Autoimmune response to proteasome activator 28alpha in patients with connective tissue diseases.
Autoimmune response to proteasome activator 28alpha in patients with connective tissue diseases.
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发表时间：
2004-02
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通讯作者：
M. Matsushita;Y. Takasaki;K. Takeuchi;Hirofumi Yamada;R. Matsudaira;H. Hashimoto
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作者：
M. Matsushita;Y. Takasaki;K. Takeuchi;Hirofumi Yamada;R. Matsudaira;H. Hashimoto
目的 测定各种结缔组织疾病患者针对蛋白酶体激活剂28α（PA28α）的自身免疫反应，并比较抗PA28α和抗Ki抗体的免疫反应性。方法 从 219 名患有各种结缔组织疾病的患者中获取血清样本。通过聚合酶链式反应产生编码全长人PA28α和Ki的cDNA。抗原表达为谷胱甘肽 S-转移酶 (GST) 融合蛋白。通过蛋白质印迹法研究血清对 PA28α 和 Ki 的免疫反应性。使用纯化的 Ki 抗原通过 ELISA 进行抑制测试。结果 23% 的系统性红斑狼疮 (SLE) 患者和 24% 的干燥综合征 (SS) 患者的血清中检测到抗 PA28α 抗体。这些比率明显高于其他风湿病的比率。由于PA28α和Ki都是PA28复合物的元件，并且它们的氨基酸序列具有40.2%的同源性，因此对PA28α的免疫反应性进行了进一步研究。在27份抗Ki阳性血清样本中，13份样本（48%）也与PA28α发生反应，表明抗PA28α和抗Ki抗体之间存在相关性。为了研究这一发现是否是由于 PA28α 和 Ki 抗原的交叉反应表位的存在，通过 ELISA 进行了抑制测试。与重组 PA28α 预孵育不会抑制对纯化 Ki 抗原的反应性。结论 SLE 和 SS 患者血清中抗 PA28α 抗体的检测明显较高。抗 PA28α 和 Ki 抗体之间的关系表明抗原驱动系统在诱导针对 PA28 复合物的自身免疫反应中的重要性。
OBJECTIVE To determine the autoimmune response against proteasome activator 28alpha (PA28alpha) in patients with various connective tissue diseases, and to compare the immunoreactivity between anti-PA28alpha and anti-Ki antibodies. METHODS Serum samples were obtained from 219 patients with various connective tissue diseases. cDNA encoding full-length human PA28alpha and Ki were produced by polymerase chain reaction. Antigens were expressed as glutathione S-transferase (GST) fusion proteins. The immunoreactivity of serum for PA28alpha and Ki was studied by Western blotting. An inhibition test was performed by ELISA using purified Ki antigen. RESULTS Anti-PA28alpha> antibody was detected in serum from 23% of patients with systemic lupus erythematosus (SLE) and 24% with Sjögren's syndrome (SS). These rates were significantly higher than those for the other rheumatic diseases. Since both PA28alpha and Ki are elements of the PA28 complex and their amino acid sequences share 40.2% homology, immunoreactivity to PA28alpha was studied further. Among 27 anti-Ki positive serum samples, 13 samples (48%) also reacted with PA28alpha, suggesting a relationship between anti-PA28alpha and anti-Ki antibodies. To investigate whether this finding was due to the presence of cross-reacting epitopes for PA28alpha and Ki antigens, an inhibition test was performed by ELISA. The reactivity to purified Ki antigen was not inhibited by preincubation with recombinant PA28alpha. CONCLUSION Detection of anti-PA28alpha antibody was significantly higher in serum from patients with SLE and SS. The relationship between anti-PA28alpha and Ki antibodies suggests the importance of an antigen-driven system in the induction of an autoimmune response to PA28 complex.