Department of Dermatology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, People's Republic of China.
Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Arthritis Res Ther. 2020 May 11;22(1):110. doi: 10.1186/s13075-020-02195-y.
Systemic 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.
A 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.
Serum 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.
This 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.
系统性硬化症（SSc）或硬皮病是一种影响多个器官的难治性自身免疫性疾病。本研究旨在探讨血清钙蛋白酶活性和高迁移率族蛋白 1（HMGB1）水平与免疫和临床特征的临床相关性。
本研究共纳入 31 例 SSc 患者、20 名年龄和性别匹配的健康对照者（HC）和 10 名其他结缔组织疾病（CTD）患者。我们测量了血清钙蛋白酶活性和 HMGB1 水平，并通过生物信息学方法分析了来自基因表达综合数据库（GEO）的数据集（GSE40839、GSE48149、GSE76808、GSE81292、GSE33463 和 GSE58095），以探讨钙蛋白酶发挥作用的潜在机制。
与 HC 和 CTD 患者相比，SSc 患者的血清钙蛋白酶活性显著升高，且与血清 HMGB1 水平、改良 Rodnan 皮肤评分、红细胞沉降率、平均血小板体积和血小板分布宽度相关。值得注意的是，有间质性肺病（ILD）的 SSc 患者的血清钙蛋白酶活性和 HMGB1 水平明显高于无 ILD 的 SSc 患者。血清钙蛋白酶活性和 HMGB1 水平可能是 SSc-ILD 的独立危险因素，也是 SSc 患者的新型生物标志物。
这是第一项报道 SSc 或 SSc-ILD 患者血清钙蛋白酶活性增加及其与钙蛋白酶和 HMGB1 相关性的研究。血清钙蛋白酶活性和 HMGB1 水平可作为 SSc 患者ILD 的指标。此外，钙蛋白酶和 HMGB1 可能成为未来 SSc 或 SSc-ILD 患者的潜在治疗靶点。
