Characterization of cathepsin S as potential biomarkers of Sjögren’s syndrome in mouse models

Unrestricted Sjögren’s syndrome (SjS) is a systemic autoimmune disorder characterized by exocrine dysfunction resulting from immune-mediated attack and associated with defective protein trafficking. Previous studies suggest cathepsins as proteases, function in MHC II-mediated antigen processing in antigen presenting cells (APCs) and thus play a complex role in initiation and progression of autoimmunity. Other work also suggests that these cathepsins may be missorted in animal model of SjS. Since, cathepsins are potentially pathogenic factors in the progression of SjS, we conducted enzymatic assays to quantify and characterize the activities of key cathepsins in NOD mice, - an animal model of SjS- relative to control BALB/c mice. Results suggest that cathepsin S (CATS) and cathepsin H (CATH) activities were significantly higher in lysates of NOD mouse lacrimal gland (LG) than lysates of BALB/c mouse lacrimal gland. CATS activity is significantly elevated in NOD mouse tears. These data suggest that CATS is a potential tear biomarker for diagnosis of dacryoadenitis in SjS.

无限制性干燥综合征（Sjögren’s Syndrome, SjS）是一类以免疫介导的组织损伤引发外分泌功能障碍，并伴随蛋白质运输缺陷为特征的系统性自身免疫性疾病。既往研究表明，组织蛋白酶作为一类蛋白酶，可参与抗原呈递细胞（Antigen Presenting Cells, APCs）中MHC II类分子介导的抗原加工过程，进而在自身免疫应答的起始与进展中发挥复杂调控作用。另有研究显示，在干燥综合征的动物模型中，此类组织蛋白酶可能存在胞内分选异常。鉴于组织蛋白酶可能是干燥综合征进展过程中的潜在致病因子，本研究通过酶学测定实验，对作为干燥综合征动物模型的非肥胖糖尿病（Non-Obese Diabetic, NOD）小鼠与对照BALB/c小鼠体内关键组织蛋白酶的活性进行定量分析与表征。结果显示，NOD小鼠泪腺（Lacrimal Gland, LG）裂解物中组织蛋白酶S（Cathepsin S, CATS）与组织蛋白酶H（Cathepsin H, CATH）的活性显著高于对照BALB/c小鼠的泪腺裂解物；同时，NOD小鼠泪液中的CATS活性显著升高。上述实验数据表明，CATS可作为诊断干燥综合征相关性泪腺炎的潜在泪液生物标志物。