McCormick T S, Rowland E C
Ohio University, Department of Biological Sciences, Athens 45701.
Exp Parasitol. 1993 Nov;77(3):273-81. doi: 10.1006/expr.1993.1085.
The production of autoimmune antibodies during infection with the hemoflagellate parasite Trypanosoma cruzi has been previously reported by this and other laboratories. The present investigation indicates a potential target in normal heart tissue that may be the binding site for the autoimmune antibodies. Using Western blot analysis, sera obtained from chronically infected C57 B1/6 mice was examined for its ability to recognize normal tissue antigens from uninfected syngeneic animals. Antibodies from chronic sera recognized an antigen in normal mouse heart and skeletal muscle tissue at a molecular weight between 43 and 45 kilodaltons (kDa). This proposed target antigen was found in cytoplasmic extracts from normal heart antigen preparations. The autoantibody recognition of the normal tissue in Western blots was inhibited by periodate oxidation of the antigen sample. This suggests that the binding of the autoantibodies may be dependent upon a glycosylation present on the antigen targets. Isotype analysis indicated that the autoreactive antibodies are of the IgM and IgG2b isotypes. These results suggest that a target for autoantibodies in Chagas' disease may be a 43- to 45-kDa glycoprotein found in normal heart and skeletal muscle tissue. Exposure of the immune system to this antigen may follow the damaging effects of the parasite itself, or of the immune response toward the parasite. In either scenario the identification of a target in the ongoing autoimmunity may help to define the autoimmune process in American Trypanosomiasis.
本实验室及其他实验室之前曾报道过,在感染血液鞭毛虫寄生虫克氏锥虫期间会产生自身免疫抗体。目前的研究表明,正常心脏组织中可能存在一个潜在靶点,它可能是自身免疫抗体的结合位点。通过蛋白质免疫印迹分析,检测了从慢性感染的C57 B1/6小鼠获得的血清识别未感染同基因动物正常组织抗原的能力。慢性血清中的抗体识别正常小鼠心脏和骨骼肌组织中一种分子量在43至45千道尔顿(kDa)之间的抗原。在正常心脏抗原制剂的细胞质提取物中发现了这种推测的靶抗原。在蛋白质免疫印迹中,抗原样品经高碘酸盐氧化后,对正常组织的自身抗体识别受到抑制。这表明自身抗体的结合可能依赖于抗原靶点上存在的糖基化。同种型分析表明,自身反应性抗体为IgM和IgG2b同种型。这些结果表明,恰加斯病中自身抗体的一个靶点可能是在正常心脏和骨骼肌组织中发现的一种43至45 kDa的糖蛋白。免疫系统接触这种抗原可能是在寄生虫本身或针对寄生虫的免疫反应产生破坏作用之后。在这两种情况下,确定正在进行的自身免疫中的一个靶点可能有助于明确美洲锥虫病中的自身免疫过程。