软骨结合抗体通过免疫复合物介导的神经元激活诱发疼痛
神经元与认知
2019-08-16 v1 组织与器官
摘要
类风湿关节炎相关的关节疼痛常独立于疾病活动度而被观察到，提示存在未知的疼痛机制。我们证明，结合软骨、特异性针对 II 型胶原（CII）或软骨寡聚基质蛋白（COMP）的抗体在小鼠中引发机械性 hypersensitivity，且与炎症的肉眼、组织学和分子指征脱钩。软骨抗体诱发的疼痛样行为不依赖于补体激活或关节炎症，而是依赖于组织抗原识别与局部免疫复合物（IC）形成。smFISH 和 IHC 提示神经元 Fcgr1 和 Fcgr2b mRNA 被运输至初级传入神经的外周末端。CII-IC 直接激活培养的 WT 而非 FcR{\gamma} 链缺陷的 DRG 神经元。与之一致，CII-IC 不在 FcR{\gamma} 链缺陷小鼠中诱发机械性 hypersensitivity。此外，CII 抗体注射不在 FcR{\gamma} 链缺陷小鼠或神经元中缺失激活型 Fc{\gamma}R 的小鼠中产生疼痛样行为。总之，本研究定义了自身抗体与疼痛传导之间的功能性耦合，可能促进新的疾病相关疼痛疗法的发展。
引用
@article{arxiv.1908.05298,
title = {Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons},
author = {Alex Bersellini Farinotti and Gustaf Wigerblad and Diana Nascimento and Duygu B Bas and Carlos Morado Urbina and Kutty Selva Nandakumar and Katalin Sandor and Bingze Xu and Sally Abdelmoaty and Matthew A Hunt and Kristina Ängeby Möller and Azar Baharpoor and Jon Sinclair and Kent Jardemark and Johanna T Lanner and Ia Khmaladze and Lars E. Borm and Lu Zhang and Fredrik Wermeling and Mark S Cragg and Johan Lengqvist and Anne-Julie Chabot-Doré and Luda Diatchenko and Inna Belfer and Mattias Collin and Kim Kultima and Birgitta Heyman and Juan M. Jimenez-Andrade and Simone Codeluppi and Rikard Holmdahl and Camilla I Svensson},
journal= {arXiv preprint arXiv:1908.05298},
year = {2019}
}