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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.
Complement proteins influence multiple sclerosis (MS) progression. Elevated serum C3a/C3 ratio indicates higher risk, while increased cerebrospinal fluid C1q suggests a protective effect in primary progressive MS (PPMS).
Area of Science:
- Neuroimmunology
- Complement system biology
- Clinical neurology
Background:
- The complement system's role in multiple sclerosis (MS) pathogenesis is recognized, but its specific contribution to disease progression, particularly in primary progressive MS (PPMS), remains unclear.
- Understanding these mechanisms is crucial for developing targeted therapies for MS progression.
Purpose of the Study:
- To investigate the association between complement component (CC) levels and disability progression in patients with primary progressive multiple sclerosis (PPMS).
- To identify specific complement factors that may act as risk or protective elements in long-term MS disability.
Main Methods:
- Serum and cerebrospinal fluid (CSF) levels of complement components were measured in 68 PPMS patients from 12 European centers.
- Longitudinal follow-up averaged 9.6 years, with statistical analyses (logistic regression) adjusted for age, sex, and albumin quotient.
- Associations between baseline CC levels and disability progression were assessed at short-term (2 years), medium-term (6 years), and long-term (final follow-up).
Main Results:
- In the short term, complement components showed minimal impact on disability progression.
- By medium and long term, an elevated serum C3a/C3 ratio was significantly associated with a higher risk of disability progression (ORs ranging from 1.81 to 2.30).
- Conversely, increased CSF C1q levels were linked to a trend toward reduced disability progression in the medium term and a significant protective effect in the long term (ORs around 0.41-0.43).
Conclusions:
- Proteins in early complement cascade activation, specifically serum C3a/C3 ratio and CSF C1q, act as significant risk and protective factors, respectively, for disability progression in PPMS after six or more years.
- The neuroprotective and anti-inflammatory properties of C1q in the CSF may underlie its observed protective effects against MS progression.
- These findings highlight the complex role of the complement system in MS and suggest potential therapeutic targets for managing disease progression.
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