Amyes E, Curnow J, Stark Z, Corlett L, Sutton I, Vincent A
Neurosciences Group Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK.
J Neuroimmunol. 2001 Mar 1;114(1-2):259-64. doi: 10.1016/s0165-5728(00)00445-8.
Paraneoplastic cerebellar degeneration (PCD) occurs as a non-metastatic manifestation of cancer in a small proportion of patients with certain breast or gynaecological tumours, and is characterised by widespread Purkinje cell loss. Antibodies against a Purkinje cell cytoplasmic antigen, called Yo, that is expressed by the tumours, are present in the majority of these patients, but the pathogenic role of the antibodies is not clear. To characterise further the immune response in these cases, 13 anti-Yo positive sera were tested for IgG subclasses by immunohistochemistry and western blotting and, in four cases, PHA-stimulated cytokine secretion by peripheral blood lymphocytes was measured. Surprisingly, anti-Yo antibodies were entirely restricted to the IgG1 subclass, whereas antibodies against the small cell cancer-associated antigen, Hu, were found in all four IgG subclasses. There was a trend towards raised IgG1 levels in the total IgG of the anti-Yo positive patients and, in two, PHA-stimulated peripheral blood lymphocytes secreted raised levels of IFN-gamma. By contrast, in the other two cases tested, raised levels of IL-4 were secreted. Patients with PCD associated with anti-Yo antibodies appear to have strong immune responses that are polarised with respect to the IgG subclass and Th cytokine profiles.
副肿瘤性小脑变性（PCD）是某些乳腺癌或妇科肿瘤患者中一小部分人出现的癌症非转移性表现，其特征是广泛的浦肯野细胞丢失。这些患者中的大多数体内存在针对肿瘤表达的一种名为Yo的浦肯野细胞胞质抗原的抗体，但其致病作用尚不清楚。为了进一步明确这些病例中的免疫反应特征，通过免疫组织化学和蛋白质印迹法对13份抗Yo阳性血清进行了IgG亚类检测，并在4例病例中检测了外周血淋巴细胞经PHA刺激后的细胞因子分泌情况。令人惊讶的是，抗Yo抗体完全局限于IgG1亚类，而抗小细胞癌相关抗原Hu的抗体在所有4种IgG亚类中均有发现。抗Yo阳性患者的总IgG中IgG1水平有升高趋势，其中2例经PHA刺激的外周血淋巴细胞分泌的IFN-γ水平升高。相比之下，在另外2例检测病例中，分泌的IL-4水平升高。与抗Yo抗体相关的PCD患者似乎具有强烈的免疫反应，在IgG亚类和Th细胞因子谱方面呈极化状态。
