TY - JOUR
T1 - Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis
AU - Lunemann, Jan D
AU - Hegen, Harald
AU - Villar, Luisa María
AU - Rejdak, Konrad
AU - Sao-Aviles, Augusto
AU - Carbonell-Mirabent, Pere
AU - Sastre-Garriga, Jaume
AU - Mongay-Ochoa, Neus
AU - Berek, Klaus
AU - Martínez-Yélamos, Sergio
AU - Pérez-Miralles, Francisco
AU - Abdelhak, Ahmed
AU - Bachhuber, Franziska
AU - Tumani, Hayrettin
AU - Lycke, Jan N
AU - Rosenstein, Igal
AU - Alvarez-Lafuente, Roberto
AU - Castillo-Trivino, Tamara
AU - Otaegui, David
AU - Llufriu, Sara
AU - Blanco, Yolanda
AU - Sánchez López, Antonio J
AU - Garcia Merino, Juan Antonio
AU - Fissolo, Nicolas
AU - Gutierrez, Lucia
AU - Villacieros-Álvarez, Javier
AU - Monreal, Enric
AU - Valls-Carbó, Adrián
AU - Wiendl, Heinz
AU - Montalban, Xavier
AU - Comabella, Manuel
N1 - Publisher Copyright:
© American Academy of Neurology.
PY - 2024/7
Y1 - 2024/7
N2 - BACKGROUND AND OBJECTIVES: 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).METHODS: 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).RESULTS: 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; 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). DISCUSSION: 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.
AB - BACKGROUND AND OBJECTIVES: 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).METHODS: 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).RESULTS: 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; 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). DISCUSSION: 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.
KW - Activation
KW - Biomarker
KW - C1q
KW - Cerebrospinal-fluid
KW - Disease
KW - Immunology
KW - Meningeal inflammation
KW - Regulator factor-h
KW - System
KW - Terminal complement
UR - https://www.mendeley.com/catalogue/49e84ddb-c5f6-38f9-a2c8-ff9d96e85594/
UR - http://www.scopus.com/inward/record.url?scp=85196979919&partnerID=8YFLogxK
U2 - 10.1212/NXI.0000000000200270
DO - 10.1212/NXI.0000000000200270
M3 - Article
C2 - 38912898
SN - 2332-7812
VL - 11
SP - e200270
JO - Neurology(R) neuroimmunology & neuroinflammation
JF - Neurology(R) neuroimmunology & neuroinflammation
IS - 4
M1 - e200270
ER -