Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke
1 3rd Department of Internal Medicine, Semmelwies University, Budapest, Hungary
2 Laboratory of Molecular Medicine, Department of Clinical Immunology-7631, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
3 Division of Clinical and Experimental Neuroimmunology, Department of Neurology, University of Pecs, Pecs, Hungary
4 Institute of Anaesthesia and Intensive Therapy, Faculty of Medicine, University of Pecs, Pecs, Hungary
5 Heart Center, Semmelweis University, Budapest, Hungary
6 Department of Neurology, Kútvölgyi Clinical Centre, Semmelweis University, Budapest, Hungary
7 Experimental Laboratory of Cardiac Surgery, University of Heidelberg, Germany
Journal of Neuroinflammation 2011, 8:185 doi:10.1186/1742-2094-8-185Published: 29 December 2011
A number of data indicate that the lectin pathway of complement activation contributes to the pathophysiology of ischemic stroke. The lectin pathway may be triggered by the binding of mannose-binding lectin (MBL), ficolin-2 or ficolin-3 to different ligands. Although several papers demonstrated the significance of MBL in ischemic stroke, the role of ficolins has not been examined.
Sera were obtained within 12 hours after the onset of ischemic stroke (admission samples) and 3-4 days later (follow-up samples) from 65 patients. The control group comprised 100 healthy individuals and 135 patients with significant carotid stenosis (patient controls). The concentrations of ficolin-2 and ficolin-3, initiator molecules of the lectin complement pathway, were measured by ELISA methods. Concentration of C-reactive protein (CRP) was also determined by a particle-enhanced immunturbidimetric assay.
Concentrations of both ficolin-2 and ficolin-3 were significantly (p < 0.001) decreased in both the admission and in the follow-up samples of patients with definite ischemic stroke as compared to healthy subjects. Concentrations of ficolin-2 and ficolin-3 were even higher in patient controls than in healthy subjects, indicating that the decreased levels in sera during the acute phase of stroke are related to the acute ischemic event. Ficolin-3 levels in the follow-up samples inversely correlated with the severity of stroke indicated by NIH scale on admission. In follow-up samples an inverse correlation was observed between ficolin-3 levels and concentration of S100β, an indicator of the size of cerebral infarct. Patients with low ficolin-3 levels and high CRP levels in the follow up samples had a significantly worse outcome (adjusted ORs 5.6 and 3.9, respectively) as measured by the modified Rankin scale compared to patients with higher ficolin-3 and lower CRP concentrations. High CRP concentrations were similarly predictive for worse outcome, and the effects of low ficolin-3 and high CRP were independent.
Our findings indicate that ficolin-mediated lectin pathways of complement activation contribute to the pathogenesis of ischemic stroke and may be additive to complement-independent inflammatory processes.