Rheumatoid Arthritis: Tsai WC

Ou TT, Lin CH, Lin YC, Li RN, Tsai WC, Liu HW, Yen JH. · Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Zihyou 1st Road, Kaohsiung City 807, Taiwan. · J Clin Immunol. · Pubmed #18600435 No free full text.

Abstract: INTRODUCTION: To investigate the association of IkBalpha promoter polymorphisms with the development of primary Sjögren's syndrome in Taiwan, 98 patients with primary Sjögren's syndrome and 110 unrelated healthy controls were enrolled in this study. MATERIALS AND METHODS: The IkappaBalpha -881 A/G, IkappaBalpha -826 C/T, IkappaBalpha -550 A/T, IkappaBalpha -519 C/T, and IkappaBalpha -297 C/T polymorphisms were determined by the methods of polymerase chain reaction/restriction fragment length polymorphism. RESULTS: This study demonstrated that the genotype frequencies of IkappaBalpha -826 C/T and IkappaBalpha -826 T/T, in comparison with that of IkappaBalpha -826 C/C, were significantly higher in the patients with primary Sjögren's syndrome than in the controls. The allele frequency of IkappaBalpha -881 G was significantly decreased in the patients with primary Sjögren's syndrome compared with that of the controls. In contrast, the allele frequency of IkappaBalpha -826 T was significantly higher in the patients with primary Sjögren's syndrome than in the controls. The similar findings could also be found in the allele carriage frequencies. The patients with primary Sjögren's syndrome had lower allele carriage frequencies of IkappaBalpha -881 G and IkappaBalpha -826 C, and a higher allele carriage frequency of IkappaBalpha -826 T. We also found that the estimated haplotype frequency of IkappaBalpha -881A-826T-550A-519C-297C was significantly increased in the patients with primary Sjögren's syndrome in comparison with that of the controls. DISCUSSION: This study demonstrated that the IkBalpha -826T allele and IkBalpha -881A-826T-550A-519C-297C haplotype were associated with susceptibility to primary Sjögren's syndrome in Taiwan. However, these findings may not be disease-specific but may be related to inflammatory responses.

Wang SC, Lin CH, Li RN, Ou TT, Wu CC, Tsai WC, Liu HW, Yen JH. · Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · J Clin Immunol. · Pubmed #17597384 No free full text.

Abstract: To investigate the role of ligands for programmed cell death 1 (PD-L) in the pathogenesis of rheumatoid arthritis (RA), 129 patients with RA and 125 unrelated healthy controls were enrolled in this study. The PD-L1 and PD-L2 polymorphisms were determined by the method of polymerase chain reaction (PCR)/direct sequencing or PCR/reaction fragment length polymorphisms. The genotype distributions of PD-L1 6777 C/G were not significantly different between the patients with RA and healthy controls. There was also no significant difference in the allele frequencies of PD-L1 6777 C/G polymorphisms between the patients with RA and controls. Similar findings could also be found in the phenotypes and alleles frequencies of PD-L2 47103 C/T and 47139 T/C polymorphisms between the patients with RA and controls. The patients with PD-L1 6777 G had higher prevalence of rheumatoid nodule in comparison with those without PD-L1 6777 G (p = 0.005, OR = 4.0, 95% CI = 1.5-10.9). In contrast, the PD-L2 47103 C/T and 47139 T/C polymorphisms were not related to the occurrence of rheumatoid nodule. This study demonstrated that the PD-L1 and PD-L2 polymorphisms were not associated with susceptibility to RA in Taiwan. PD-L1 6777 G was associated with the prevalence of rheumatoid nodule.

Lin CH, Ou TT, Wu CC, Tsai WC, Liu HW, Yen JH. · Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan. · Int J Immunogenet. · Pubmed #17284228 No free full text.

