کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
7279455 1473897 2018 8 صفحه PDF سفارش دهید دانلود رایگان
عنوان انگلیسی مقاله ISI
Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum
ترجمه فارسی عنوان
اتصال دیفرانسیل آنتی بادی ها در بیماران پانداس به اینترنورون های کولینرژیک در استریاتوم
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موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
چکیده انگلیسی
Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus, or PANDAS, is a syndrome of acute childhood onset of obsessive-compulsive disorder and other neuropsychiatric symptoms in the aftermath of an infection with Group A beta-hemolytic Streptococcus (GABHS). Its pathophysiology remains unclear. PANDAS has been proposed to result from cross-reactivity of antibodies raised against GABHS with brain antigens, but the targets of these antibodies are unclear and may be heterogeneous. We developed an in vivo assay in mice to characterize the cellular targets of antibodies in serum from individuals with PANDAS. We focus on striatal interneurons, which have been implicated in the pathogenesis of tic disorders. Sera from children with well-characterized PANDAS (n = 5) from a previously described clinical trial (NCT01281969), and matched controls, were infused into the striatum of mice; antibody binding to interneurons was characterized using immunofluorescence and confocal microscopy. Antibodies from children with PANDAS bound to ∼80% of cholinergic interneurons, significantly higher than the <50% binding seen with matched healthy controls. There was no elevated binding to two different populations of GABAergic interneurons (PV and nNOS-positive), confirming the specificity of this phenomenon. Elevated binding to cholinergic interneurons resolved in parallel with symptom improvement after treatment with intravenous immunoglobulin. Antibody-mediated dysregulation of striatal cholinergic interneurons may be a locus of pathology in PANDAS. Future clarification of the functional consequences of this specific binding may identify new opportunities for intervention in children with this condition.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain, Behavior, and Immunity - Volume 69, March 2018, Pages 304-311
نویسندگان
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