Anti-streptococcus IgM antibodies induce repetitive stereotyped movements: Cell activation and co-localization with Fc¦Á/¦Ì receptors in the striatum and motor cortex

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• 作者：Danhui Zhang^a ; Ankur Patel^a ; ^b ; ^{dr.ankur@yahoo.com} ; Youhua Zhu^a ; Allan Siegel^a ; ^b ; Steven S. Zalcman^a
• 关键词：Group A beta-hemolytic streptococcus ; Stereotypy ; Obsessive&ndash ; compulsive disorder ; Tics ; Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection
• 刊名：Brain, Behavior, and Immunity
• 出版年：2012
• 出版时间：May, 2012
• 年：2012
• 卷：26
• 期：4
• 页码：521-533
• 全文大小：1906 K

文摘

Group A beta-hemolytic streptococcus (GABHS) infections are implicated in neuropsychiatric disorders associated with an increased expression of repetitive stereotyped movements. Anti-streptococcus IgG presumably cross-reacts with elements on basal ganglia cells, modifies their function, and triggers symptoms. IgM may play a unique role in precipitating behavioral disturbances since variations in cortico-striatal activity occur in temporal congruity with peak IgM titers during an orchestrated immune response. We discovered in Balb/c mice that single subcutaneous injections of mouse monoclonal IgM antibodies to streptococcus group A bacteria induce marked dose-dependent increases in repetitive stereotyped movements, including head bobbing, sniffing, and intense grooming. Effects were antibody- and antigen-specific: anti-streptococcus IgG stimulated ambulatory activity and vertical activity but not these stereotypies, while anti-KLH IgM reduced activity. We suggest that anti-streptococcus IgM and IgG play unique roles in provoking GABHS-related behavioral disturbances. Paralleling its stereotypy-inducing effects, anti-streptococcus IgM stimulated Fos-like immunoreactivity in regions linked to cortico-striatal projections involved in motor control, including subregions of the caudate, nucleus accumbens, and motor cortex. This is the first evidence that anti-streptococcus IgM antibodies induce in vivo functional changes in these structures. Moreover, there was a striking similarity in the distributions of anti-streptococcus IgM deposits and Fos-like immunoreactivity in these regions. Of further importance, Fc¦Á/¦Ì receptors, which bind IgM, were present- and co-localized with anti-streptococcus IgM in these structures. We suggest that anti-streptococcus IgM-induced alterations of cell activity reflect local actions of IgM that involve Fc¦Á/¦Ì receptors. These findings support the use of anti-streptococcus monoclonal antibody administration in Balb/c mice to model GABHS-related behavioral disturbances and identify underlying mechanisms.