HMGB1 as a potential new marker of disease activity in patients with multiple sclerosis
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ORIGINAL ARTICLE
HMGB1 as a potential new marker of disease activity in patients with multiple sclerosis Maria Bucova 1 & Beata Majernikova 1 & Vladimira Durmanova 1 & Daniela Cudrakova 2 & Karin Gmitterova 3 & Iveta Lisa 3 & Eleonora Klimova 4 & Kristina Kluckova 1 & Milan Buc 1 Received: 27 August 2019 / Accepted: 31 October 2019 # Fondazione Società Italiana di Neurologia 2019
Abstract Objectives Neuroinflammation represents one of the two major pathological components of multiple sclerosis (MS). The aim of our study was to find the role of the late pro-inflammatory cytokine HMGB1 (high mobility group box) in MS pathogenesis. Subjects and methods A total of 165 patients from three MS centers in Slovakia were enrolled in the study. Patients underwent a complex clinical investigation and their plasma levels of HMGB1 were analyzed by a sandwich ELISA test. Results MS patients had 4.5 times higher plasma level of HMGB1 (median, 13.529 ng/mL; IQR = 2.330-113.45) than healthy controls (median, 2.999 ng/mL; IQR = 1.686-9.844; P < 0.0001). The concentrations of HMGB1 were significantly associated with increased number of affected areas diagnosed by MRI (P < 0.0001) (the median for one affected area, 4.205 ng/mL; median for five affected areas, 17.843 ng/mL; P < 0.05). Patients with at least one active lesion in any of the affected areas in the brain had significantly higher plasma levels of HMGB1 (median, 20.118 ng/mL; IQR, 3.693–100.12) than those without any active lesion (median, 16.695 ng/mL; IQR, 3.255–113.45; P < 0.0235). We found also a very highly significant association of HMGB1 plasma levels with clinical condition expressed as EDSS (expanded disability status scale) (P < 0.0001); patients with higher EDSS had higher levels of HMGB1 (EDSS ≤ 2.5, 11.648 ng/mL vs. EDSS ≥ 3, 17.549 ng/mL; P = 0.0115). Conclusion Our results suggest chronic low-grade inflammation in MS patients that correlates with clinical conditions of MS patients, and for HMGB1 as a possible target molecule in future therapy. Keywords HMGB1 . Immunity . Inflammation . Multiple sclerosis . EDSS . MSSS
Introduction Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease with unresolved multifactorial etiology. Mostly, young adults between 20 and 40 years are affected and women are affected twice as often as men [1, 2]. The cause of MS is still
* Maria Bucova [email protected]; [email protected] 1
Institute of Immunology, Faculty of Medicine, Comenius University, Spitalska 24, 813 72 Bratislava, Slovakia
2
1st. Department of Neurology, Faculty of Medicine, Comenius University and University Hospital, Bratislava, Slovakia
3
2nd Department of Neurology, Faculty of Medicine, Comenius University, Bratislava, Slovakia
4
Centre for Therapy and Diagnosis of Multiple Sclerosis, Faculty Hospital of JA Raiman, Presov, Slovakia
unknown, but it is undeniable that besides genetic background, stress, and environmental factors, the immune abnormalities play a role in MS development. Multifocal areas with focal lympho
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