Abstract: To investigate the role of inhibitor of kappaBalpha promoter polymorphisms in the pathogenesis of rheumatoid arthritis (RA), 140 patients with RA and 115 healthy controls were enrolled in this study. The IkappaBalpha promoter polymorphisms were determined using the polymerase chain reaction/restriction fragment length polymorphisms method. In comparison with IkappaBalpha-826 C/C, the genotype frequency of IkappaBalpha-826 C/T was significantly higher in the patients with RA than that of the controls (P = 0.009, OR = 2.0, 95% CI = 1.2-3.4). The allele frequency of IkappaBalpha-826 T was also significantly increased in patients with RA when compared with that of the controls (P = 0.027, OR = 1.6, 95% CI = 1.1-2.4). In comparison with IkappaBalpha-550 A/A, the genotype frequency of IkappaBalpha-550 A/T was significantly decreased in patients with RA when compared with that of the controls (P = 0.02, OR = 0.2, 95% CI = 0.06-0.8). The allele frequency of IkappaBalpha-550 A was significantly increased in patients with RA (P = 0.007, OR = 5.1, 95% = 1.4-18.2). This study also revealed that the IkappaBalpha-826 T -550 A -519 C haplotype was significantly increased in patients with RA in comparison to that of controls (P = 0.01, OR = 1.8, 95% CI = 1.1-2.8). The IkappaBalpha-826 T and -550 A alleles are associated with susceptibility to RA. Moreover, the IkappaBalpha-826 T -550 A -519 C haplotype is associated with susceptibility to RA in Taiwan.

Lin CH, Cho CL, Tsai WC, Ou TT, Wu CC, Yen JH, Liu HW. · Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Taiwan. · Immunol Lett. · Pubmed #16644022 No free full text.

Abstract: OBJECTIVES: To investigate the role of inhibitor of kB-like (IkBL) gene polymorphisms in the pathogenesis of rheumatoid arthritis (RA) in Taiwan. METHODS: One hundred and twenty-nine patients with RA and 110 healthy controls were enrolled in this study. Polymerase chain reaction (PCR)/direct sequencing was used to determine the polymorphisms of IkBL -421 8T/9T, -324 C/G, -262 A/G, and -62 A/T. PCR/restriction fragment length polymorphism was used to determine the IkBL +738 T/C polymorphisms. RESULTS: The genotype distribution of IkBL -421 was significantly different between DR4(+) RA patients and DR4(+) controls (p = 0.02). The allele frequency of IkBL -421 8T was significantly higher in DR4(+) RA patients than in DR4(+) controls (p = 0.004, OR = 7.2, 95% CI = 1.7-29.2). The allele carriage frequency of IkBL -421 8T also tended to be increased in DR4(+) RA patients in comparison with DR4(+) controls (p = 0.07, OR = 14.6, 95% CI = 1.4-147.0). We also found that the allele frequency of IkBL -62 T was significantly higher in RA patients than in controls (p = 0.04, OR = 1.5, 95% CI = 1.1-2.1). The allele carriage frequency of IkBL -62 T tended to be increased in RA patients (p = 0.08, OR = 1.7, 95% CI = 1.0-3.0). The estimated haplotype frequency of IkBL -421 8T/-62 T tended to be increased in RA patients compared with controls (p = 0.07, OR = 1.4, 95% CI = 1.0-2.0). CONCLUSION: The IkBL -62 T may be associated with the development of RA in Taiwan. The IkBL -421 8T may also be related to susceptibility to RA in HLA-DR4(+) individuals. This study shows that the estimated haplotype IkBL -421 8T/-62 T tends to be associated with susceptibility to RA in Taiwan.

Yen JH, Lin CH, Tsai WC, Wu CC, Ou TT, Hu CJ, Liu HW. · Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. · Scand J Rheumatol. · Pubmed #16641046 No free full text.

