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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

Bar graphs comparingHMGB1mRNA expression levels in PBMCs from MS patients and healthy controls (A) and between different clinical forms of MS (B).HMGB1 expression was determined by real-time PCR using GAPDH as endogenous control. Results are expressed as fold change in HMGB1 gene expression in MS patients relative to controls. Errors bars represent standard error of the mean. Number of individuals included in the study is shown in parentheses. 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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Fig1: Bar graphs comparingHMGB1mRNA expression levels in PBMCs from MS patients and healthy controls (A) and between different clinical forms of MS (B).HMGB1 expression was determined by real-time PCR using GAPDH as endogenous control. Results are expressed as fold change in HMGB1 gene expression in MS patients relative to controls. Errors bars represent standard error of the mean. Number of individuals included in the study is shown in parentheses. HC: healthy controls. MS: whole group of multiple sclerosis patients. RR: relapsing-remitting MS. SP: secondary progressive MS. PP: primary progressive MS.

Mentions: We first compared mRNA expression levels for HMGB1 between the whole group of MS patients and healthy controls. As shown in Figure 1A, HMGB1 expression was significantly increased in PBMC from MS patients compared to controls (P = 0.03). When we segregated patients on the basis of clinical forms (Figure 1B), HMGB1 expression levels were higher in PBMC from patients with relapse-onset MS, and differences were statistically significant for RRMS patients when compared both with PPMS patients and controls (P = 4 × 10−5 and P = 0.005, respectively), and also for SPMS patients when compared with PPMS patients (P = 0.001). A trend towards increased mRNA expression levels of HMGB1 was observed in SPMS patients when compared with controls (P = 0.05). HMGB1 expression levels were similar between the PPMS group and the control group (Figure 1B).Figure 1


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)

Bar graphs comparingHMGB1mRNA expression levels in PBMCs from MS patients and healthy controls (A) and between different clinical forms of MS (B).HMGB1 expression was determined by real-time PCR using GAPDH as endogenous control. Results are expressed as fold change in HMGB1 gene expression in MS patients relative to controls. Errors bars represent standard error of the mean. Number of individuals included in the study is shown in parentheses. 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

Fig1: Bar graphs comparingHMGB1mRNA expression levels in PBMCs from MS patients and healthy controls (A) and between different clinical forms of MS (B).HMGB1 expression was determined by real-time PCR using GAPDH as endogenous control. Results are expressed as fold change in HMGB1 gene expression in MS patients relative to controls. Errors bars represent standard error of the mean. Number of individuals included in the study is shown in parentheses. HC: healthy controls. MS: whole group of multiple sclerosis patients. RR: relapsing-remitting MS. SP: secondary progressive MS. PP: primary progressive MS.
Mentions: We first compared mRNA expression levels for HMGB1 between the whole group of MS patients and healthy controls. As shown in Figure 1A, HMGB1 expression was significantly increased in PBMC from MS patients compared to controls (P = 0.03). When we segregated patients on the basis of clinical forms (Figure 1B), HMGB1 expression levels were higher in PBMC from patients with relapse-onset MS, and differences were statistically significant for RRMS patients when compared both with PPMS patients and controls (P = 4 × 10−5 and P = 0.005, respectively), and also for SPMS patients when compared with PPMS patients (P = 0.001). A trend towards increased mRNA expression levels of HMGB1 was observed in SPMS patients when compared with controls (P = 0.05). HMGB1 expression levels were similar between the PPMS group and the control group (Figure 1B).Figure 1

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