The pathogenesis and etiology of systemic sclerosis (SSc) remain unknown, but the presence of several autoantibodies is recognized as one of its prominent features. The clinical significance of anti- DNA topoisomerase...The pathogenesis and etiology of systemic sclerosis (SSc) remain unknown, but the presence of several autoantibodies is recognized as one of its prominent features. The clinical significance of anti- DNA topoisomerase Ⅱ α antibody (anti- topo Ⅱ α Ab) remains unknown in Japanese patients with SSc. To determine the prevalence and clinical correlation of anti- topo Ⅱ α Ab in Japanese patients with SSc. Serum samples were obtained from 103 Japanese patients with SSc. Control serum samples were obtained from 43 healthy Japanese volunteers. Anti- topo Ⅱ α Abs were determined by enzyme linked- immunosorbent assay.IgG anti- topo Ⅱ α Ab levels were significantly increased in SSc patients (n=103) compared to normal controls (n=43; P<0.005). IgG or IgM anti- topo Ⅱ α Ab was detected in 19% (20/103) of SSc patients when absorbance values higher than the mean+ 2SD of control serum samples were considered positive. By contrast, IgG or IgM anti- topo Ⅱ α Ab was observed in only 7% (3/43) of healthy individuals. The presence of pulmonary fibrosis was more frequently detected in SSc patients with IgG anti- topo Ⅱ α Ab than those without the Ab (P<0.05). Moreover, % DLco and % VC were significantly decreased in SSc patients with anti- topo Ⅱ α Ab relative to those without the Ab (P<0.05 and P<0.01, respectively). The elevated levels of both erythrocyte sedimentation rate and C- reactive protein were also more frequently observed in SSc patients positive for IgG anti- topo Ⅱ α Ab (P<0.005). The results of the present study indicate that anti- topo Ⅱ α Ab represent one of the autoantibody specificities detected on SSc patients and may be regarded a serological marker of pulmonary fibrosis in Japanese patients with SSc.展开更多
Natural killer (NK) cells are innate immune effectors that produce various immunoregulatory cytokines. Recent studies have shown that NK cells are involved in the initiation of autoimmunity. In this study, we determin...Natural killer (NK) cells are innate immune effectors that produce various immunoregulatory cytokines. Recent studies have shown that NK cells are involved in the initiation of autoimmunity. In this study, we determined abnormalities of NK cells in systemic sclerosis (SSc), an autoimmune connective tissue disease, by assessing the frequency and absolute number, activation marker expression, cytokine production, and killing activity. The frequency and absolute number of NK cells increased in diffuse cutaneous SSc (dcSSc), whereas they were normal in limited cutaneous SSc (IcSSc). NK cells from both dcSSc and IcSSc patients exhibited activated phenotypes characterized by up-regulated CD16 and CD69 expression and downregulated CD62L expression. Interferon (IFN)-γ production by non-stimulated NK cells from both dcSSc and IcSSc patientswas increased compared to the normal control, whereas on stimulation, a reduced amount of IFN-γ was produced. Interleukin (IL)- 5 and IL- 10 production by non- stimulated NK cells and IL- 6 production by stimulated NK cells were augmented in dcSSc patients, but not in IcSSc patients. Despite the augmented cytokine production by non-stimulated NK cells, natural cytotoxicity activity and granzyme B secretion was reduced in NK cells from dcSSc and IcSSc patients. These results suggested that altered NK cell function contributes to immunological abnormalities in SSc.展开更多
Background: The transforming growth factor-β(TGF-β) system plays a critical role both in systemic sclerosis (SSc) and hereditary hemorrhagic telangiectasia (HHT). Endoglin, known as a gene responsible for HHT, is a ...Background: The transforming growth factor-β(TGF-β) system plays a critical role both in systemic sclerosis (SSc) and hereditary hemorrhagic telangiectasia (HHT). Endoglin, known as a gene responsible for HHT, is a TGF-βreceptor preferentially expressed on endothelial cells. The role of endoglin in SSc is potentially intriguing since limited cutaneous SSc (IcSSc)-and HHT share several symptoms, including telangiectasia. Objective: To determine serum levels of soluble endoglin (sEndoglin) and clinical associations in patients with SSc. Methods: Serums Endoglin levels were examined by ELISA in 70 patients with SSc, 20 patients with systemic lupus erythematosus and 20 healthy individuals. Results: Serum sEndoglin levels were significantly elevated in patients with IcSSc compared with diffuse cutaneous SSc and systemic lupus erythematosus patients as well as normal controls. Patients with elevated sEndoglin levels had telangiectasia more frequently than those with normal sEndoglin levels. Furthermore, pulmonary artery pressure was positively correlated with sEndoglin levels in patients with IcSSc. Conclusion: Abnormal expression/function of endoglin may be linked to IcSSc-specific manifestations.展开更多