Abstract: OBJECTIVE: To investigate the role of the killer cell immunoglobulin-like receptor (KIR) gene's repertoire in the pathogenesis of rheumatoid arthritis (RA) in Taiwan. METHODS: KIR genotypes were determined in 122 patients with RA and 96 healthy controls by the sequence-specific primer polymerase chain reaction (SSP-PCR) method. Human leucocyte antigen (HLA)-C genotyping was also performed simultaneously in 72 patients and 66 controls by the SSP-PCR method. RESULTS: The total carriage frequency of KIR 2DS4 regardless of corresponding HLA-Cw4 was significantly increased in RA patients compared with controls [p<0.001, odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1-3.4, Pc<0.01]. The total carriage frequency of KIR 2DL1 regardless of corresponding HLA-C also tended to be increased in RA patients (p<0.02, OR = 2.1, 95% CI = 1.2-3.9, Pc = not significant). The frequency of KIR 2DS4 with corresponding HLA-Cw4 was increased in RA patients in comparison with controls (p = 0.02, OR = 3.2, 95% CI = 1.1-9.4). Moreover, the association of RA with KIR 2DS4 depended on the presence of the corresponding HLA-Cw4. CONCLUSIONS: KIR 2DS4 may be a risk factor for susceptibility to RA in Taiwan.

Chen YS, Chou PH, Li SN, Tsai WC, Lin KH, Tsai KB, Yen JH, Liu HW. · No affiliation provided · J Rheumatol. · Pubmed #16511938 No free full text.

Abstract: 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.

Yen JH, Lin CH, Tsai WC, Ou TT, Wu CC, Hu CJ, Liu HW. · Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, No. 100 Zihyou First Road, Kaohsiung 807, Taiwan. · Immunol Lett. · Pubmed #16125248 No free full text.

Abstract: OBJECTIVES: To investigate the association of natural resistance-associated macrophage protein 1 gene (NRAMP1) polymorphisms with rheumatoid arthritis (RA) in Taiwan. METHODS: NRAMP1 polymorphisms were determined from 113 RA patients and 74 healthy controls using the polymerase chain reaction/restriction fragment length polymorphism method. RESULTS: The genotype frequencies of NRAMP1 823 C/C, 1703G/G (543D/D), and 1729+55 del 4 TGTG+/+ (244/244) were significantly higher in patients with RA than in controls. Similar findings were also evident in allele frequencies and allele carriage frequencies of 823C, 1703G (543D), and 1729+55 del 4 TGTG+ (244). The associations of these polymorphisms with RA were independent of HLA-DR4. Linkage disequilibria could be found between 823C and 1703G, and between 1703G and 1729+55 del 4 TGTG+. The estimated haplotype frequency of NRAMP1 823C/1703G/1729+55 del 4 TGTG+ was significantly increased in RA patients compared with controls. We also found that patients with 823 C/C had a significantly lower prevalence of rheumatoid nodule than those without 823 C/C. CONCLUSION: NRAMP1 823C, 1703G (543D), and 1729+55 del 4 TGTG+ (244) are precipitating factors for the development of RA in Taiwan. The estimated NRAMP1 823C/1703G/1729+del 4 TGTG+ haplotype is associated with susceptibility to RA. NRAMP1 823 C/C prevents the development of rheumatoid nodule in RA patients.

Wu CC, Yu HC, Yen JH, Tsai WC, Liu HW. · Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · Kaohsiung J Med Sci. · Pubmed #15960070 links to  free full text

Abstract: Rheumatoid arthritis is a systemic disease with manifestations in many organs. In most cases, involvement of the locomotor system dominates the clinical picture. However, extra-articular manifestations can be detected in almost any organ system with varied incidence in different series. Ophthalmic presentations include Sjogren's syndrome, episcleritis, and scleritis. The most severe form of scleritis, scleromalacia perforans, is a very rare ophthalmic manifestation. We present the case of a 60-year-old man who had had rheumatoid arthritis for more than 10 years. He had scleromalacia perforans but no other extra-articular manifestations.

Lin SC, Yen JH, Tsai JJ, Tsai WC, Ou TT, Liu HW, Chen CJ. · Cathay General Hospital, Taipei, Taiwan. · Arthritis Rheum. · Pubmed #15022318 links to  free full text

Abstract: OBJECTIVE: The expression of autoimmunity in mice deficient in programmed death 1 (PD-1) suggests that PD-1 is a candidate gene involved in the development of human autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We therefore tested the potential association between PD-1 and the development of SLE and RA by conducting case-control genetic-association studies. METHODS: Ninety-eight SLE patients, 84 RA patients, and sex-matched control subjects for each disease group were recruited and genotyped for a single-nucleotide polymorphism, C+872T, in the human PD-1 gene. The significance of the association of the PD-1 gene with SLE or with RA was analyzed by statistical tests for the difference in genotype distribution between disease and control groups. RESULTS: The human PD-1 gene was found to be significantly associated with disease development in RA patients, but not SLE patients. The risk of RA development appeared to be significantly increased by carriage of the T allele (odds ratio 3.32, P < 0.0001) or the C/T genotype (odds ratio 3.52, P < 0.00005). CONCLUSION: The PD-1 gene is significantly associated with RA susceptibility, suggesting the possibility that PD-1 may contribute to the pathogenesis of RA.

