Relationship of High-mobility group box 1 levels and multiple sclerosis: A systematic review and meta-analysis

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system (CNS) affecting more than 2.5 million people worldwide. However, the exact etiology of MS remains unknown, recent research indicated that High-mobility group box 1(HMGB1) might contribute to MS pathogenesis. By evaluating HMGB1 levels of peripheral blood mononuclear cells (PBMC), serum and cerebrospinal fluid (CSF) in multiple sclerosis (MS) patients and the controls, to reveal the relationship of HMGB1 levels and MS patients.

The PubMed, EMBASE, the Cochrane library, China National Knowledge Infrastructure (CNKI) and WanFangData were searched for relevant studies. Pooled standardized mean difference (SMD) and 95% confidence interval (CI) were calculated as effect size, random-effects model was used when I² > 50%. Subgroup analysis was conducted by subtype of MS, categories of controls, country and mean age.

A total of 7 studies with 364 patients of MS and 222 controls were included. The results of this study showed that HMGB1 protein levels of PBMC and CSF in patients with MS were significantly higher than those of controls (SMD = 4.36, 95% CI = 3.69-5.02, and SMD = 0.85, 95% CI = 0.42-1.28, respectively), but we found no significant difference in HMGB1 mRNA level of PBMC and serum HMGB1 protein level between MS patients and controls. In the subgroup analysis, RRMS patients had a higher HMGB1 level in serum (p < 0.05) and CSF (p < 0.01) compared to healthy controls and non-inflammatory neurological disorder controls. In Asians, MS patients had a considerably higher HMGB1 level in serum (p < 0.05), PBMC (protein) (p < 0.01) and CSF (p < 0.01) compared to healthy controls and non-inflammatory neurological disorder controls.

MS patients had higher HMGB1 protein levels in PBMC and CSF compared to controls. HMGB1 might be a new treatment target for MS.