Profiling Complement System Components in Primary CNS Vasculitis
Milani Deb-Chatterji1, Christian W Keller2, Simon Koch1
1Department of Neurology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Insights
This study found no evidence of increased complement activation in primary CNS vasculitis (PACNS) patients. Complement system proteins remained unchanged, challenging the hypothesis of systemic complement involvement in PACNS.
Area of Science:
- Immunology
- Neurology
- Rheumatology
Background:
- Complement activation is a suspected factor in vasculitic syndromes, including anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides.
- Primary central nervous system vasculitis (PACNS) is a rare condition affecting blood vessels in the brain and spinal cord.
Purpose of the Study:
- To investigate the role of complement system activation in the pathogenesis of PACNS.
- To quantify serum and cerebrospinal fluid (CSF) levels of complement proteins in PACNS patients compared to controls.
Main Methods:
- Utilized an array-based multiplex system for simultaneous quantification of complement proteins.
- Measured levels of activated complement components (C3a, C5a, SC5b-9, C4a, Ba, Bb) and regulatory proteins (factor H, factor I).
- Compared protein levels in patients with PACNS (n=20) and non-inflammatory controls (n=16).
Main Results:
- No significant differences were observed in the levels of general complement activation markers (C3a, C5a, SC5b-9).
- Specific markers for classical (C4a) and alternative (Ba, Bb) pathway activation were also unchanged.
- Concentrations of complement inhibitory proteins, factor H and factor I, were similar between PACNS patients and controls.
Conclusions:
- The study's findings do not support the hypothesis of systemically increased complement activation in patients with PACNS.
- Current evidence does not implicate the complement system as a major driver of systemic inflammation in PACNS.
Abstract:
Complement activation has been implicated in the pathogenesis of many vasculitic syndromes such as anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Using an array-based multiplex system, we simultaneously quantified serum and CSF levels of activated and regulatory complement system proteins in patients with primary CNS vasculitis (PACNS; n = 20) compared to patients with non-inflammatory conditions (n = 16). Compared to non-inflammatory controls, levels of C3a, C5a, and SC5b-9, indicative for general activation of the complement system, of C4a, specific for the activation of the classical pathway, Ba and Bb, reflective for alternative complement activation as well as concentrations of complement-inhibitory proteins factor H and factor I were unchanged in patients with PACNS. Our study does not support the hypothesis that complement activation is systemically increased in patients with PACNS.
