Husby G, Li L, Davis L E, Wedege E, Kokmen E, Williams R C
J Clin Invest. 1977 May;59(5):922-32. doi: 10.1172/JCI108714.
Antibodies reacting with neuronal cytoplasmic antigens present in normal human caudate and subthalamic nuclei were detected in 37 of 80 probands afflicted with Huntington's disease (HD). IgG antibodies were detected by immunofluorescence using frozen sections of unfixed normal human and rat brain. Specificity of IgG binding was confirmed using pepsin F(ab')2 fragments of IgG isolated from positive sera. In vitro complement fixation of IgG antibody was detected in 22 of 31 sera tested. Neuronal cytoplasmic antigens reacting with positive HD sera were diminished after trypsin or RNAase treatment of tissue sections but were not removed by DNAase, neuraminidase, EDTA, or dithiothreitol treatment. Antibody staining of neurons could be removed after absorption with isolated caudate nucleus neurons or by using perchloroacetic acid extracts of caudate nucleus. Prevalence of antibody reacting with neuronal cytoplasm was 3% in 60 normal controls and 6% among a wide variety of patients with diverse neurological disorders. However, one-third of 33 patients with Parkinson's disease showed presence of antineuronal antibody. Among patients with HD, a significant association was noted between duration of clinical disease greater than 7 yr and titers of antibody of 1:2 or greater (P less than 0.001). When 115 family members of HD probands were tested, 30% of unaffected spouses showed presence of antineuronal antibody. 23.2% of first-degree relatives at risk for developing HD was also positive (P less than 0.001). 10.5% of second-degree relatives showed presence of antineuronal antibody. These data may support an environmental or infectious factor somehow involved in the ultimate expression of HD.
在80例亨廷顿舞蹈症（HD）患者中，有37例检测出与正常人尾状核和丘脑底核中存在的神经元胞浆抗原发生反应的抗体。通过对未固定的正常人和大鼠脑冰冻切片进行免疫荧光检测IgG抗体。使用从阳性血清中分离出的IgG的胃蛋白酶F(ab')2片段证实了IgG结合的特异性。在31份检测血清中，有22份检测到IgG抗体的体外补体结合。经胰蛋白酶或RNA酶处理组织切片后，与HD阳性血清发生反应的神经元胞浆抗原减少，但经DNA酶、神经氨酸酶、EDTA或二硫苏糖醇处理后未被去除。用分离的尾状核神经元吸收或使用尾状核的过氯酸提取物后，可去除神经元的抗体染色。在60名正常对照者中，与神经元胞浆发生反应的抗体患病率为3%，在各种神经系统疾病患者中为6%。然而，33例帕金森病患者中有三分之一显示存在抗神经元抗体。在HD患者中，临床疾病持续时间大于7年与抗体滴度为1:2或更高之间存在显著关联（P<0.001）。对115名HD患者的家庭成员进行检测时，30%未受影响的配偶显示存在抗神经元抗体。有患HD风险的一级亲属中23.2%也呈阳性（P<0.001）。二级亲属中有10.5%显示存在抗神经元抗体。这些数据可能支持某种环境或感染因素以某种方式参与了HD的最终表现。
