Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis
The 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). Sixty-eight pati...
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Published in: | Neurology : neuroimmunology & neuroinflammation Vol. 11; no. 4; p. e200270 |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
United States
Lippincott Williams & Wilkins
01-07-2024
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Subjects: | |
Online Access: | Get full text |
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Summary: | The 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).
Sixty-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).
In 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;
= 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;
= 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;
= 0.037), and increased CSF C1q levels predicted lower disability progression (adjusted OR 0.41; 95% CI 0.17-0.86;
= 0.025).
Proteins 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work and are therefore designated as last coauthors. Submitted and externally peer reviewed. The handling editor was Associate Editor Friedemann Paul, MD. Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article. |
ISSN: | 2332-7812 2332-7812 |
DOI: | 10.1212/NXI.0000000000200270 |