Autoantibody against peroxiredoxin I, an antioxidant enzyme, in patients with systemic sclerosis: possible association with oxidative stress
Autoantibody against peroxiredoxin I, an antioxidant enzyme, in patients with systemic sclerosis: possible association with oxidative stress
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DOI：
10.1093/rheumatology/kem010
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发表时间：
2007-05-01
期刊：
影响因子：
5.5
通讯作者：
Sato, S.
中科院分区：
文献类型：
--
作者：
Iwata, Y.;Ogawa, F.;Sato, S.
目标。目的：探讨系统性硬化症（SSc）患者抗氧化酶过氧化物还蛋白（Prx） I自身抗体的流行及临床相关性。采用ELISA法检测SSc患者（70例）和健康对照（23例）血清中Prx I抗体的表达，免疫印迹法检测抗Prx I抗体的存在。为了确定抗Prx I抗体在体内的功能相关性，我们利用酵母硫氧还蛋白还原酶系统评估了抗Prx I抗体是否能够抑制Prx I酶的活性。SSc患者IgG抗prx I抗体水平明显高于健康对照组，33%的SSc患者检测到这种自身抗体。IgG抗prx I抗体的存在与疾病持续时间更长、肺纤维化、心脏受累更频繁、抗拓扑异构酶I抗体的存在以及血清免疫球蛋白和红细胞沉降率升高有关。IgG抗prx I抗体水平与肾血管损伤呈正相关，与肺功能测试呈负相关。此外，抗prx I抗体水平与血清8-异前列腺素水平呈正相关，8-异前列腺素是氧化应激的标志物。免疫印迹分析证实存在抗prx I抗体。从含有抗Prx - 1抗体的SSc血清中分离的IgG明显抑制Prx - 1酶活性。上述结果提示，抗prxi自身抗体IgG升高与SSc疾病严重程度相关，抗prxi抗体可能通过抑制PrxI酶活性增强氧化应激。
Objectives. To determine the prevalence and clinical correlation of autoantibody to peroxiredoxin (Prx) I, an antioxidant enzyme, in patients with systemic sclerosis (SSc).Methods. Serum samples from SSc patients (n = 70) and healthy controls (n = 23) were examined by ELISA using human recombinant Prx I. The presence of anti-Prx I antibody was further evaluated by immunoblotting analysis. To determine the functional relevance of anti-Prx I antibody in vivo, we assessed whether anti-Prx I antibody was able to inhibit Prx I enzymatic activity using yeast thioredoxin reductase system.Results. IgG anti-Prx I antibody levels in SSc patients were significantly higher than healthy controls and this autoantibody was detected in 33% of SSc patients. The presence of IgG anti-Prx I antibody was associated with longer disease duration, more frequent presence of pulmonary fibrosis, heart involvement, and anti-topoisomerase I antibody and increased levels of serum immunoglobulin and erythrocyte sedimentation rates. IgG anti-Prx I antibody levels also correlated positively with renal vascular damage and negatively with pulmonary function tests. Furthermore, anti-Prx I antibody levels correlated positively with serum levels of 8-isoprostane, a marker of oxidative stress. Immunoblotting analysis confirmed the presence of anti-Prx I antibody. Remarkably, Prx I enzymatic activity was inhibited by IgG isolated from SSc sera containing IgG anti-Prx I antibody.Conclusions. These results suggest that elevated IgG anti-Prx I autoantibody is associated with the disease severity of SSc and that anti-PrxI antibody may enhance the oxidative stress by inhibiting Prx I enzymatic activity.