Antibodies to blood coagulation components are implicated in patients with multiple sclerosis

Abstract

Background: The strong link between innate immunity and thrombosis/coagulation has recently been investigated in the light of antibodies directed against serine proteases of the coagulation pathway. The antibodies have been proposed as contributing factors to venous thromboembolism development and as key molecules in the initiation of signaling inflammatory pathways in neuroinflammatory diseases. Preliminary studies of Multiple Sclerosis (MS) progression characteristics with the reactivity of antibodies against coagulant components are limited. Considering the development of thrombosis at the early onset of MS, our study aimed to detect antibodies against coagulant components in MS and evaluate their possible association with the clinical profile of the disease.

Method: A cross-sectional study was carried out to identify antibodies to factor(F)VIIa, thrombin, prothrombin, FXa, FXII, plasmin, and protein C in serum samples from 167 patients with MS and 40 healthy controls using the enzyme-linked immunosorbent assay. Statistical analysis was performed for the evaluation of the data.

Results: The analysis revealed a significantly higher prevalence of IgG in MS patients (n = 72, 43%) compared to HCs (n = 8, 20%, p < 0.01). Specifically, elevated anti-FVIIa (n = 19, 11.4%, mean activity p < 0.0001), anti-FXII (n = 12, 7.2%, mean activity p < 0.001) and anti-plasmin (n = 20, 12%, mean activity p < 0.01) levels were observed in patients compared to controls. Additionally, the highest scores of clinical characteristics like the expanded disability status scale and MS severity score were linked with IgG seropositivity against thrombin, whilst anti-FXII levels corresponded with the lowest disease progression.

Conclusion: The findings of our study illustrate the presence of antibodies against serine proteases of the coagulation cascade in MS and demonstrate the association of antibody activity with disease progression. In particular, thrombin IgG seropositivity was demonstrated to be associated with worse outcomes and a severe disease phenotype. These observations suggest the implication of antibodies in patient monitoring and prognosis, and further evaluation may elucidate inflammatory cascades in which antibodies act as key mediators.

Keywords: Antibodies; Coagulant factors; Multiple sclerosis; Multiple sclerosis severity score; Thrombosis.