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Evaluation of the coagulation dysfunction in Multiple Sclerosis from the perspective of IgG antibodies against thrombus-related components
* 1 , 2 , 2 , 1 , 1
1  Department of Neuroimmunology, The Cyprus Institute of Neurology and Genetics
2  Department of Molecular Virology, The Cyprus Institute of Neurology and Genetics
Academic Editor: Jitka Petrlova


The strong link between coagulation and inflammation has recently been investigated in multiple sclerosis (MS) in the light of coagulant serine proteases as potential pro-inflammatory mediators in the central nervous system of MS animal models. Furthermore, antibodies against coagulant components have been suggested as pro-coagulant effectors, suppressing anticoagulant mechanisms and enhancing thrombosis in diseases with clinical features similar to those of MS. Our research attempted to investigate the effects of IgG antibodies in the coagulation-inflammation circuit and characterize their role in MS pathology. Serum samples from 15 seropositive MS patients for IgG antibodies against factor (F)VIIa, thrombin, prothrombin, FXa, FXII, plasmin, and protein C were subjected to antibody purification by affinity chromatography, followed by in vitro stimulation of human astrocytes. Serum samples from 14 healthy controls and 8 negative MS patients for antibodies studied were also subjected to the same procedure to be used as negative controls. The expression levels of the thrombin-activated receptor (PAR-1) and activated pro-inflammatory ERK1/2 kinases were analyzed by immunoblot to evaluate intracellular signaling pathways triggered by these antibodies. Using human primary astrocytes, we validated our results ex vivo. The highest expression levels of pro-inflammatory molecules were observed when fractions with anti-thrombin IgG or fractions with cross-reactivities were used for stimulation. Namely, we observed upregulation of the PAR-1 receptor up to four-fold compared to unstimulated astrocytes and up to 2.5-fold overexpression of the activated ERK1/2 kinases following astrocytic stimulation with purified IgG from seropositive MS patients. Conversely, no substantial alteration was observed when purified samples from MS patients who tested negative for IgG and healthy controls were used upon stimulation. Therefore, understanding the role of IgG against coagulation components in intracellular signaling pathways involved in MS may serve as biomarkers for prognosis and monitoring of disease and may prove valuable in establishing novel therapeutic strategies.

Keywords: Multiple sclerosis; coagulation; inflammation; antibodies; intracellular pathways