Association of serum/plasma high mobility group box 1 with autoimmune diseases: A systematic review and meta-analysis

BACKGROUND: High mobility group box 1 (HMGB1) is a kind of proinflammatory mediator to stimulate the innate and adaptive immune system and participates in a number of acute and chronic inflammatory processes after sterile injury or microbial invasion. HMGB1 has been suggested to be involved in the pathogenesis of many autoimmune diseases. However, the results are contradictory or inconclusive among these findings. The aim of this study was to investigate whether serum/plasma HMGB1 levels are associated with autoimmune diseases by comparing the serum/plasma HMGB1 levels in patients with autoimmune disease and healthy controls and to further evaluate whether serum/plasma HMGB1 levels are associated with disease state. METHODS: PubMed, Medline, and Web of science databases (up to October 1, 2017) were used to obtain all relative published literature. Study quality was assessed by the Newcastle–Ottawa scale (NOS). Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. RESULTS: A total of 23 original articles of autoimmune diseases were finally included in the meta-analysis. Results revealed that the serum/plasma HMGB1 levels were increased in patients with autoimmune disease, compared to healthy controls. Subgroup analysis showed that serum/plasma HMGB1 levels in patients with active disease state were significantly higher than in those with inactive state. In addition, subgroup analysis based on disease type has indicated that the serum/plasma HMGB1 levels in patients with small vessel vasculitis, systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis and sjogren syndrome were significantly higher, compared to healthy controls. Further subgroup analyses by region showed that plasma/serum HMGB1 levels were higher in Asian and European patients with autoimmune diseases. CONCLUSIONS: Serum/plasma HMGB1 levels in patients with autoimmune diseases are significantly higher than in healthy controls, and may reflect the disease activity.