文摘The pathogenesis and etiology of systemic sclerosis (SSc) remain unknown, but the presence of several autoantibodies is recognized as one of its prominent features. The clinical significance of anti- DNA topoisomerase Ⅱ α antibody (anti- topo Ⅱ α Ab) remains unknown in Japanese patients with SSc. To determine the prevalence and clinical correlation of anti- topo Ⅱ α Ab in Japanese patients with SSc. Serum samples were obtained from 103 Japanese patients with SSc. Control serum samples were obtained from 43 healthy Japanese volunteers. Anti- topo Ⅱ α Abs were determined by enzyme linked- immunosorbent assay.IgG anti- topo Ⅱ α Ab levels were significantly increased in SSc patients (n=103) compared to normal controls (n=43; P<0.005). IgG or IgM anti- topo Ⅱ α Ab was detected in 19% (20/103) of SSc patients when absorbance values higher than the mean+ 2SD of control serum samples were considered positive. By contrast, IgG or IgM anti- topo Ⅱ α Ab was observed in only 7% (3/43) of healthy individuals. The presence of pulmonary fibrosis was more frequently detected in SSc patients with IgG anti- topo Ⅱ α Ab than those without the Ab (P<0.05). Moreover, % DLco and % VC were significantly decreased in SSc patients with anti- topo Ⅱ α Ab relative to those without the Ab (P<0.05 and P<0.01, respectively). The elevated levels of both erythrocyte sedimentation rate and C- reactive protein were also more frequently observed in SSc patients positive for IgG anti- topo Ⅱ α Ab (P<0.005). The results of the present study indicate that anti- topo Ⅱ α Ab represent one of the autoantibody specificities detected on SSc patients and may be regarded a serological marker of pulmonary fibrosis in Japanese patients with SSc.
文摘Natural killer (NK) cells are innate immune effectors that produce various immunoregulatory cytokines. Recent studies have shown that NK cells are involved in the initiation of autoimmunity. In this study, we determined abnormalities of NK cells in systemic sclerosis (SSc), an autoimmune connective tissue disease, by assessing the frequency and absolute number, activation marker expression, cytokine production, and killing activity. The frequency and absolute number of NK cells increased in diffuse cutaneous SSc (dcSSc), whereas they were normal in limited cutaneous SSc (IcSSc). NK cells from both dcSSc and IcSSc patients exhibited activated phenotypes characterized by up-regulated CD16 and CD69 expression and downregulated CD62L expression. Interferon (IFN)-γ production by non-stimulated NK cells from both dcSSc and IcSSc patientswas increased compared to the normal control, whereas on stimulation, a reduced amount of IFN-γ was produced. Interleukin (IL)- 5 and IL- 10 production by non- stimulated NK cells and IL- 6 production by stimulated NK cells were augmented in dcSSc patients, but not in IcSSc patients. Despite the augmented cytokine production by non-stimulated NK cells, natural cytotoxicity activity and granzyme B secretion was reduced in NK cells from dcSSc and IcSSc patients. These results suggested that altered NK cell function contributes to immunological abnormalities in SSc.
文摘Background: The transforming growth factor-β(TGF-β) system plays a critical role both in systemic sclerosis (SSc) and hereditary hemorrhagic telangiectasia (HHT). Endoglin, known as a gene responsible for HHT, is a TGF-βreceptor preferentially expressed on endothelial cells. The role of endoglin in SSc is potentially intriguing since limited cutaneous SSc (IcSSc)-and HHT share several symptoms, including telangiectasia. Objective: To determine serum levels of soluble endoglin (sEndoglin) and clinical associations in patients with SSc. Methods: Serums Endoglin levels were examined by ELISA in 70 patients with SSc, 20 patients with systemic lupus erythematosus and 20 healthy individuals. Results: Serum sEndoglin levels were significantly elevated in patients with IcSSc compared with diffuse cutaneous SSc and systemic lupus erythematosus patients as well as normal controls. Patients with elevated sEndoglin levels had telangiectasia more frequently than those with normal sEndoglin levels. Furthermore, pulmonary artery pressure was positively correlated with sEndoglin levels in patients with IcSSc. Conclusion: Abnormal expression/function of endoglin may be linked to IcSSc-specific manifestations.
