Skip to main content
Top
Published in: Journal of Neuroinflammation 1/2015

Open Access 01-12-2015 | Short report

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

Authors: Sunny Malhotra, Nicolas Fissolo, Mar Tintoré, Ana Cristina Wing, Joaquin Castilló, Angela Vidal-Jordana, Xavier Montalban, Manuel Comabella

Published in: Journal of Neuroinflammation | Issue 1/2015

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Park JS, Arcaroli J, Yum HK, Yang H, Wang H, Yang KY. Activation of gene expression in human neutrophils by high mobility group box 1 protein. Am J Physiol. 2003;284:C870–9.CrossRef Park JS, Arcaroli J, Yum HK, Yang H, Wang H, Yang KY. Activation of gene expression in human neutrophils by high mobility group box 1 protein. Am J Physiol. 2003;284:C870–9.CrossRef
2.
go back to reference Stros M, Ozaki T, Bacikova A, Kageyama H, Nakagawara A. HMGB1 and HMGB2 cell-specifically down-regulate the p53- and p73-dependent sequence-specific transactivation from the human Bax gene promoter. J Biol Chem. 2002;277:7157–64.CrossRefPubMed Stros M, Ozaki T, Bacikova A, Kageyama H, Nakagawara A. HMGB1 and HMGB2 cell-specifically down-regulate the p53- and p73-dependent sequence-specific transactivation from the human Bax gene promoter. J Biol Chem. 2002;277:7157–64.CrossRefPubMed
3.
go back to reference Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ. HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol. 2010;28:367–88.CrossRefPubMed Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ. HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol. 2010;28:367–88.CrossRefPubMed
4.
go back to reference Shi Y, Sandoghchian Shotorbani S, Su Z, Liu Y, Tong J, Zheng D, et al. Enhanced HMGB1 expression may contribute to Th17 cells activation in rheumatoid arthritis. Clin Dev Immunol. 2012;2012:295081.CrossRefPubMedCentralPubMed Shi Y, Sandoghchian Shotorbani S, Su Z, Liu Y, Tong J, Zheng D, et al. Enhanced HMGB1 expression may contribute to Th17 cells activation in rheumatoid arthritis. Clin Dev Immunol. 2012;2012:295081.CrossRefPubMedCentralPubMed
5.
go back to reference Abdulahad DA, Westra J, Bijzet J, Limburg PC, Kallenberg CG, Bijl M. High mobility group box 1 (HMGB1) and anti-HMGB1 antibodies and their relation to disease characteristics in systemic lupus erythematosus. Arthritis Res Ther. 2011;13:R71.CrossRefPubMedCentralPubMed Abdulahad DA, Westra J, Bijzet J, Limburg PC, Kallenberg CG, Bijl M. High mobility group box 1 (HMGB1) and anti-HMGB1 antibodies and their relation to disease characteristics in systemic lupus erythematosus. Arthritis Res Ther. 2011;13:R71.CrossRefPubMedCentralPubMed
6.
go back to reference Chen T, Guo ZP, Li L, Wang L, Jia RZ, Cao N, et al. Increased HMGB1 serum levels and altered HMGB1 expression in patients with psoriasis vulgaris. Arch Dermatol Res. 2013;305:263–7.CrossRefPubMed Chen T, Guo ZP, Li L, Wang L, Jia RZ, Cao N, et al. Increased HMGB1 serum levels and altered HMGB1 expression in patients with psoriasis vulgaris. Arch Dermatol Res. 2013;305:263–7.CrossRefPubMed
7.
go back to reference Dupire G, Nicaise C, Gangji V, Soyfoo MS. Increased serum levels of high-mobility group box 1 (HMGB1) in primary Sjögren’s syndrome. Scand J Rheumatol. 2012;41:120–3.CrossRefPubMed Dupire G, Nicaise C, Gangji V, Soyfoo MS. Increased serum levels of high-mobility group box 1 (HMGB1) in primary Sjögren’s syndrome. Scand J Rheumatol. 2012;41:120–3.CrossRefPubMed
8.
