçet's disease (BD) in Taiwan.The polymorphisms of CYP1A1 and MnSOD genes were determined in 51 patients with BD and 91 healthy controls by polymerase chain reaction/restriction fragment length polymorphism methods.The frequencies of CYP1A1 4889G and 4887A were significantly increased in patients with BD. In contrast, there was no significant difference in the frequencies of MnSOD gene polymorphisms between patients with BD and controls. Linkage disequilibrium was found between CYP1A1 4889G and CYP1A1 6235C in controls and patients with BD. However, a similar finding could not be found between CYP1A1 4889G and 4887A. We also found that the association of CYP1A1 4889G with BD was dependent on the presence of CYP1A1 4887A. On the other hand, the association of CYP1A1 4887A with BD was dependent on the presence of CYP1A1 4889G. An additive effect of CYP1A1 4889G and 4887A on the susceptibility to BD could be found.Simultaneous presence of CYP1A1 4889G and 4887A is associated with development of BD in Taiwan.

To investigate the role of tumor necrosis factor receptor 2 microsatellite allele (TNFR2ms) and TNFR2 exon 6 polymorphisms in the pathogenesis of rheumatoid arthritis (RA) in Taiwan. Methods. TNFR2ms was determined in 114 patients with RA and 75 healthy controls by polymerase chain reaction (PCR) method and electrophoresis with sequencing gel. The TNFR2 exon 6 polymorphisms were also simultaneously measured by PCR restriction fragment length polymorphism method.The phenotypic and allelic frequencies of TNFR2ms 18 were significantly lower in patients with RA than in controls. The genotype frequency of TNFR2ms 16/18 was also significantly decreased in patients. In contrast, the phenotypic and allelic frequencies of TNFR2ms 15 showed a trend to be increased in patients with RA. There were no significant differences in the frequencies of various TNFR2ms and exon 6 polymorphisms concerning presence and absence of rheumatoid factor, bone erosion, rheumatoid nodules, or Sjögren's syndrome manifestation. Conclusion. TNFR2ms 18 may have a protective effect on the development of RA in Taiwanese, while TNFR2ms 15 tends to have a precipitating effect. TNFR2 exon 6 polymorphisms are not related to susceptibility for RA. TNFR2ms and exon 6 polymorphisms were not associated with the clinical manifestations of RA in Taiwanese. A synergistic effect for susceptibility to RA was found between TNFR2ms 15 and HLA-DR4.

A fully complexed HLA-B27 molecule consists of a heavy chain, a peptide, and beta2-microglobulin (beta2m). The heavy chain can also exist free of beta2m. It has been proposed from animal and in vitro experiments that the free heavy chain is responsible for disease. We wanted to determine the following for patients with ankylosing spondylitis (AS): (1) are there cells expressing cell surface free heavy chains; (2) if so, which subset of cells has such capacity; (3) does expression vary with disease activity; (4) can we find free heavy chain-expressing cells at the site of inflammation that is characteristic of the disease; and (5) can such expression be induced in healthy subjects.Quantitative flow cytometry was carried out using antibodies directed separately against HLA class I complex, free heavy chain A or B alleles. Antibodies directed against other cell surface markers were used to identify cell types. Immunohistochemical staining was used to stain synovial tissue.There was a high level of surface expression of free heavy chains in monocytes of patients with AS. The level exceeded those of normal controls and patients with rheumatoid arthritis. The level of expression correlated with the inflammation marker, erythrocyte sedimentation rate. The level of expression was enhanced when monocytes from healthy controls were driven to differentiation by longterm culture. Free heavy chain-expressing monocytes infiltrated the synovium of an involved hip joint of a patient with AS.This is the first patient-related evidence that surface free heavy chains of HLA-B27 have to be considered as potential disease-causing molecules.