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
{"title":"Complement profiling of sural nerves in chronic-inflammatory demyelinating polyneuropathy","authors":"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","doi":"10.1007/s00401-025-02936-w","DOIUrl":null,"url":null,"abstract":"<div><p>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 (<i>p</i> < 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. <i>Clinical Trial Registration</i>: The study is registered under the German clinical trial registry (https://www.drks.de), DRKS0003245.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"150 1","pages":""},"PeriodicalIF":9.3000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00401-025-02936-w.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Neuropathologica","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s00401-025-02936-w","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
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.
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.