| Title: |
The Role of Complement Activation in IgM M-Protein–Associated Neuropathies |
| Authors: |
van de Mortel, Johannes P. M.; Budding, Kevin; Dijkxhoorn, Kim; Minnema, Monique C.; Vrancken, Alexander F. J. E.; Notermans, Nicolette C.; van der Pol, W. Ludo; null, null; Attarian, Shahram; Basta, Ivana; van den Bergh, Peter Y. K.; Bianco, Mariangela; Briani, Chiara; Cauquil, Cécile; Carr, Aisling S.; Cornblath, David R.; Cutellè, Claudia; D'Sa, Shirley; Delmont, Emilien; van Doormaal, Perry T. C.; Doughty, Chris; Dubuisson, Nicolas; EchanizLaguna, Andoni; Elsheikh, Bakri H.; Faber, Catharina G.; Goedee, H. Stephan; Hamadeh, Tatiana; Harbo, Thomas; Hoke, Ahmet; Karlin, Lionel; Keddie, Stephen; Khoshnoodi, Mohammad; Labeyrie, Céline; Lunn, Michael P.; Marasca, Manuele; Mair, Devan; Marques, Wilson; Merkies, Ingemar S. J.; Merle, Hélène; Nascimento, Osvaldo J. M.; NobileOrazio, Eduardo; Palibrk, Aleksa; Pascual-Goñi, Elba; Peric, Stojan; Querol, Luis; Rausch, Hans-Werner; Salvalaggio, Alessandro; Schirmer, Lucas; Stino, Amro M.; Svahn, Juliette; Tejada, Clara; Thomas, Simone |
| Contributors: |
Van De Mortel, Johannes P. M.; Budding, Kevin; Dijkxhoorn, Kim; Minnema, Monique C.; Vrancken, Alexander F. J. E.; Notermans, Nicolette C.; Van Der Pol, W. Ludo; Null, Null; Attarian, Shahram; Basta, Ivana; Van Den Bergh, Peter Y. K.; Bianco, Mariangela; Briani, Chiara; Cauquil, Cécile; Carr, Aisling S.; Cornblath, David R.; Cutellè, Claudia; D'Sa, Shirley; Delmont, Emilien; Van Doormaal, Perry T. C.; Doughty, Chri; Dubuisson, Nicola; Echanizlaguna, Andoni; Elsheikh, Bakri H.; Faber, Catharina G.; Goedee, H. Stephan; Hamadeh, Tatiana; Harbo, Thoma; Hoke, Ahmet; Karlin, Lionel; Keddie, Stephen; Khoshnoodi, Mohammad; Labeyrie, Céline; Lunn, Michael P.; Marasca, Manuele; Mair, Devan; Marques, Wilson; Merkies, Ingemar S. J.; Merle, Hélène; Nascimento, Osvaldo J. M.; Nobileorazio, Eduardo; Palibrk, Aleksa; Pascual-Goñi, Elba; Peric, Stojan; Querol, Lui; Rausch, Hans-Werner; Salvalaggio, Alessandro; Schirmer, Luca; Stino, Amro M.; Svahn, Juliette; Tejada, Clara; Thomas, Simone |
| Publisher Information: |
Lippincott Williams and Wilkins |
| Publication Year: |
2024 |
| Collection: |
Padua Research Archive (IRIS - Università degli Studi di Padova) |
| Description: |
Background and ObjectivesPolyneuropathy associated with an immunoglobulin M (IgM) monoclonal gammopathy is characterized by slowly progressive, predominantly distal sensorimotor deficits, sensory ataxia, and electrophysiologic features of demyelination. IgM antibodies against myelin-Associated glycoprotein (MAG) are present in serum from most patients. Nerve damage most likely results from the concerted action of binding of anti-MAG antibodies to nerves, followed by complement activation. The interaction of anti-MAG antibodies with complement activation and their relation to clinical characteristics have not been studied in detail. We studied the correlation among anti-MAG antibody titers, complement activation, and IgM-Associated polyneuropathy disease severity.MethodsWe used serum samples from 101 patients with IgM-Associated polyneuropathy to assess IgM anti-MAG titers by ELISA and antibody-mediated complement deposition using both an ELISA-based system and a cell-based system of primate peripheral nerve slides. We studied correlations of complement activation with anti-MAG ELISA titers and clinical characteristics.ResultsIgM anti-MAG titers varied from negative to strongly positive. Complement deposition in the ELISA-based system correlated significantly with anti-MAG antibody titer (Spearman rho 0.80; p < 0.0001) despite large variability between serum samples with comparable anti-MAG titers. This variability was even larger in the cell-based assay, which also showed complement deposition in IgM anti-MAG negative patients, indicating the presence of autoantibodies directed against epitopes other than MAG in a subset of patients with IgM-Associated polyneuropathy. Clinical characteristics did not correlate with anti-MAG titers or complement activation.DiscussionAnti-MAG antibody titers correlate with the level of complement activation in both ELISA and cell-based systems. However, clinical characteristics of IgM-Associated polyneuropathy do not or only weakly correlate with titers or the level of ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/39571136; info:eu-repo/semantics/altIdentifier/wos/WOS:001363254500004; volume:12; issue:1; firstpage:e200339; lastpage:e200339(10); journal:NEUROLOGY® NEUROIMMUNOLOGY & NEUROINFLAMMATION; https://hdl.handle.net/11577/3588218 |
| DOI: |
10.1212/nxi.0000000000200339 |
| Availability: |
https://hdl.handle.net/11577/3588218; https://doi.org/10.1212/nxi.0000000000200339 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.B25E263F |
| Database: |
BASE |