The complement system as a biomarker of disease activity and response to treatment in multiple sclerosis

Immunol Res. 2017 Dec;65(6):1103-1109. doi: 10.1007/s12026-017-8961-8.


Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. The complement system has an established role in the pathogenesis of MS, and evidence suggests that its components can be used as biomarkers of disease-state activity and response to treatment in MS. Plasma C4a levels have been found to be significantly elevated in patients with active relapsing-remitting MS (RRMS), as compared to both controls and patients with stable RRMS. C3 levels are also significantly elevated in the cerebrospinal fluid (CSF) of patients with RRMS, and C3 levels are correlated with clinical disability. Furthermore, increased levels of factor H can predict the transition from relapsing to progressive disease, since factor H levels have been found to increase progressively with disease progression over a 2-year period in patients transitioning from RRMS to secondary progressive (SP) MS. In addition, elevations in C3 are seen in primary progressive (PP) MS. Complement components can also differentiate RRMS from neuromyelitis optica. Response gene to complement (RGC)-32, a novel molecule induced by complement activation, is a possible biomarker of relapse and response to glatiramer acetate (GA) therapy, since RGC-32 mRNA expression is significantly decreased during relapse and increased in responders to GA treatment. The predictive accuracy of RGC-32 as a potential biomarker (by ROC analysis) is 90% for detecting relapses and 85% for detecting a response to GA treatment. Thus, complement components can serve as biomarkers of disease activity to differentiate MS subtypes and to measure response to therapy.

Keywords: Biomarker; Complement activation; Factor H; Glatiramer acetate; Multiple sclerosis; RGC-32.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Pharmacological / blood
  • Biomarkers, Pharmacological / metabolism*
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Complement System Proteins / metabolism
  • Diagnosis, Differential
  • Disease Progression
  • Glatiramer Acetate / therapeutic use*
  • Humans
  • Multiple Sclerosis / diagnosis*
  • Multiple Sclerosis / drug therapy
  • Muscle Proteins / genetics*
  • Muscle Proteins / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neuromyelitis Optica / diagnosis*


  • Biomarkers, Pharmacological
  • Cell Cycle Proteins
  • Muscle Proteins
  • Nerve Tissue Proteins
  • RGCC protein, human
  • Glatiramer Acetate
  • Complement System Proteins