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Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis.
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.
Afiliación
  • Lunemann JD; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Hegen H; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Villar LM; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Rejdak K; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Sao-Aviles A; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Carbonell-Mirabent P; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Sastre-Garriga J; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Mongay-Ochoa N; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Berek K; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Martínez-Yélamos S; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Pérez-Miralles F; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Abdelhak A; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Bachhuber F; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Tumani H; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Lycke JN; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Rosenstein I; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Alvarez-Lafuente R; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Castillo-Trivino T; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Otaegui D; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Llufriu S; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Blanco Y; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Sánchez López AJ; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Garcia Merino JA; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Fissolo N; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Gutierrez L; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Villacieros-Álvarez J; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Monreal E; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Valls-Carbó A; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Wiendl H; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Montalban X; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
  • Comabella M; From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ra
Neurol Neuroimmunol Neuroinflamm ; 11(4): e200270, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38912898
ABSTRACT
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.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Progresión de la Enfermedad / Esclerosis Múltiple Crónica Progresiva Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Neurol Neuroimmunol Neuroinflamm Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Progresión de la Enfermedad / Esclerosis Múltiple Crónica Progresiva Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Neurol Neuroimmunol Neuroinflamm Año: 2024 Tipo del documento: Article