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Title: | Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis |
Author: | Lunemann, Jan D. Hegen, Harald Villar, Luisa María Rejdak, Konrad Sao-aviles, Augusto Carbonell-mirabent, Pere Sastre-garriga, Jaume Mongay-ochoa, Neus Berek, Klaus Martínez-yélamos, Sergio Pérez-miralles, Francisco Abdelhak, Ahmed Bachhuber, Franziska Tumani, Hayrettin Lycke, Jan N. Rosenstein, Igal Alvarez-lafuente, Roberto Castillo-trivino, Tamara Otaegui, David Llufriu, Sara Blanco, Yolanda Sánchez López, Antonio J. Garcia Merino, Juan Antonio Fissolo, Nicolas Gutierrez, Lucia Villacieros-Álvarez, Javier Monreal, Enric Valls-carbó, Adrián Wiendl, Heinz Montalban, Xavier Comabella, Manuel |
Issue Date: | 1-Jul-2024 |
Publisher: | Ovid Technologies (Wolters Kluwer Health) |
Abstract: | Background and ObjectivesThe complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS).MethodsSixty-eight patients with PPMS from 12 European MS centers were included in the study. Serum and CSF levels of a panel of complement components (CCs) were measured by multiplex enzyme-linked immunosorbent assay at a baseline time point (i.e., sampling). Mean (SD) follow-up time from baseline was 9.6 (4.8) years. Only one patient (1.5%) was treated during follow-up. Univariable and multivariable logistic regressions adjusted for age, sex, and albumin quotient were performed to assess the association between baseline CC levels and disability progression in short term (2 years), medium term (6 years), and long term (at the time of the last follow-up).ResultsIn short term, CC played little or no role in disability progression. In medium term, an elevated serum C3a/C3 ratio was associated with a higher risk of disability progression (adjusted OR 2.30; 95% CI 1.17-6.03; p = 0.040). By contrast, increased CSF C1q levels were associated with a trend toward reduced risk of disability progression (adjusted OR 0.43; 95% CI 0.17-0.98; p = 0.054). Similarly, in long term, an elevated serum C3a/C3 ratio was associated with higher risk of disability progression (adjusted OR 1.81; 95% CI 1.09-3.40; p = 0.037), and increased CSF C1q levels predicted lower disability progression (adjusted OR 0.41; 95% CI 0.17-0.86; p = 0.025).DiscussionProteins involved in the activation of early complement cascades play a role in disability progression as risk (elevated serum C3a/C3 ratio) or protective (elevated CSF C1q) factors after 6 or more years of follow-up in patients with PPMS. The protective effects associated with C1q levels in CSF may be related to its neuroprotective and anti-inflammatory properties. |
Note: | Reproducció del document publicat a: https://doi.org/10.1212/NXI.0000000000200270 |
It is part of: | Neurology Neuroimmunology & Neuroinflammation, 2024, vol. 11, issue. 4 |
URI: | http://hdl.handle.net/2445/216161 |
Related resource: | https://doi.org/10.1212/NXI.0000000000200270 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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