Abstract
BackgroundHigh 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.MethodsHMGB1 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).ResultsHMGB1 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).ConclusionsThese 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 materialThe online version of this article (doi:10.1186/s12974-015-0269-9) contains supplementary material, which is available to authorized users.
Highlights
High mobility group box protein 1 (HMGB1) is a transcriptional regulator that is receiving increasing attention in autoimmune disorders including multiple sclerosis (MS)
When we segregated patients on the basis of clinical forms (Figure 1B), HMGB1 expression levels were higher in peripheral blood mononuclear cells (PBMC) from patients with relapse-onset MS, and differences were statistically significant for relapsing-remitting MS (RRMS) patients when compared both with primary progressive MS (PPMS) patients and controls (P = 4 × 10−5 and P = 0.005, respectively), and for SPMS patients when compared with PPMS patients (P = 0.001)
HMGB1 expression levels were similar between the PPMS group and the control group (Figure 1B)
Summary
High mobility group box protein 1 (HMGB1) is a transcriptional regulator that is receiving increasing attention in autoimmune disorders including multiple sclerosis (MS). High mobility group box protein 1 (HMGB1) is a DNAbinding non-histone protein that acts as a transcriptional regulator and nucleosomal stabilizer [1,2]. It is released from activated immune cells, necrotic cells, and apoptotic cells and during secondary necrosis [3]. Based on these observations, in the present study, we aimed to investigate a potential role of HMGB1 in the peripheral blood compartment by determining its expression in Malhotra et al Journal of Neuroinflammation (2015) 12:48 peripheral blood mononuclear cells (PBMC) and circulating levels of HMGB1 in MS patients with different clinical forms and healthy controls
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