PT -期刊文章盟克里斯蒂娜帕特森AU -伊丽莎白Burnor盟Amit酒吧或非盟-埃里克·兰开斯特TI -机制的贡献IgG4自身抗体在自身免疫性neurofascins脱髓鞘疾病(S21.004) DP - 2019年4月09年TA -神经病学PG - S21.004 VI - 92 IP - 15补充4099 - //www.ez-admanager.com/content/92/15_Supplement/S21.004.short 4100 - //www.ez-admanager.com/cont首页ent/92/15_Supplement/S21.004.full所以Neurology2019 4月09年;92 AB -目的:确定neurofascins自身抗体的致病机制。背景:机制自身抗体对细胞粘附分子表达有髓鞘的轴突可能导致受伤和神经疾病知之甚少。自身抗体Neurofascin 155 (NF155)定义了一个子集的患者严重的获得性脱髓鞘神经病变和通常的IgG4子类。IgG4,与其他免疫球蛋白亚型,经历hemi-antibody交换使每个抗体bi-specific(功能单价),这种交联,内化目标抗原的可能性不大。在paranode NF155与contactin / Caspr复杂,一个协会所必需的锚定轴突髓鞘。NF155也是二聚体外,尽管这种交互的功能的影响是不清楚。我们假设IgG4自身抗体破坏重要异染的和NF155的亲同种抗原的交互作用,反过来,可能会破坏蛋白质的功能。设计/方法:使用细胞试验筛选,我们证实了存在NF155自身抗体在脱髓鞘神经病变患者的一个子集。固相结合分析法是用于测试的影响NF155自身抗体的绑定NF155 contactin, Caspr, neurofascin体外。结果:我们发现4例获得脱髓鞘病变窝藏NF155血清自身抗体。NF155 IgG4自身抗体被发现在所有情况下,通常由主要的亚型。 In binding assays, NF155 bound contactin and neurofascin with nanomolar affinity, while NF155 and Caspr did not appear to directly interact. Antibodies to neurofascin had a very modest effect on the interaction of NF155 with contactin; however, these neurofascin antibodies modulated homophilic neurofascin interactions.Conclusions: Our results suggest that inhibition of important protein-protein interactions is a possible mechanism of NF155 IgG4 autoantibodies and that homophilic NF155 interactions may play an as yet undefined role in myelination. Future work will focus on further characterizing homophilic NF155 interactions.Disclosure: Dr. Patterson has nothing to disclose. Dr. Burnor has nothing to disclose. Dr. Bar-Or has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Atara Biotherapeutics, Biogen, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, Medimmune, Merck/EMD Serono, Novartis, Sanofi-Genzyme. Dr. Bar-Or has received research support from Atara Biotherapeutics, Biogen, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, Medimmune, Merck/EMD Serono, Novartis, Sanofi-Genzyme. Dr. Lancaster has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Grifols Inc., Novartis, Merck. Dr. Lancaster has received royalty, license fees, or contractual rights payments from Novartis. Dr. Lancaster has received research support from Grifols Inc..