Format

Send to

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

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

Author information

1
Department of Neurology, University of Maryland, School of Medicine, 655 W Baltimore St, BRB 12-033, Baltimore, MD, 21201, USA.
2
Department of Rheumatology, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
3
Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland, School of Medicine, Baltimore, MD, USA.
4
Department of Neurology, University of Maryland, School of Medicine, 655 W Baltimore St, BRB 12-033, Baltimore, MD, 21201, USA. hrus@umaryland.edu.
5
Research Service, Veterans Administration Maryland Health Care System, Baltimore, MD, USA. hrus@umaryland.edu.
6
Veterans Administration Multiple Sclerosis Center of Excellence-East, Baltimore, MD, USA. hrus@umaryland.edu.

Abstract

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

PMID:
29116612
DOI:
10.1007/s12026-017-8961-8
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center