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

BACKGROUND: 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. METHODS: HMGB1 mRNA exp...

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Detalles Bibliográficos
Autores principales: Malhotra, Sunny, Fissolo, Nicolas, Tintoré, Mar, Wing, Ana Cristina, Castilló, Joaquin, Vidal-Jordana, Angela, Montalban, Xavier, Comabella, Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359557/
https://www.ncbi.nlm.nih.gov/pubmed/25879961
http://dx.doi.org/10.1186/s12974-015-0269-9
Descripción
Sumario:BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0269-9) contains supplementary material, which is available to authorized users.