Increased serum calpain activity is associated with HMGB1 levels in systemic sclerosis

Wen-Qi Shao,Yue-Mei Yan,Yang Li,Yong Yu,Ji-Na Zheng,Qiang Wang

doi:10.1186/s13075-020-02195-y

Abstract

BackgroundSystemic sclerosis (SSc) or scleroderma is an intractable autoimmune disorder that affects multiple organs. The objectives were to investigate clinical correlations of serum calpain activity and high mobility group box 1 (HMGB1) levels with immunological and clinical traits.MethodsA total of 31 patients with SSc, 20 age- and gender-matched healthy control subjects (HC), and 10 patients with other connective tissue diseases (CTD) were recruited in the study. We measured serum calpain activity and HMGB1 levels and analyzed the datasets (GSE40839, GSE48149, GSE76808, GSE81292, GSE33463, and GSE58095) from Gene Expression Omnibus (GEO) database to explore the potential mechanism by which calpain exerts its function through bioinformatics methods.ResultsSerum calpain activity was significantly increased in patients with SSc compared with those in HC and in patients with CTD and was correlated with serum HMGB1 levels, modified Rodnan skin score, erythrocyte sedimentation rate, mean platelet volume, and plateletcrit. Notably, serum calpain activity and HMGB1 levels in SSc patients with interstitial lung disease (ILD) were significantly higher than those in SSc patients without ILD. Serum calpain activity and HMGB1 levels could be the independent risk factors for SSc-ILD and novel biomarkers in patients with SSc.ConclusionThis is the first study that reports increased serum calpain activity and the correlation between calpain and HMGB1 in patients with SSc or SSc-ILD. The serum calpain activity and HMGB1 levels may serve as measures of ILD in patients with SSc. Also, calpain and HMGB1 could be potential therapeutic targets for patients with SSc or SSc-ILD in the future.

Highlights

Systemic sclerosis (SSc) or scleroderma is an intractable autoimmune disorder that affects multiple organs
Overexpression of calpain-related genes in SSc or SSc-interstitial lung disease (ILD) patients To explore the relationship between calpains and SSc, we compared the expression levels of calpain-related genes between SSc or SSc-ILD patients and healthy control subjects (HC) in five microarray datasets from lung biopsy samples, one from Peripheral blood mononuclear cells (PBMCs) samples and one from skin biopsy samples
We demonstrated that calpain activity in serum of patients with SSc was positively correlated with high mobility group box 1 (HMGB1) levels, modified Rodnan skin score (mRSS), mean platelet volume (MPV), and PCT, but correlated inversely with erythrocyte sedimentation rate (ESR)

Summary

Introduction

Systemic sclerosis (SSc) or scleroderma is an intractable autoimmune disorder that affects multiple organs. Systemic sclerosis (SSc) or scleroderma is an intractable autoimmune disorder characterized by vasculopathy and fibrosis of the skin and visceral organs including the heart, kidney, and lung, which has high mortality and reduced survival than other autoimmune diseases [1]. SSc often involves multiple organs, lung diseases, such as interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), are considered the main causes of mortality [2]. Progress in the development of effective therapies for SSc has been slow [3]. Besides novel biomarkers reflecting the progression of the disease, there is a need to identify the potential targets for accurate therapy in SSc or SSc-ILD.

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