Sillevis Smitt P, Manley G, Dalmau J, Posner J
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
J Neuroimmunol. 1996 Dec;71(1-2):199-206. doi: 10.1016/s0165-5728(96)00153-1.
Patients with small-cell carcinoma of the lung and paraneoplastic encephalomyelitis develop antibodies (anti-Hu) against HuD, a member of a family of neuronal specific RNA-binding proteins, which are also expressed by the tumor. In order to determine if the human HuD paraneoplastic antigen shares immunogenic regions between patients and several strains and species of animals, we immunized animals with HuD and several deletion constructs of this protein. All immunized animals developed high titers of anti-HuD antibodies, comparable to the antibody titers found in paraneoplastic patients. Using immunohistochemistry and Western blot analysis of human and mouse cerebral cortex, the pattern of reactivity of these antibodies could not be differentiated from the human paraneoplastic anti-Hu antibodies. None of the immunized animals developed neurologic symptoms. Western blot analysis of HuD deletion constructs demonstrated that the first and second RNA binding domains were the main immunodominant regions, and that the animal immune response was both strain and species dependent.
患有小细胞肺癌和副肿瘤性脑脊髓炎的患者会产生针对HuD的抗体（抗Hu），HuD是神经元特异性RNA结合蛋白家族的一员，肿瘤细胞也会表达该蛋白。为了确定人类HuD副肿瘤抗原在患者与几种动物品系和物种之间是否具有共同的免疫原性区域，我们用HuD和该蛋白的几种缺失构建体免疫动物。所有免疫动物都产生了高滴度的抗HuD抗体，与副肿瘤患者体内发现的抗体滴度相当。通过对人和小鼠大脑皮层进行免疫组织化学和蛋白质印迹分析，这些抗体的反应模式与人类副肿瘤抗Hu抗体无法区分。没有一只免疫动物出现神经症状。对HuD缺失构建体的蛋白质印迹分析表明，第一个和第二个RNA结合结构域是主要的免疫显性区域，并且动物的免疫反应既依赖于品系也依赖于物种。
