文摘
客观的研究神经元的机制多种和其他抗体。
背景我们实验室曾表明,神经元可以占用正常和多种免疫球蛋白,多种自身抗体,如anti-Yo和anti-Hu可以绑定他们的细胞内靶抗原产生神经元死亡。在这项研究中我们调查如何神经元抗体吸收发生。
设计/方法我们首先比较神经的正常和多种Fab片段与正常免疫球蛋白Fc碎片或整个多种免疫球蛋白。确定神经元表达受体能够绑定的Fc部分免疫球蛋白分子,paraformaldehyde-fixed老鼠和老鼠的大脑部分探索了Fc受体抗体的三种主要类型:FcγRI (CD64) FcγRII, (CD32)和FcγRIII (CD16)。神经元吸收antineuronal免疫球蛋白g之间比较野生型小鼠和基因敲除小鼠缺乏FcγRI受体。我们也调查了神经免疫球蛋白吸收是否可以被正常的免疫球蛋白。
结果神经元包含正常免疫球蛋白的Fc片段而不是Fab片段。完整的多种免疫球蛋白是由神经元,但immunospecific Fab片段被排除在外。神经元在大脑、小脑和脑干显示immunolabeling FcγRI,但只有罕见的神经元FcγRII或者FcγRIII表示。吸收多种免疫球蛋白和神经元死亡的文化中,并未观察到FcγRI基因敲除小鼠,但广泛的文化从野生型控制。多种的正常免疫球蛋白抗体可以抑制吸收。
结论神经元的正常和多种免疫球蛋白g需要交互的Fc部分免疫球蛋白分子与之前无特征神经FcγRI受体。我们的研究提供了一种机制,通过抗体与细胞内的神经元活性蛋白质可以获得他们的目标抗原引起神经损伤和神经系统疾病。观察神经元抗体吸收能被正常免疫球蛋白对病人有可能影响治疗。
脚注
披露:史密斯博士没有披露。刘博士的直系亲属成员的机构已收到NIH的研究支持。Carlson先生的机构收到生原体的研究支持。Carlson先生已经收到个人薪酬在100000 - 499999美元的范围作为员工与退伍军人事务研究员。Clardy博士获得了个人作为一个雇员补偿退伍军人健康管理局(VHA)。Clardy博士已经收到个人赔偿作为犹他大学的员工的健康。Clardy博士已经收到个人补偿的范围0 - 499美元为号角担任顾问。Clardy博士已经收到个人薪酬在500 - 4999美元的范围为ExpertConnect担任顾问。Clardy博士的机构已收到个人补偿的范围0 - 499美元为VielaBio担任顾问。Clardy博士的机构已收到个人补偿的范围0 - 499美元为基因泰克公司担任顾问。 The institution of Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Clardy has received personal compensation in the range of $0-$499 for serving as a Consultant for GuidePoint. Dr. Clardy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology/AAN Publications. The institution of Dr. Clardy has received research support from Alexion Pharma. The institution of Dr. Clardy has received research support from Sumaira Foundation for NMO. The institution of Dr. Clardy has received research support from Immune Deficiency Foundation. The institution of Dr. Clardy has received research support from Western Institute for Veteran Research. The institution of Dr. Clardy has received research support from NIH/NINDS. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a AAN Summer Meeting CoDirector Travel and Lodging with AAN. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel and Lodging with U of Iowa. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Barrow Neurological Institute. Dr. Greenlee has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medlink. Dr. Greenlee has received publishing royalties from a publication relating to health care. Dr. Greenlee has received publishing royalties from a publication relating to health care.
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