Cypriot researchers from the Cyprus Institute of Neurology and Genetics (CING), have made a new discovery on Multiple Sclerosis contributing to the identification of new biomarkers and evaluated their effect on the clinical picture of patients.
The research team of CING included Senior Consultant Neurologist, Head of Neurology Clinic C, Professor, The Cyprus School of Molecular Medicine Dr. Marios Pantzaris, Dr. Anastasia Lambrianides and Maria S. Hadjiagapiou, PhD Candidate, in collaboration with the Department of Molecular Virology, led by Professor Christina Christodoulou.
In the current study, 167 participants diagnosed with MS at the Neuroimmunology Department of the Cyprus Institute of Neurology and Genetics were enrolled during routine follow-up appointments between September 2017 and January 2019. Out of 167 patients with MS, 130 had Relapsing-Remitting MS (RRMS), 29 Secondary Progressive MS (SPMS) and seven Primary Progressive MS (PPMS) and one participant was diagnosed with clinically isolated syndrome (CIS).
It was funded by the TELETHON programme and the results were published in the international scientific journal Multiple Sclerosis and Related Disorders.
As the study notes, Multiple Sclerosis is a heterogeneous and multifactorial disease of the central nervous system (CNS), characterized by multifocal plaque formation within the CNS and the disruption of self-immune tolerance, thereby promoting a neurodegenerative and autoimmune phenotype.
Despite the in-depth research that has been conducted up to date, the etiology of MS is still elusive and no study has shed light on the development and progression of the disease. In addition, there are no previous studies to evaluate the relationship between antibodies against coagulant components and MS progression. To this date, numerous studies have investigated the above hypothesis in antiphospholipid syndrome (APS), but since both diseases share common clinical features, this should be investigated further in MS.
Therefore, the purpose of the study was to detect the seroprevalence of antibodies against procoagulant, anticoagulant, and fibrinolytic molecules in patients with MS and to determine whether these antibodies contribute to the progression and disability of the disease.
The presence of immunoglobulin G against serine proteases of the coagulation cascade was analyzed in patients with MS to test the team’s hypothesis that such antibodies might contribute to MS progression. A total of 43% showed significantly higher levels of IgG for at least one antibody. Furthermore, the findings indicated that patients had significantly elevated levels of binding activity to FVIIa, FXII and plasmin than healthy individuals. Noteworthy, the anti-FVIIa antibody was found to be an important marker for patients suffering from RRMS and SPMS in the study since the binding activity levels were significantly elevated in these groups. Moreover, the levels of anti-FXII could also differentiate RRMS patients from HCs, while patients with SPMS differed significantly from HCs in binding activity to plasmin. This observation was further extended with the correlation between anti-plasmin and EDSS as well as between anti-plasmin and age, demonstrating the implication of such antibodies in disease disability over time.
The findings of the 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.
Overall, the IgG antibodies directed against serine proteases of the coagulation cascade illustrated an increased prevalence in patients with MS. Moreover, clinical features of the disease can also be associated with the presence of particular IgG antibodies against the coagulation serine proteases. Further studies are needed, the study suggests, to evaluate these molecules as part of the coagulation-inflammation circuit and their clinical significance in MS progression to assess whether they can contribute to better monitoring and prognosis of the disease as well as whether they can serve as targets for novel therapeutic strategies.
Source: Cyprus News Agency