go back to reference Andersson A, Covacu R, Sunnemark D, Danilov AI, Dal Bianco A, Khademi M, et al. Pivotal advance: HMGB1 expression in active lesions of human and experimental multiple sclerosis. J Leukoc Biol. 2008;84:1248–55.CrossRefPubMed Andersson A, Covacu R, Sunnemark D, Danilov AI, Dal Bianco A, Khademi M, et al. Pivotal advance: HMGB1 expression in active lesions of human and experimental multiple sclerosis. J Leukoc Biol. 2008;84:1248–55.CrossRefPubMed
9.
go back to reference Robinson AP, Caldis MW, Harp CT, Goings GE, Miller SD. High-mobility group box 1 protein (HMGB1) neutralization ameliorates experimental autoimmune encephalomyelitis. J Autoimmun. 2013;43:32–43.CrossRefPubMedCentralPubMed Robinson AP, Caldis MW, Harp CT, Goings GE, Miller SD. High-mobility group box 1 protein (HMGB1) neutralization ameliorates experimental autoimmune encephalomyelitis. J Autoimmun. 2013;43:32–43.CrossRefPubMedCentralPubMed
10.
go back to reference Uzawa A, Mori M, Taniguchi J, Masuda S, Muto M, Kuwabara S. Anti-high mobility group box 1 monoclonal antibody ameliorates experimental autoimmune encephalomyelitis. Clin Exp Immunol. 2013;172:37–43.CrossRefPubMedCentralPubMed Uzawa A, Mori M, Taniguchi J, Masuda S, Muto M, Kuwabara S. Anti-high mobility group box 1 monoclonal antibody ameliorates experimental autoimmune encephalomyelitis. Clin Exp Immunol. 2013;172:37–43.CrossRefPubMedCentralPubMed
11.
go back to reference Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001;25:402–8.CrossRefPubMed Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001;25:402–8.CrossRefPubMed
12.
go back to reference Gardella S, Andrei C, Ferrera D, Lotti LV, Torrisi MR, Bianchi ME, et al. The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway. EMBO Rep. 2002;3:995–1001.CrossRefPubMedCentralPubMed Gardella S, Andrei C, Ferrera D, Lotti LV, Torrisi MR, Bianchi ME, et al. The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway. EMBO Rep. 2002;3:995–1001.CrossRefPubMedCentralPubMed
13.
go back to reference Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002;418:191–5.CrossRefPubMed Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002;418:191–5.CrossRefPubMed
14.
go back to reference Andersson U, Wang H, Palmblad K, Aveberger AC, Bloom O, Erlandsson-Harris H, et al. High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med. 2000;192:565–70.CrossRefPubMedCentralPubMed Andersson U, Wang H, Palmblad K, Aveberger AC, Bloom O, Erlandsson-Harris H, et al. High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med. 2000;192:565–70.CrossRefPubMedCentralPubMed
15.
go back to reference Sundberg E, Fasth AER, Palmblad K, Harris HE, Andersson U. High mobility group box chromosomal protein 1 acts as a proliferation signal for activated T lymphocytes. Immunobiology. 2009;214:303–9.CrossRefPubMed Sundberg E, Fasth AER, Palmblad K, Harris HE, Andersson U. High mobility group box chromosomal protein 1 acts as a proliferation signal for activated T lymphocytes. Immunobiology. 2009;214:303–9.CrossRefPubMed
16.
go back to reference Schiraldi M, Raucci A, Muñoz LM, Livoti E, Celona B, Venereau E, et al. HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med. 2012;209:551–63.CrossRefPubMedCentralPubMed Schiraldi M, Raucci A, Muñoz LM, Livoti E, Celona B, Venereau E, et al. HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med. 2012;209:551–63.CrossRefPubMedCentralPubMed
Metadata
Title
Role of high mobility group box protein 1 (HMGB1) in peripheral blood from patients with multiple sclerosis
Authors
Sunny Malhotra
Nicolas Fissolo
Mar Tintoré
Ana Cristina Wing
Joaquin Castilló
Angela Vidal-Jordana
Xavier Montalban
Manuel Comabella
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2015
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-015-0269-9

Other articles of this Issue 1/2015

Journal of Neuroinflammation 1/2015 Go to the issue