Greenlee J E, Burns J B, Rose J W, Jaeckle K A, Clawson S
Neurology Service, Veterans Affairs Medical Center, Salt Lake City, UT 84148, USA.
Acta Neuropathol. 1995;89(4):341-5. doi: 10.1007/BF00309627.
Paraneoplastic cerebellar degeneration accompanying gynecological or breast malignancies is frequently associated with an autoantibody response, termed "type I" or "anti-Yo" directed against cytoplasmic antigens of cerebellar Purkinje cells. The role of this antibody response in the pathogenesis of paraneoplastic cerebellar degeneration is unknown; however, it is also not known whether anti-Purkinje cell antibodies from the systemic circulation bind to target Purkinje cell antigens under the conditions of brain inflammation and blood-brain barrier disruption, which are frequently present at the onset of cerebellar symptoms. Inbred Lewis rats received intraperitoneal injections of type I or normal IgG in the setting of blood-brain barrier disruption induced by adoptive transfer of experimental allergic encephalomyelitis (EAE) and were killed after 24, 48, and 96 h. Brains of these animals were studied histologically for evidence of EAE and immunohistochemically for binding of human or endogenous rat IgG to target neurons. Rat IgG was detected around vessels and in Purkinje cells of all animals studied. Human IgG was detected around vessels of all animals. In animals examined 96h after receiving type I human IgG, human IgG was identified within processes of Purkinje cells and within occasional Purkinje cell bodies. Uptake of type I IgG by other cell types was not observed, and neuronal uptake of IgG was not seen in brains of animals receiving normal human IgG. Our data demonstrate that circulating type I IgG is internalized by cerebellar Purkinje cells in the setting of blood-brain barrier disruption and suggest a mechanism by which an antibody response directed against cytoplasmic antigens of Purkinje cells may reach target antigens at the onset of paraneoplastic cerebellar degeneration.
妇科或乳腺恶性肿瘤伴发的副肿瘤性小脑变性常与一种自身抗体反应相关，这种反应被称为“Ⅰ型”或“抗Yo”，针对小脑浦肯野细胞的胞质抗原。这种抗体反应在副肿瘤性小脑变性发病机制中的作用尚不清楚；然而，在脑炎症和血脑屏障破坏（这在小脑症状发作时经常出现）的情况下，来自体循环的抗浦肯野细胞抗体是否会与靶浦肯野细胞抗原结合也不清楚。近交系Lewis大鼠在通过实验性自身免疫性脑脊髓炎（EAE）的过继转移诱导血脑屏障破坏的情况下，腹腔注射Ⅰ型或正常IgG，并在24、48和96小时后处死。对这些动物的大脑进行组织学研究以寻找EAE的证据，并进行免疫组织化学研究以检测人或内源性大鼠IgG与靶神经元的结合情况。在所研究的所有动物的血管周围和浦肯野细胞中均检测到大鼠IgG。在所有动物的血管周围均检测到人类IgG。在接受Ⅰ型人IgG 96小时后检查的动物中，在浦肯野细胞的突起内和偶尔的浦肯野细胞体内发现了人类IgG。未观察到其他细胞类型摄取Ⅰ型IgG，在接受正常人IgG的动物大脑中也未见到神经元摄取IgG。我们的数据表明，在血脑屏障破坏的情况下，循环的Ⅰ型IgG被小脑浦肯野细胞内化，并提示了一种机制，通过该机制，针对浦肯野细胞胞质抗原的抗体反应可能在副肿瘤性小脑变性发作时到达靶抗原。
