Role of high mobility group box protein 1 (HMGB1) in peripheral blood from patients with multiple sclerosis

Altres ajuts: The authors thank the 'Red Española de Esclerosis Múltiple (REEM)' sponsored by the 'Fondo de Investigación Sanitaria' (FIS), Ministry of Science and Innovation, Spain, and the 'Ajuts per donar Suport als Grups de Recerca de Catalunya,' sponsored by the 'Agència de Gestió d'Ajuts Universitaris i de Recerca' (AGAUR), Generalitat de Catalunya, Spain.High mobility group box protein 1 (HMGB1) is a transcriptional regulator that is receiving increasing attention in autoimmune disorders including multiple sclerosis (MS). Here, we investigated the role of HMGB1 in the peripheral blood compartment from MS patients. HMGB1 mRNA expression levels were determined by PCR in peripheral blood mononuclear cells (PBMC) of 29 healthy controls and 57 untreated MS patients (26 with relapsing-remitting MS - RRMS, 13 with secondary progressive MS - SPMS, and 18 with primary progressive MS - PPMS). HMGB1 protein levels were measured by ELISA in serum samples from 18 HC and 37 untreated MS patients (13 with RRMS, 14 with SPMS, and 10 with PPMS). HMGB1 expression levels were increased in PBMC from the whole MS group compared with controls (P = 0.03). Further stratification of the MS group revealed higher expression levels in PBMC from patients with relapse-onset MS, and differences were statistically significant for RRMS patients compared with PPMS patients and controls (P = 4 × 10 −5 and P = 0.005, respectively) and also for SPMS patients compared with PPMS patients (P = 0.001). HMGB1 serum levels were increased in the whole MS group compared with controls (P = 2 × 10 −4). In MS clinical forms, the highest HMGB1 serum levels were observed in RRMS patients, and differences were statistically significant compared to PPMS patients (P = 5 × 10 −5), SPMS patients (P = 0.001), and controls (P = 0.001). These results point to a role of HMGB1 mRNA and protein levels as disease activity biomarkers to discriminate the more inflammatory relapse-onset MS forms, particularly RRMS, from the less inflammatory PPMS form of the disease. The online version of this article (doi:10.1186/s12974-015-0269-9) contains supplementary material, which is available to authorized users

MRI phenotypes with high neurodegeneration are associated with peripheral blood B-cell changes

Postprint (author's final draft

Optic Nerve Topography in Multiple Sclerosis Diagnosis

To assess the added value of the optic nerve region (by using visual evoked potentials [VEPs]) to the current diagnostic criteria. From the Barcelona clinically isolated syndrome (CIS) cohort, patients with complete information to assess dissemination in space (DIS), the optic nerve region, and dissemination in time at baseline (n = 388) were selected. Modified DIS (modDIS) criteria were constructed by adding the optic nerve to the current DIS regions. The DIS and modDIS criteria were evaluated with univariable Cox proportional hazard regression analyses with the time to the second attack as the outcome. A subset of these patients who had at least 10 years of follow-up or a second attack occurring within 10 years (n = 151) were selected to assess the diagnostic performance. The analyses were also performed according to CIS topography (optic neuritis vs non-optic neuritis). The addition of the optic nerve as a fifth region improved the diagnostic performance by slightly increasing the accuracy (2017 DIS 75.5%, modDIS 78.1%) and the sensitivity (2017 DIS 79.2%, modDIS 82.3%) without lowering the specificity (2017 DIS 52.4%, modDIS 52.4%). When the analysis was conducted according to CIS topography, the modDIS criteria performed similarly in both optic neuritis and non-optic neuritis CIS. The addition of the optic nerve, assessed by VEP, as a fifth region in the current DIS criteria slightly improves the diagnostic performance because it increases sensitivity without losing specificity

The long-term outcomes of CIS patients in the Barcelona inception cohort : Looking back to recognize aggressive MS

Altres ajuts: This study has been funded by European Regional Development Fund and co-funded by Instituto Carlos III. It has also received support by a grant from Genzyme foundation (GENZYME-2015-01) granted to M.T. and from the 'Red Española de Esclerosis Múltiple (REEM)', which is sponsored by FIS, the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness in Spain, and the 'Ajuts per donar Suport als Grups de Recerca de Catalunya', which is sponsored by the 'Agència de Gestió d'Ajuts Universitaris i de Recerca' (AGAUR) of the Generalitat de Catalunya in Spain.To explore the long-term outcomes of patients with clinically isolated syndromes from the Barcelona cohort. We selected patients with a follow-up longer than 10 years to (1) estimate the risks of multiple sclerosis (MS) and disability accumulation according to the baseline number of T2 lesions and to compare treated versus untreated patients and early versus delayed treatment, and (2) to study baseline features of patients with aggressive MS (Expanded Disability Status Scale (EDSS) ⩾6.0 at 10 years). In all, 401 patients were included (mean follow-up of 14.4 (standard deviation of 2.9) years). A higher number of T2 lesions was associated with an earlier MS diagnosis and an earlier risk of irreversible disability. Early treatment was associated with a decreased risk of EDSS of 3.0: adjusted hazard ratio = 0.4, 95% confidence interval = (0.2, 0.7). Patients with aggressive MS differed in their baseline brain magnetic resonance images: The median (interquartile range) number of T2 lesions and contrast-enhancing lesions (CEL) was 71 (28-95) versus 7 (1-19) and 3 (1-24) versus 0 (0-1), respectively. The cut-offs that better classified patients with aggressive MS were 20 for T2 lesions and 2 for CEL. Although MS natural history is changing, a high lesion load at onset is helpful to identify patients at risk of presenting an aggressive MS

The long-term outcomes of CIS patients in the Barcelona inception cohort : Looking back to recognize aggressive MS

Altres ajuts: This study has been funded by European Regional Development Fund and co-funded by Instituto Carlos III. It has also received support by a grant from Genzyme foundation (GENZYME-2015-01) granted to M.T. and from the 'Red Española de Esclerosis Múltiple (REEM)', which is sponsored by FIS, the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness in Spain, and the 'Ajuts per donar Suport als Grups de Recerca de Catalunya', which is sponsored by the 'Agència de Gestió d'Ajuts Universitaris i de Recerca' (AGAUR) of the Generalitat de Catalunya in Spain.To explore the long-term outcomes of patients with clinically isolated syndromes from the Barcelona cohort. We selected patients with a follow-up longer than 10 years to (1) estimate the risks of multiple sclerosis (MS) and disability accumulation according to the baseline number of T2 lesions and to compare treated versus untreated patients and early versus delayed treatment, and (2) to study baseline features of patients with aggressive MS (Expanded Disability Status Scale (EDSS) ⩾6.0 at 10 years). In all, 401 patients were included (mean follow-up of 14.4 (standard deviation of 2.9) years). A higher number of T2 lesions was associated with an earlier MS diagnosis and an earlier risk of irreversible disability. Early treatment was associated with a decreased risk of EDSS of 3.0: adjusted hazard ratio = 0.4, 95% confidence interval = (0.2, 0.7). Patients with aggressive MS differed in their baseline brain magnetic resonance images: The median (interquartile range) number of T2 lesions and contrast-enhancing lesions (CEL) was 71 (28-95) versus 7 (1-19) and 3 (1-24) versus 0 (0-1), respectively. The cut-offs that better classified patients with aggressive MS were 20 for T2 lesions and 2 for CEL. Although MS natural history is changing, a high lesion load at onset is helpful to identify patients at risk of presenting an aggressive MS