Maria Bucova1, Beata Majernikova2, Vladimira Durmanova2, Daniela Cudrakova3, Karin Gmitterova4, Iveta Lisa4, Eleonora Klimova5, Kristina Kluckova2, Milan Buc2. 1. Institute of Immunology, Faculty of Medicine, Comenius University, Spitalska 24, 813 72, Bratislava, Slovakia. maria.bucova@fmed.uniba.sk. 2. Institute of Immunology, Faculty of Medicine, Comenius University, Spitalska 24, 813 72, Bratislava, Slovakia. 3. 1st. Department of Neurology, Faculty of Medicine, Comenius University and University Hospital, Bratislava, Slovakia. 4. 2nd Department of Neurology, Faculty of Medicine, Comenius University, Bratislava, Slovakia. 5. Centre for Therapy and Diagnosis of Multiple Sclerosis, Faculty Hospital of JA Raiman, Presov, Slovakia.
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.
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:MSpatients 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 MSpatients that correlates with clinical conditions of MSpatients, and for HMGB1 as a possible target molecule in future therapy.
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