Complement profiling of sural nerves in chronic-inflammatory demyelinating polyneuropathy

IF 9.3 1区 医学 Q1 CLINICAL NEUROLOGY
Frauke Stascheit, Andreas Roos, Christina B. Schroeter, Johanna Katrin Thomas, Katrin Hahn, Hannah Preßler, Andreas Hentschel, Beate Schlotter-Weigel, Benedikt Schoser, Tobias Ruck, Andreas Meisel, Werner Stenzel, Corinna Preusse
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引用次数: 0

Abstract

Chronic-inflammatory demyelinating polyneuropathy (CIDP) is a rare immune-mediated polyneuropathy causing substantial disability. While both cell-mediated and humoral mechanisms contribute to CIDP, the role of complement remains poorly understood. Considering the rise of complement-targeted treatment, it is crucial to examine the role of complement in CIDP. In this cross-sectional, study, sural nerve biopsies from 55 CIDP patients were analyzed using histopathology, gene- and protein-based techniques, comparing them to two non-diseased controls (NDCs), as well as 8 patients with hereditary neuropathy (HN) and idiopathic axonal neuropathy (IPN). Overall, 94% (n = 52) revealed abnormal and prominent deposition of terminal complement complex C5b-9 on endoneurial capillaries. Patients with significant complement deposition presented with a progressive disease course (n = 52) and the number and distribution of infiltrating CD8 + T cells and CD68 + macrophages, since a basic immunological paradigm holds that those two may form an immunological synapse, correlated with clinical disease severity as measured by inflammatory neuropathy cause and treatment sensory sum (INCAT) score (p < 0.001). Furthermore, changes in abundances of complement proteins as unveiled by untargeted proteomics accord with changes on transcript level as identified by targeted gene expression studies. In contrast, there was no complement deposition in NDC nor DC. This study provides an extensive evaluation of sural nerve specimens of CIDP patients finding a marked involvement of complement supporting the postulated concept of complement mediated demyelination in CIDP. Our results support the approach of targeting the complement system as a new and promising therapeutic strategy—at least in a subgroup of CIDP. Further research is warranted to unravel the functional implications and role of complement in CIDP progression and optimize patient care. Clinical Trial Registration: The study is registered under the German clinical trial registry (https://www.drks.de), DRKS0003245.

慢性炎性脱髓鞘性多神经病变腓肠神经的补体谱分析。
慢性炎症性脱髓鞘性多神经病变(CIDP)是一种罕见的免疫介导的多神经病变,可导致严重的残疾。虽然细胞介导和体液机制都有助于CIDP,但补体的作用仍然知之甚少。考虑到补体靶向治疗的兴起,研究补体在CIDP中的作用至关重要。在这项横断面研究中,使用组织病理学、基因和蛋白质技术分析了55名CIDP患者的腓肠神经活检,并将其与2名非患病对照组(ndc)以及8名遗传性神经病变(HN)和特发性轴突神经病变(IPN)患者进行了比较。总的来说,94% (n = 52)的患者在神经内膜毛细血管上发现了异常和显著的终末补体复合物C5b-9沉积。补体沉积明显的患者病程进展(n = 52),浸润的CD8 + T细胞和CD68 +巨噬细胞的数量和分布,因为基本的免疫学范式认为这两者可能形成免疫突触,与炎症性神经病变病因和治疗感觉和(INCAT)评分测量的临床疾病严重程度相关(p < 0.001)。此外,非靶向蛋白质组学揭示的补体蛋白丰度变化与靶向基因表达研究发现的转录水平变化一致。相比之下,NDC和DC均无补体沉积。本研究对CIDP患者的腓肠神经标本进行了广泛的评估,发现补体明显参与CIDP,支持补体介导脱髓鞘的假设概念。我们的结果支持靶向补体系统作为一种新的和有前途的治疗策略的方法-至少在CIDP的一个亚组中。进一步的研究需要揭示补体在CIDP进展中的功能含义和作用,并优化患者护理。临床试验注册:该研究在德国临床试验注册中心(https://www.drks.de)注册,DRKS0003245。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Acta Neuropathologica
Acta Neuropathologica 医学-病理学
CiteScore
23.70
自引率
3.90%
发文量
118
审稿时长
4-8 weeks
期刊介绍: Acta Neuropathologica publishes top-quality papers on the pathology of neurological diseases and experimental studies on molecular and cellular mechanisms using in vitro and in vivo models, ideally validated by analysis of human tissues. The journal accepts Original Papers, Review Articles, Case Reports, and Scientific Correspondence (Letters). Manuscripts must adhere to ethical standards, including review by appropriate ethics committees for human studies and compliance with principles of laboratory animal care for animal experiments. Failure to comply may result in rejection of the manuscript, and authors are responsible for ensuring accuracy and adherence to these requirements.
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