Glyceraldehyde 3-phosphate dehydrogenase is a novel autoantigen leading autoimmune responses to proliferating cell nuclear antigen multiprotein complexes in lupus patients.
Glyceraldehyde 3-phosphate dehydrogenase is a novel autoantigen leading autoimmune responses to proliferating cell nuclear antigen multiprotein complexes in lupus patients.
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DOI：
10.1093/intimm/dxh131
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发表时间：
2004-09
影响因子：
4.4
通讯作者：
Y. Takasaki;K. Kaneda;M. Matsushita;Hirofumi Yamada;M. Nawata;R. Matsudaira;M. Asano;R. Mineki;N. Shindo;H. Hashimoto
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文献类型：
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作者：
Y. Takasaki;K. Kaneda;M. Matsushita;Hirofumi Yamada;M. Nawata;R. Matsudaira;M. Asano;R. Mineki;N. Shindo;H. Hashimoto
使用二维电泳和离子对色谱法，我们已经确定了增殖细胞核抗原（PCNA）多蛋白复合物的元素，从系统性红斑狼疮患者的血清中的抗体反应。在复合物的各种元素中，一种37 kDa的蛋白质（PI 8.5）与SLE血清特异性反应，但不与其他结缔组织疾病患者的血清反应，被鉴定为甘油醛3-磷酸脱氢酶（GAPDH）。免疫印迹分析表明，与37 kDa蛋白反应的SLE血清特异性地与GAPDH反应，抗GAPDH单克隆抗体也是如此。从狼疮血清中纯化的抗GAPDH自身抗体在Hep-2细胞上的免疫荧光显示核斑点和胞浆染色模式。此外，酶联免疫吸附试验（ELISA）显示，在47%的狼疮患者存在抗GAPDH自身抗体。狼疮血清PCNA复合物的反应性的纵向分析表明，自身免疫反应从GAPDH扩散到PCNA复合物的其他元素，抗GAPDH抗体的存在与血清PCNA水平的增加显着相关。两者合计，这些研究结果表明，GAPDH与PCNA的细胞功能相关的相互作用是一种新的自身抗原识别的狼疮血清，GAPDH因此在诱导自身免疫反应对PCNA复合物中起着重要的作用。
Using 2-dimensional electrophoresis and ion-pair chromatography, we have identified elements of proliferating cell nuclear antigen (PCNA) multiprotein complexes that are reactive to antibodies in sera from patients with systemic lupus erythematosus. Among the various elements of the complexes, a 37 kDa protein (PI 8.5) that specifically reacted with SLE sera, but not with sera from patients with other connective tissue diseases, was identified as glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Immunoblot analysis showed that SLE sera reactive with the 37 kDa protein specifically reacted with GAPDH, as did anti-GAPDH mAbs. The purified autoantibodies to GAPDH from lupus serum showed both nuclear speckled and cytoplasmic staining patterns in immunofluorescence on Hep-2 cells. In addition, enzyme-linked immunosorbent assay (ELISA) revealed the presence of anti-GAPDH autoantibodies in 47% of lupus patients. Longitudinal analysis of the reactivity of lupus sera to PCNA complexes showed the autoimmune response to spread from GAPDH to other elements of PCNA complexes, and the presence of anti-GAPDH antibodies was significantly correlated with increased levels of serum PCNA. Taken together, these findings suggest that GAPDH interacting with PCNA in association with its cellular function is a novel autoantigen recognized by lupus sera, and that GAPDH thus plays an important role in the induction of autoimmune responses against the PCNA complex.