Hoffman Kurt L, Hornig Mady, Yaddanapudi Kavitha, Jabado Omar, Lipkin W Ian
Greene Infectious Disease Laboratory, Mailman School of Public Health, Columbia University, New York, New York 10032, USA.
J Neurosci. 2004 Feb 18;24(7):1780-91. doi: 10.1523/JNEUROSCI.0887-03.2004.
A syndrome of motoric and neuropsychiatric symptoms comprising various elements, including chorea, hyperactivity, tics, emotional lability, and obsessive-compulsive symptoms, can occur in association with group A beta-hemolytic streptococcal (GABHS) infection. We tested the hypothesis that an immune response to GABHS can result in behavioral abnormalities. Female SJL/J mice were immunized and boosted with a GABHS homogenate in Freund's adjuvant, whereas controls received Freund's adjuvant alone. When sera from GABHS-immunized mice were tested for immunoreactivity to mouse brain, a subset was found to be immunoreactive to several brain regions, including deep cerebellar nuclei (DCN), globus pallidus, and thalamus. GABHS-immunized mice having serum immunoreactivity to DCN also had increased IgG deposits in DCN and exhibited increased rearing behavior in open-field and hole-board tests compared with controls and with GABHS-immunized mice lacking serum anti-DCN antibodies. Rearing and ambulatory behavior were correlated with IgG deposits in the DCN and with serum immunoreactivity to GABHS proteins in Western blot. In addition, serum from a GABHS mouse reacted with normal mouse cerebellum in nondenaturing Western blots and immunoprecipitated C4 complement protein and alpha-2-macroglobulin. These results are consistent with the hypothesis that immune response to GABHS can result in motoric and behavioral disturbances and suggest that anti-GABHS antibodies cross-reactive with brain components may play a role in their pathophysiology.
一种包含多种元素的运动和神经精神症状综合征，包括舞蹈症、多动、抽搐、情绪不稳定和强迫症状，可与A组β溶血性链球菌（GABHS）感染相关联出现。我们检验了这样一种假设，即对GABHS的免疫反应可导致行为异常。雌性SJL/J小鼠用GABHS匀浆在弗氏佐剂中进行免疫和加强免疫，而对照组仅接受弗氏佐剂。当检测来自GABHS免疫小鼠的血清对小鼠脑的免疫反应性时，发现其中一部分血清对包括小脑深部核团（DCN）、苍白球和丘脑在内的几个脑区具有免疫反应性。对DCN具有血清免疫反应性的GABHS免疫小鼠，其DCN中的IgG沉积物也增加，并且与对照组以及缺乏血清抗DCN抗体的GABHS免疫小鼠相比，在旷场试验和洞板试验中表现出增加的竖毛行为。竖毛和走动行为与DCN中的IgG沉积物以及蛋白质印迹中血清对GABHS蛋白的免疫反应性相关。此外，来自一只GABHS小鼠的血清在非变性蛋白质印迹中与正常小鼠小脑发生反应，并免疫沉淀了C4补体蛋白和α-2-巨球蛋白。这些结果与以下假设一致，即对GABHS的免疫反应可导致运动和行为障碍，并表明与脑成分发生交叉反应的抗GABHS抗体可能在其病理生理学中起作用。