Yen JH, Tsai WC, Chen CJ, Ou TT, Lin CH, Hu CJ, Liu HW. · Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan. · J Rheumatol. · Pubmed #12610797 No free full text.

Abstract: OBJECTIVE: 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. RESULTS: 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.

Yen JH, Chen CJ, Tsai WC, Lin CH, Ou TT, Hu CJ, Liu HW. · Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan. · Hum Immunol. · Pubmed #12590982 No free full text.

Abstract: To investigate the role of manganese superoxide dismutase (MnSOD) and cytochrome P450 1A1 (CYP1A1) gene polymorphisms in the pathogenesis of rheumatoid arthritis (RA) in Taiwan, MnSOD and CYP1A1 genes polymorphisms were determined by he polymerase chain reaction/restriction fragment length polymorphism method in 112 patients with RA and 96 controls. There were no significant differences in the genotype, allele, and phenotype frequencies of MnSOD Ala-9Val (C1183T) polymorphisms between patients with RA and controls. The polymorphism of MnSOD 5777T, threonine at the 58th amino acid, cannot be found in RA patients and controls in Taiwan. The allele and phenotype frequencies of CYP1A1 4887A and genotype frequency of CYP1A1 4887C/A were lower in RA patients than in controls, whereas the significant difference was lost after correction. MnSOD C1183T polymorphisms were not associated with the clinical manifestations of RA. However, RA patients with CYP1A1 4889G/G have significantly higher frequency of Sjögren's syndrome, especially in the presence of MnSOD 1183T/T. Patients with CYP1A1 4887C/A also have a trend to develop Sjögren's syndrome in the presence of MnSOD 1183T/T. The linkage disequilibrium between CYP1A1 4889G and CYP1A1 6235C can be found in this study. MnSOD gene polymorphisms are not related to susceptibility to RA in Taiwan, whereas individuals with CYP1A1 4887A tend to avoid the development of RA. Moreover, CYP1A1 4889G/G and 4887C/A may play a role in the development of Sjögren's syndrome, especially in the presence of MnSOD 1183T/T. These findings are preliminary. A further confirmation study is necessary.

Gu J, Rihl M, Märker-Hermann E, Baeten D, Kuipers JG, Song YW, Maksymowych WP, Burgos-Vargas R, Veys EM, De Keyser F, Deister H, Xiong M, Huang F, Tsai WC, Yu DT. · University of California Los Angeles, 90095, USA. · J Rheumatol. · Pubmed #12375327 No free full text.

Abstract: OBJECTIVE: To use gene expression profiles of spondyloarthropathy (SpA) synovial fluid mononuclear cells (SFMC) to determine if there are transcripts that support the unfolded protein response (UPR) hypothesis, and to identify which cytokines/chemokines are being expressed and which cell fractions are involved. METHODS: Gene expression profiles were generated by microarray screening of SFMC of 5 patients with SpA, 5 patients with rheumatoid arthritis (RA), and peripheral blood mononuclear cells (PBMC) of 6 controls. Results were validated by reverse transcription polymerase chain reaction using samples from a larger panel of subjects. RESULTS: The repertoires of proinflammatory cytokines/chemokines expressed by SpA and RA SFMC were very similar: monocyte chemotractant protein 1 (MCP-1), interleukin 8 (IL-8), IL-1beta, endothelial-monocyte activating polypeptide II, interferon-gamma, and tumor necrosis factor-alpha. MCP-1 was highly expressed in SpA SFMC. There was enhanced expression of immunoglobulin heavy chain binding protein (BiP) in SpA, which is compatible with the UPR hypothesis. BiP was most highly expressed in the adherent fraction of SpA SFMC. CONCLUSION: Previous data postulating UPR in SpA are based on in vitro experiments with transfected cell lines. Our patient derived data suggest that it also occurs in vivo in the macrophages of SpA joints.

