Clinical correlations with HLA type in Japanese patients with connective tissue disease and anti–U1 small nuclear RNP antibodies

Kuwana, Masataka; Okano, Yutaka; Kaburaki, Junichi; Inoko, Hidetoshi

doi:10.1002/art.1780390610

Cited by 16 publications

(4 citation statements)

References 11 publications

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“…KUWANA ET AL autoantibody specificities in patients with anti-U1 RNP antibody and connective tissue disease (39,40). HLA class II gene associations with anti-topo I antibody in the current study were principally concordant with the findings of previous investigations (41)(42)(43).…”

supporting

confidence: 91%

Influence of ethnic background on clinical and serologic features in patients with systemic sclerosis and anti-DNA topoisomerase I antibody

Kuwana

Kaburaki

Arnett

et al. 1999

Arthritis & Rheumatism

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127

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Objective. To investigate the effect of ethnicity on clinical and serologic expression in patients with systemic sclerosis (SSc) and anti-DNA topoisomerase I (anti-topo I) antibody.Methods. Clinical and serologic features, as well as HLA class II allele frequencies, were compared among 47 North American white, 15 North American black, 43 Japanese, and 12 Choctaw Native American SSc patients with anti-topo I antibody.Results. The frequency of progressive pulmonary interstitial fibrosis was lower, and cumulative survival rates were better in white compared with black and Japanese patients. Sera of white and black patients frequently recognized the portion adjacent to the carboxyl terminus of topo I, sera of Japanese patients preferentially recognized the portion adjacent to the amino terminus of topo I, and sera of Choctaw patients recognized both portions of topo I. Anti-RNA polymerase II and anti-SSA/Ro antibodies were present together with anti-topo I antibody more frequently in sera of Japanese patients than in sera of white patients. The HLA-DRB1 alleles associated with anti-topo I antibody differed; i.e., DRB1*1101-*1104 in whites and blacks, DRB1*1502 in Japanese, and DRB1*1602 in Choctaws.Multivariate analysis showed that ethnic background was an independent determinant affecting development of severe lung disease as well as survival.Conclusion. Clinical and serologic features in SSc patients were strongly influenced by ethnic background. The variability of disease expression in the 4 ethnic groups suggests that multiple factors linked to ethnicity, including genetic and environmental factors, modulate clinical manifestations, disease course, and autoantibody status in SSc.

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supporting

confidence: 91%

Influence of ethnic background on clinical and serologic features in patients with systemic sclerosis and anti-DNA topoisomerase I antibody

Kuwana

Kaburaki

Arnett

et al. 1999

Arthritis & Rheumatism

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127

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“…The presence of autoantibodies is a central feature of SSc, since antinuclear antibodies (Abs) are detected in >90% of patients (2). SSc patients have autoantibodies that react to various intracellular components, such as DNA topoisomerase I (topo I), centromeric protein B (CENP B), U1-ribonucleoprotein (RNP), and histone (2). Furthermore, abnormal activation of immune cells, including T cells, B cells, NK cells, and macrophages, has been identified in SSc (3).…”

Section: Introductionmentioning

confidence: 99%

Cell Adhesion Molecules Regulate Fibrotic Process via Th1/Th2/Th17 Cell Balance in a Bleomycin-Induced Scleroderma Model

