University of Southern California School of Pharmacy, Los Angeles.
Arthritis Rheumatol. 2014 Jul;66(7):1872-81. doi: 10.1002/art.38633.
The diagnosis of Sjögren's syndrome (SS) in routine practice is largely a clinical one and requires a high index of suspicion by the treating physician. This great dependence on clinical judgment frequently leads to delayed diagnosis or misdiagnosis. Tear protein profiles have been proposed as simple and reliable biomarkers for the diagnosis of SS. Given that cathepsin S activity is increased in the lacrimal glands and tears of NOD mice (a murine model of SS), the aim of this study was to explore the clinical utility of using tear cathepsin S (CTSS) activity as a biomarker for SS.
A method to measure CTSS activity in tears eluted from Schirmer's test strips was developed and validated. Schirmer's tests were performed and CTSS activity measurements were obtained in 278 female subjects, including 73 with SS, 79 with rheumatoid arthritis, 40 with systemic lupus erythematosus, 10 with blepharitis, 31 with nonspecific dry eye disease, and 12 with other autoimmune diseases, as well as 33 healthy control subjects.
The median tear CTSS activity in patients with SS was 4.1-fold higher than that in patients with other autoimmune diseases, 2.1-fold higher than that in patients with nonspecific dry eye disease, and 41.1-fold higher than that in healthy control subjects. Tear CTSS levels were equally elevated in patients with primary SS and those with secondary SS, independent of the Schirmer's test strip values or the levels of circulating anti-SSA or anti-SSB antibodies.
Markedly high levels of tear CTSS activity are suggestive of SS. CTSS activity in tears can be measured in a simple, quick, economical, and noninvasive manner and may serve as a novel biomarker for autoimmune dacryoadenitis during the diagnostic evaluation for SS.
在常规实践中，干燥综合征（SS）的诊断主要是临床诊断，需要治疗医生有很高的怀疑指数。这种对临床判断的高度依赖常常导致诊断延迟或误诊。泪蛋白谱已被提议作为 SS 诊断的简单可靠的生物标志物。鉴于组织蛋白酶 S 活性在 NOD 小鼠（SS 的一种鼠模型）的泪腺和泪液中增加，本研究旨在探索使用泪液组织蛋白酶 S（CTSS）活性作为 SS 生物标志物的临床实用性。
开发并验证了从 Schirmer 测试条洗脱的泪液中 CTSS 活性的测量方法。对 278 名女性受试者进行了 Schirmer 测试，并获得了 CTSS 活性测量值，其中 73 名患有 SS，79 名患有类风湿关节炎，40 名患有系统性红斑狼疮，10 名患有睑缘炎，31 名患有非特异性干眼症，12 名患有其他自身免疫性疾病，以及 33 名健康对照。
SS 患者的中位泪 CTSS 活性比其他自身免疫性疾病患者高 4.1 倍，比非特异性干眼症患者高 2.1 倍，比健康对照组高 41.1 倍。原发性 SS 和继发性 SS 患者的泪 CTSS 水平均升高，与 Schirmer 测试条值或循环抗 SSA 或抗 SSB 抗体水平无关。
显著升高的泪 CTSS 活性提示 SS。泪液 CTSS 活性可以以简单、快速、经济和非侵入性的方式进行测量，并且可以作为 SS 诊断评估中自身免疫性泪腺炎的新型生物标志物。