Gu J, Märker-Hermann E, Baeten D, Tsai WC, Gladman D, Xiong M, Deister H, Kuipers JG, Huang F, Song YW, Maksymowych W, Kalsi J, Bannai M, Seta N, Rihl M, Crofford LJ, Veys E, De Keyser F, Yu DT. · University of California at Los Angeles, CA 90095, USA. · Rheumatology (Oxford). · Pubmed #12096225 links to  free full text

Abstract: OBJECTIVES: To identify genes which are more highly expressed in the peripheral blood mononuclear cells (PBMC) of patients with spondyloarthropathy (SpA), rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in comparison to normal subjects. METHODS: A 588-gene microarray was used as a screening tool to select a panel of such genes from PBMC of these subjects and of normal subjects. Results were then validated by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The following genes were more highly expressed in arthritis patients than in normal subjects: macrophage differentiation marker MNDA (myeloid nuclear differentiation antigen), MRP8 and MRP14 (migratory inhibitory factor-related proteins); signalling molecules JAK3 (janus kinase 3) and MAP kinase p38 (mitogen-activated protein kinase); receptors TNFR2/p75, C-C-chemokine receptor type 1 (CCR1), C-X-C-chemokine receptor type 4 (CXCR4) and integrin beta1; and the cytokines/chemokines interleukin (IL) 1beta and IL-8. Expression of CXCR4 was unexpectedly high among all arthritis subjects. Using RT-PCR, ELISA and immunohistology, expression of stromal cell-derived factor 1 (SDF-1) was demonstrated in arthritis joints. CONCLUSIONS: The CXCR4/SDF-1 is a potential pro-inflammatory axis for RA, PsA and SpA.

Tsai WC, Chen CJ, Yen JH, Ou TT, Tsai JJ, Liu CS, Liu HW. · Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan. · J Rheumatol. · Pubmed #12022359 No free full text.

Abstract: OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: This is the first patient-related evidence that surface free heavy chains of HLA-B27 have to be considered as potential disease-causing molecules.

Yen JH, Chen CJ, Tsai WC, Lin CH, Ou TT, Lin SC, Dai ZK, Liu HW. · Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100 Shih-Chuan, 1st Road, Kaohsiung807, Taiwan. · Immunol Lett. · Pubmed #11947922 No free full text.

Abstract: OBJECTIVE: To investigate the association of tumor necrosis factor (TNF) microsatellite alleles with the pathogenesis of rheumatoid arthritis (RA) in Taiwan. METHODS: The TNF a, b, c, d, and e microsatellites were determined in 112 patients with RA and 99 healthy controls by using polymerase chain reaction (PCR) and electrophoresis with sequencing gel. All of these patients and controls had known HLA-DR genotypes and TNF-308 polymorphisms. RESULTS: The phenotypic frequency of TNFa9 was significantly higher in DR4(-) RA patients than in DR4(-) controls. However, the phenotypic frequency of TNFb6 was significantly higher in RA patients than in controls in the presence of HLA-DR4. The phenotypic frequency of TNFa3-e1 was significantly lower in DR4(+) RA patients than in DR4(+) controls, while a negative linkage disequilibrium was noted between TNFa3-e1 and HLA-DR4. TNF microsatellite alleles were not related to the prevalences of bone erosion, rheumatoid nodule, sicca syndrome, pulmonary fibrosis, and seropositivity of rheumatoid factor (RF) in patients with RA. CONCLUSION: The associations of TNF microsatellites with the susceptibility to RA in Taiwan are not completely independent of the HLA-DR associations. The association of TNFb6 with the susceptibility to RA depends on the presence of HLA-DR4, and the correlation of TNFa9 to RA depends on the absence of HLA-DR4. The negative association of TNFa3-e1 with RA may be secondary to the negative linkage disequilibrium between TNFa3-e1 and HLA-DR4. Moreover, TNFb6 and HLA-DR4 have a synergistic effect on the susceptibility to RA. TNFa3-e1 and TNF-308A have a synergistic effect on preventing from RA. The TNF microsatellite alleles are not related to the clinical manifestations and severity of RA patients in Taiwan.

