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

Malhotra S, Fissolo N, Tintoré M, Wing AC, Castilló J, Vidal-Jordana A, Montalban X, Comabella M - J Neuroinflammation (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Receca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. sunnymalhotra4u24@gmail.com.

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.

No MeSH data available.


Related in: MedlinePlus

Box plots showing serum levels of HMGB1 in the whole MS group and controls (A) and in MS patients with different clinical forms of MS (B). Serum levels of HMGB1 were measured using a commercially available ELISA, as described in ‘Methods.’ For the sake of clarity, only significant P values are shown in the graphs. Number of individuals included in the study is shown in parentheses. Eleven patients with RRMS, five with SPMS, and eight with PPMS were also included in the HMGB1 gene expression study. HC: healthy controls. MS: whole group of multiple sclerosis patients. RR: relapsing-remitting MS. SP: secondary progressive MS. PP: primary progressive MS.
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Fig2: Box plots showing serum levels of HMGB1 in the whole MS group and controls (A) and in MS patients with different clinical forms of MS (B). Serum levels of HMGB1 were measured using a commercially available ELISA, as described in ‘Methods.’ For the sake of clarity, only significant P values are shown in the graphs. Number of individuals included in the study is shown in parentheses. Eleven patients with RRMS, five with SPMS, and eight with PPMS were also included in the HMGB1 gene expression study. HC: healthy controls. MS: whole group of multiple sclerosis patients. RR: relapsing-remitting MS. SP: secondary progressive MS. PP: primary progressive MS.

Mentions: As shown in Figure 2A, HMGB1 protein levels paralleled HMGB1 mRNA expression levels, and serum levels were significantly increased in the whole MS group compared to the healthy control group (P = 2 × 10−4). When MS patients were stratified according to the different clinical forms, the highest HMGB1 serum levels were observed in patients with RRMS, and differences were statistically significant compared to PPMS patients (P = 5 × 10−5), SPMS patients (P = 0.001), and healthy controls (P = 0.001) (Figure 2B). In the SPMS group, statistically significant differences were only observed with the healthy control group (P = 0.007) but not with the PPMS group (P = 0.1). A trend towards increased serum levels of HMGB1 was observed in PPMS patients compared with controls (P = 0.01).Figure 2


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

Malhotra S, Fissolo N, Tintoré M, Wing AC, Castilló J, Vidal-Jordana A, Montalban X, Comabella M - J Neuroinflammation (2015)

Box plots showing serum levels of HMGB1 in the whole MS group and controls (A) and in MS patients with different clinical forms of MS (B). Serum levels of HMGB1 were measured using a commercially available ELISA, as described in ‘Methods.’ For the sake of clarity, only significant P values are shown in the graphs. Number of individuals included in the study is shown in parentheses. Eleven patients with RRMS, five with SPMS, and eight with PPMS were also included in the HMGB1 gene expression study. HC: healthy controls. MS: whole group of multiple sclerosis patients. RR: relapsing-remitting MS. SP: secondary progressive MS. PP: primary progressive MS.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4359557&req=5

Fig2: Box plots showing serum levels of HMGB1 in the whole MS group and controls (A) and in MS patients with different clinical forms of MS (B). Serum levels of HMGB1 were measured using a commercially available ELISA, as described in ‘Methods.’ For the sake of clarity, only significant P values are shown in the graphs. Number of individuals included in the study is shown in parentheses. Eleven patients with RRMS, five with SPMS, and eight with PPMS were also included in the HMGB1 gene expression study. HC: healthy controls. MS: whole group of multiple sclerosis patients. RR: relapsing-remitting MS. SP: secondary progressive MS. PP: primary progressive MS.
Mentions: As shown in Figure 2A, HMGB1 protein levels paralleled HMGB1 mRNA expression levels, and serum levels were significantly increased in the whole MS group compared to the healthy control group (P = 2 × 10−4). When MS patients were stratified according to the different clinical forms, the highest HMGB1 serum levels were observed in patients with RRMS, and differences were statistically significant compared to PPMS patients (P = 5 × 10−5), SPMS patients (P = 0.001), and healthy controls (P = 0.001) (Figure 2B). In the SPMS group, statistically significant differences were only observed with the healthy control group (P = 0.007) but not with the PPMS group (P = 0.1). A trend towards increased serum levels of HMGB1 was observed in PPMS patients compared with controls (P = 0.01).Figure 2

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Receca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. sunnymalhotra4u24@gmail.com.

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.

No MeSH data available.


Related in: MedlinePlus