Morris Christina M, Pardo-Villamizar Carlos, Gause Colin D, Singer Harvey S
Department of Neurology, Pathology 235, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
J Neurol Sci. 2009 Jan 15;276(1-2):45-8. doi: 10.1016/j.jns.2008.08.032. Epub 2008 Sep 27.
PANDAS and some cases of Tourette syndrome (TS) have been proposed to be post-streptococcal movement disorders in which antibodies produced against group A beta-hemolytic streptococcus cross react against brain epitopes. Attempts to identify disease specific anti-striatal antibodies in the serum of affected patients have focused on the use of Western immunoblotting and ELISA methodologies. In this study, immunohistochemical techniques were used to identify serum anti-striatal antibody reactivity. In positive samples, double staining with anti-GFAP (glial) and anti-MAP2 (neuronal) was used to establish localization of the immunofluorescence. No significant differences in immunofluorescence or localization were identified in patients with PANDAS (n=30) and TS (n=30) as compared to controls (n=30). IF reactivity did not correlate with tic severity or elevated titers of antistreptococcal antibodies. Further comparisons showed no correlation between autoreactivity determined by immunofluorescence and the presence of previously measured immunoblot reactivity against human caudate or putative antigens (pyruvate kinase M1 and aldolase C). These results confirm an inability to distinguish patient populations by antibody measurements and raise further concerns about the presence of an autoimmune mechanism in PANDAS and TS.
PANDAS和一些抽动秽语综合征(TS)病例被认为是链球菌感染后运动障碍,其中针对A组β溶血性链球菌产生的抗体与脑表位发生交叉反应。在受影响患者的血清中鉴定疾病特异性抗纹状体抗体的尝试主要集中在使用蛋白质免疫印迹法和酶联免疫吸附测定法。在本研究中,采用免疫组织化学技术鉴定血清抗纹状体抗体反应性。在阳性样本中,使用抗GFAP(神经胶质)和抗MAP2(神经元)双重染色来确定免疫荧光的定位。与对照组(n = 30)相比,PANDAS患者(n = 30)和TS患者(n = 30)在免疫荧光或定位方面未发现显著差异。免疫荧光反应性与抽动严重程度或抗链球菌抗体滴度升高无关。进一步比较显示,通过免疫荧光测定的自身反应性与先前测定的针对人尾状核或推定抗原(丙酮酸激酶M1和醛缩酶C)的蛋白质免疫印迹反应性之间没有相关性。这些结果证实无法通过抗体测量来区分患者群体,并进一步引发了对PANDAS和TS中自身免疫机制存在的担忧。