Yen JH, Chen CJ, Tsai WC, Lin CH, Ou TT, Wu CC, Liu HW. · Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan, ROC. · J Rheumatol. · Pubmed #11508580 No free full text.

Abstract: OBJECTIVE: To investigate the association of tumor necrosis factor (TNF) promoter polymorphisms with rheumatoid arthritis (RA) in Taiwan. METHODS: TNF promoter polymorphisms at positions -238, -244, -308, -376, -857, and -863 were determined in 97 patients with RA and 97 healthy controls using the PCR-RFLP method. RESULTS: The phenotypic frequency of TNF-308A was significantly lower in patients with RA than in healthy controls. This finding can only be found in HLA-DR4 negative patients, not in DR4 positive RA patients and controls. The TNF promoter polymorphisms at positions -238, -244, -308, -376, -857, and -863 were not related to the clinical manifestations of RA patients. CONCLUSION: TNF-308A itself or a neighboring gene may be a protective factor for the development of RA in the HLA-DR4 negative population in Taiwan. TNF promoter polymorphisms were not associated with the clinical manifestations of patients with RA in Taiwan.

Yen JH, Chen CJ, Tsai WC, Ou TT, Lin CH, Lin SC, Liu HW. · Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Shih-Chuan 1st Road, Kaohsiung City 807, Taiwan. · Kaohsiung J Med Sci. · Pubmed #11482129 No free full text.

Abstract: To investigate the role of HLA-DQA1 genotypes and their interaction with HLA-DRB1 in the pathogenesis of rheumatoid arthritis (RA) in Taiwan, HLA-DQA1 was determined in 71 patients with RA and 108 healthy controls by SSP-PCR method. HLA-DRB1 and HLA-DQA1 were simultaneously detected in 55 RA patients and 101 healthy controls. PCR/SSOP method was used to determine the HLA-DRB1 genotypes, and the subtypes of HLA-DR4 were determined by cloning and sequencing. The phenotypic frequency of HLA-DQA1*0301 was significantly lower in RA than in controls, and, in contrast, the HLA-DQA1*0302 and DQA1*0303 were significantly higher in RA than in controls. The associations of DQA1*0301, *0302, and *0303 with RA were independent of DR4 and DRB1*0405. Moreover, the interactions between HLA-DR4 and HLA-DQA1*0302 or DQA1*0303 could enhance the development of RA. We also found that the prevalence of bone erosion and seropositivity of rheumatoid factor (RF) were significantly higher in HLA-DQA1*0303 positive RA patients than in healthy controls. HLA-DQA1*0302 and DQA1*0303 are the risk factors for susceptibility to RA, while HLA-DQA1*0301 is a protective factor. A synergistic effect for the susceptibility to RA can be found between HLA-DR4 and HLA-DQA1*0302 or DQA1*0303. We also found that the HLA-DQA1*0303 was related to bone erosion and seropositivity of RF in RA patients.

Yen JH, Tsai WC, Tsai JJ, Chen CJ, Lin CH, Ou TT, Wu CC, Liu HW. · Department of Internal Medicine, Kaohsiung Medical College, Taiwan, Republic of China. · Kaohsiung J Med Sci. · Pubmed #10375868 No free full text.

Abstract: To investigate the correlation of HLA-DMA and DMB alleles to some rheumatic diseases, HLA-DMA and DMB genes were detected in 11 patients with juvenile rheumatoid arthritis (JRA), 22 patients with psoriatic arthritis, 26 patients with Behcet's disease, 62 patients with ankylosing spondylitis (AS), and 138 unrelated healthy controls. There was no significant difference in phenotypic frequencies of HLA-DMA and DMB alleles between controls and patients with these rheumatic diseases. HLA-DMA and DMB genes are not related to the susceptibility of JRA, psoriatic arthritis, Behcet's disease, and AS.