文摘
摘要目的:检查的角色B细胞免疫病理的公差功能障碍anti-neurofascin 155 (nf - 155) autoantibody-mediated慢性炎性脱髓鞘多神经病(CIDP)。
背景:paranodal蛋白质的自身抗体nf - 155中5%的病人履行CIDP诊断标准。这些患者通常具有不同的临床表型和应对治疗B细胞耗竭。然而,B细胞功能障碍导致的pathomechanism nf - 155介导CIDP仍然未知。在这项研究中,我们检查了宽容B细胞功能障碍在nf - 155介导CIDP患者,这可能导致异常的自身抗体生产,并已与重症肌无力,neuromyelitis视,和其他自身免疫性疾病。
设计/方法:使用的方法,我们从单一的B细胞重组单克隆抗体生成的新移民(NE)和成熟的幼稚(MN)隔间nf - 155介导CIDP患者。polyreactive NE B细胞克隆的频率是衡量对dsDNA ELISA,胰岛素,脂多糖,评估中心B细胞容忍缺陷检查站。同样,HEp-2细胞的频率lysate-specific autoreactive MN B细胞克隆测定确定一个外围B细胞容忍缺陷检查站。
结果:74和30个独特的单克隆抗体克隆生成NE和MN B细胞的3 nf - 155介导CIDP患者,分别和47%(±36.2%)从东北B细胞克隆,32.3% (±13.2%)MN B细胞的克隆polyreactive,预计5 - 11%相比polyreactivity健康对照组。评估周边宽容检查点的缺陷和表现型NE和MN B细胞在单细胞水平的同时分析基因表达和完整的B细胞受体配对正在进行。
结论:初步分析表明,CIDP与nf - 155可能早期检查点容忍缺陷。进一步的研究是必要的理解的含义B细胞功能障碍疾病的免疫病理反应。
披露:罗伊博士已经收到个人薪酬在500 - 4999美元的范围作为顾问Alexion药品。罗伊博士已经收到个人薪酬在500 - 4999美元的范围为武田制药担任顾问。罗伊博士已经收到个人薪酬在500 - 4999美元的范围为argenx担任顾问。罗伊博士在Cabaletta生物股票。。罗伊博士的机构已经收到了来自Martin shubik2009基金研究支持IBM在耶鲁大学。Obaid女士没有披露。大桥女士没有披露。科波拉太太没有披露。Das先生没有披露。阿曼达·埃尔南德斯没有透露。 Dr. Masi has nothing to disclose. Mrs. Martín-Aguilar has nothing to disclose. Dr. Lleixa has nothing to disclose. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for argenx. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Momenta . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cabaletta Bio . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bio. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cour Pharma. The institution of Dr. Nowak has received research support from Ra Pharma. The institution of Dr. Nowak has received research support from Alexion . The institution of Dr. Nowak has received research support from Momenta . The institution of Dr. Nowak has received research support from Immunovant . Dr. Nowak has received research support from argenx. Dr. Nowak has received research support from Viela Bio . Dr. Nowak has a non-compensated relationship as a Member of the Board of Directors with Myasthenia Gravis Foundation of America (MGFA) that is relevant to AAN interests or activities. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL Behring. The institution of Dr. Querol has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB. The institution of Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson & Johnson. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ArgenX. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Grifols. The institution of Dr. Querol has received research support from GBS-CIDP Foundation International. The institution of Dr. Querol has received research support from Grifols. The institution of Dr. Querol has received research support from ISCIII. The institution of Dr. Querol has received research support from CIBERER. The institution of Dr. Querol has received research support from UCB. Kevin O’Connor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Kevin O’Connor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Kevin O’Connor has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genentech. Kevin O’Connor has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Viela Bio. Kevin O’Connor has received stock or an ownership interest from Cabaletta.