Yoshizaki

Yanaba

Iwata

et al. 2010

The Journal of Immunology

126

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Mice subcutaneously injected with bleomycin, an experimental model for human systemic sclerosis, develop skin and lung fibrosis, which is mediated by inflammatory cell infiltration. This process is highly regulated by multiple adhesion molecules. To assess the role of adhesion molecules in this pathogenetic process, the bleomycin-induced fibrosis was examined in mice lacking adhesion molecules. In addition, this model does not require antigen sensitization. Therefore, we can exclude the possible role of adhesion molecules on the sensitization phase. L-selectin and/or ICAM-1 deficiency inhibited skin and lung fibrosis with decreased Th2 and Th17 cytokines and increased Th1 cytokines. By contrast, P-selectin deficiency, E-selectin deficiency with or without P-selectin blockade, or PSGL-1 deficiency augmented the fibrosis in parallel with increased Th2 and Th17 cytokines and decreased Th1 cytokines. Furthermore, loss of L-selectin and/or ICAM-1 reduced Th2 and Th17 cell numbers in bronchoalveolar lavage fluid, whereas loss of P-selectin, E-selectin, or PSGL-1 reduced Th1 cell numbers. Moreover, Th1 cells exhibited higher PSGL-1 expression and lower expression of LFA-1, a ligand for ICAM-1, while Th2 and Th17 cells showed higher LFA-1 and lower PSGL-1 expression. This study suggests that L-selectin and ICAM-1 regulate Th2 and Th17 cell accumulation into the skin and lung, leading to the development of fibrosis, and that P-selectin, E-selectin, and PSGL-1 regulate Th1 cell infiltration, resulting in the inhibition of fibrosis.

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“…Systemic sclerosis (SSc) is a connective tissue disease characterized by excessive extracellular matrix deposition with an autoimmune background (1). The presence of autoantibodies is a central feature of SSc, since antinuclear antibodies (ANAs), such as anti–DNA topoisomerase I (anti–topo I) antibody, are detected in >90% of patients (2). Furthermore, abnormal activation of several immune cells has been identified in SSc (3).…”

mentioning

confidence: 99%

Immunization with DNA topoisomerase I and Freund's complete adjuvant induces skin and lung fibrosis and autoimmunity via interleukin‐6 signaling

Yoshizaki¹,

Yanaba²,

Ogawa³

et al. 2011

Arthritis & Rheumatism

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Objective. The presence of anti-DNA topoisomerase I (anti-topo I) antibody correlates positively with disease severity in patients with systemic sclerosis (SSc). However, the role of induction of anti-topo I antibody production and its potential contribution to the pathogenesis of SSc remain unclear. The aim of this study was to examine the role of anti-topo I antibody in the pathogenesis of SSc.Methods. To assess the contribution of anti-topo I antibody to the pathogenetic process, dermal sclerosis, pulmonary fibrosis, and cytokine production were examined in mice treated with topo I and either Freund's complete adjuvant (CFA) or Freund's incomplete adjuvant (IFA).Results. Treatment with topo I and CFA, in contrast to treatment with topo I and IFA, induced skin and lung fibrosis with increased interleukin-6 (IL-6), transforming growth factor ␤1, and IL-17 production and decreased IL-10 production. Anti-topo I antibody levels were greater in mice treated with topo I and CFA than in mice treated with topo I and IFA. Furthermore, treatment with topo I and CFA increased Th2 and Th17 cell frequencies in bronchoalveolar lavage fluid, whereas treatment with topo I and IFA increased Th1 and Treg cell frequencies. Moreover, loss of IL-6 expression ameliorated skin and lung fibrosis, decreased Th2 and Th17 cell frequencies, and increased Th1 and Treg cell frequencies.Conclusion. This study is the first to show that treatment with topo I and CFA induces SSc-like skin and lung fibrosis and autoimmune abnormalities. We also suggest that IL-6 plays important roles in the development of fibrosis and autoimmune abnormalities in this novel SSc model.

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Clinical correlations with HLA type in Japanese patients with connective tissue disease and anti–U1 small nuclear RNP antibodies

Cited by 16 publications

References 11 publications

Influence of ethnic background on clinical and serologic features in patients with systemic sclerosis and anti-DNA topoisomerase I antibody

Influence of ethnic background on clinical and serologic features in patients with systemic sclerosis and anti-DNA topoisomerase I antibody

Cell Adhesion Molecules Regulate Fibrotic Process via Th1/Th2/Th17 Cell Balance in a Bleomycin-Induced Scleroderma Model

Immunization with DNA topoisomerase I and Freund's complete adjuvant induces skin and lung fibrosis and autoimmunity via interleukin‐6 signaling

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