IRCCS Istituto delle Scienze Neurologiche di Bologna, Via Altura, 3 - 40139, Bologna, Italy.
Department of Pharmacy and Biotechnology (FaBiT), Laboratory of Human and General Physiology, University of Bologna, Via San Donato, 19/2 - 40126, Bologna, Italy.
Rev Neurosci. 2024 Jun 13;35(8):877-893. doi: 10.1515/revneuro-2024-0027. Print 2024 Dec 17.
Small fiber neuropathy (SFN) is a peripheral nerve condition affecting thin myelinated Aδ and unmyelinated C-fibers, characterized by severe neuropathic pain and other sensory and autonomic symptoms. A variety of medical disorders can cause SFN; however, more than 50% of cases are idiopathic (iSFN). Some investigations suggest an autoimmune etiology, backed by evidence of the efficacy of IVIG and plasma exchange. Several studies suggest that autoantibodies directed against nervous system antigens may play a role in the development of neuropathic pain. For instance, patients with CASPR2 and LGI1 antibodies often complain of pain, and and studies support their pathogenicity. Other antibodies have been associated with SFN, including those against TS-HDS, FGFR3, and Plexin-D1, and new potential targets have been proposed. Finally, a few studies reported the onset of SFN after COVID-19 infection and vaccination, investigating the presence of potential antibody targets. Despite these overall findings, the pathogenic role has been demonstrated only for some autoantibodies, and the association with specific clinical phenotypes or response to immunotherapy remains to be clarified. The purpose of this review is to summarise known autoantibody targets involved in neuropathic pain, putative attractive autoantibody targets in iSFN patients, their potential as biomarkers of response to immunotherapy and their role in the development of iSFN.
小纤维神经病 (SFN) 是一种影响细有髓鞘 Aδ 和无髓鞘 C 纤维的周围神经疾病，其特征是严重的神经病理性疼痛和其他感觉及自主神经症状。多种医学疾病均可引起 SFN；然而，超过 50%的病例为特发性 (iSFN)。一些研究提示存在自身免疫病因，静脉注射免疫球蛋白和血浆置换的疗效为此提供了证据支持。几项研究表明，针对神经系统抗原的自身抗体可能在神经病理性疼痛的发展中起作用。例如，具有 CASPR2 和 LGI1 抗体的患者常诉疼痛，且 和 研究支持其致病性。其他抗体也与 SFN 相关，包括针对 TS-HDS、FGFR3 和 Plexin-D1 的抗体，并且已经提出了新的潜在靶点。最后，有一些研究报告了 COVID-19 感染和接种疫苗后 SFN 的发病，调查了潜在抗体靶标的存在。尽管有这些总体发现，但仅对一些自身抗体证实了其致病作用，并且与特定的临床表型或免疫治疗反应的关联仍有待阐明。本综述的目的是总结已知与神经病理性疼痛相关的自身抗体靶标、iSFN 患者中假定的有吸引力的自身抗体靶标、它们作为免疫治疗反应的生物标志物的潜力及其在 iSFN 发展中的作用。
