Evaluation of the Coagulation Dysfunction in Multiple Sclerosis from the Perspective of IgG Antibodies against Thrombus-Related Components

Abstract

The strong link between coagulation and inflammation has recently been investigated in multiple sclerosis (MS) in the light of coagulant serine proteases as pro-inflammatory mediators in MS animal models. Our work attempted to enlighten the role of IgG antibodies against the coagulant proteases and characterize their effects in MS pathology. Serum samples from 15 seropositive MS patients for IgG against factor(F)VIIa, thrombin, prothrombin, FXa, FXII, plasmin, and protein C were subjected to antibody purification, followed by in vitro stimulation of human astrocytes. Samples from fourteen healthy controls and eight negative MS patients for antibodies were also subjected to the same procedure 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 pathways triggered by these antibodies. PAR-1 and ERK1/2 were upregulated up to four-fold and 2.5-fold, respectively, after stimulation with anti-thrombin IgG fraction or fractions with multiple antibodies, compared to untreated cells. Conversely, no substantial alteration was observed when samples from negative patients for IgG and controls were applied. Thus, IgG against coagulation components might be pro-inflammatory molecules useful for prognosis, monitoring, and developing new therapeutic approaches for MS.

Keywords

• multiple sclerosis
• inflammation
• coagulation
• antibodies
• inflammatory signaling pathways