The Cyprus Institute of Neurology and Genetics

Author Of 1 Presentation

Biomarkers and Bioinformatics Late Breaking Abstracts

LB1276 - Contribution of antibodies against coagulation components in the circuit of coagulation-immune system: Potential biomarkers of Multiple Sclerosis? (ID 2175)

Speakers
Presentation Number
LB1276
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Coagulation components have a pivotal role to show not only as members of hemostasis system but either as regulators of innate immune response in neuroinflammatory diseases such as Multiple Sclerosis (MS). In fact, thrombin and fibrin(ogen) deposition in vasculature of the central nervous system (CNS) in MS animal models has been shown to modulate the microglia motility upon pre-demyelinated areas, to trigger and sustain inflammatory responses into perivascular lesions and, inevitably, to contribute in the axonal damage and neurodegenerative phenotype. Intriguingly, our early work has reported the presence of IgG antibodies (Abs) against coagulation components in patients with MS, albeit their role in MS pathogenesis is unknown.

Objectives

To characterize the impact of MS-derived IgG Abs against a panel of seven coagulant antigens (VIIa, thrombin, prothrombin, Xa, XII, protein C, plasmin) upon the activation of human astrocytes.

Methods

Purification of IgG Abs from 15 MS patients, who were positive for the presence of IgG against coagulation components and from 15 age and gender matched healthy donors was carried out. A human cell line of astrocytes was then treated with 100μg/ml of purified IgG for 4h and the extracted cell lysates were first quantified and then analyzed by immunoblot for the expression of the protease activator receptor -1 (PAR-1), a thrombin-activated receptor.

Results

Increased levels of PAR-1 expression were observed in astrocytes treated with IgG from MS patients who were positive for the presence of anti-thrombin and anti-plasmin IgG Abs, while not important effect was observed with IgG against other coagulant antigens of interest or with IgG derived from controls.

Conclusions

As the non-coagulation functions of thrombin are mediated by PAR-1, it is necessary to enlighten on the intracellular mechanisms that trigger the activation of PAR-1. Here, we have revealed that selective IgG Abs from MS patients can elicit the PAR-1 expression and thus may be involved in pro-inflammatory pathways that are mediated by thrombin. These findings point toward the importance of these molecules as potential biomarkers for the prognosis and/or diagnosis of MS and may prove valuable in further studies for the establishment of novel therapeutic strategies in MS.

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