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The Multiple Sclerosis Performance Test MSPT: An iPad-Based Disability Assessment Tool
Published on: June 30, 2014
Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis
Jan D Lunemann1, Harald Hegen1, Luisa María Villar1
1From 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 Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain.
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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