Mechanisms of activation induced by antiphospholipid antibodies in multiple sclerosis: Potential biomarkers of disease?

Abstract

Multiple sclerosis (MS) is a chronic, multifactorial, inflammatory disease of the central nervous system where demyelination leads to neurodegeneration and disability. The pathogenesis of MS is incompletely understood, with prevalence of antiphospholipid antibodies (aPL) speculated to contribute to MS pathogenesis. In fact, MS shares common clinical features with the Antiphospholipid Syndrome (APS) such as venous thromboembolism. Consequently, the presence of aPL which are associated with blood clot formation in the APS need to be further investigated for a possible pro-coagulant role in the development of thrombosis in MS. The effects of IgG aPL from patients with MS upon astrocyte activation has never been characterized. We purified IgG from 30 subjects. A human astrocytic cell line was treated with 100 μg/ml IgG for 1 h, and cell extracts were examined by immunoblot using antibodies to p38 MAPK and NFκB to further examine intracellular signaling pathways induced by these IgGs. Only IgG from patients who are positive for aPL caused phosphorylation of p38 MAPK and NFκB in astrocytes. These effects were not seen with IgG from patients with MS but with no aPL or healthy controls. Understanding the intracellular mechanism of aPL-mediated astrocyte activation may help to establish new therapeutic approaches, such as selective inhibition of the mitogen-activated protein kinases, to control MS activity or possible thrombotic states.