Department of Ophthalmology, Erasmus University Medical Center, Erasmus University, Rotterdam, the Netherlands
Department of Internal Medicine, Section of Clinical Immunology, Erasmus University Medical Center, Erasmus University, Rotterdam, the Netherlands
JAMA Ophthalmol. 2017 Dec 1;135(12):1352-1358. doi: 10.1001/jamaophthalmol.2017.4771.
New and improved diagnostic tests for sarcoidosis-associated uveitis are needed because the currently available laboratory diagnostic biomarkers (eg, lysozyme and angiotensin-converting enzyme [ACE]) are lacking in high sensitivity and specificity.
To compare the value of soluble interleukin 2 receptor (sIL-2R) with ACE as diagnostic biomarkers of sarcoidosis in patients with uveitis.
DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional retrospective study was conducted using data collected from 249 consecutive patients with uveitis at the Erasmus University Medical Center uveitis outpatient clinic, Rotterdam, the Netherlands, from April 3, 2013, through November 25, 2015. Measurements of sIL-2R and ACE in serum samples and data extraction from patient files were conducted from December 2016 through February 2017, and analysis from April to May 2017.
Serum levels of sIL-2R and ACE and chest radiographic findings were assessed. Receiver operating characteristics analysis was used to determine the probability that individual tests correctly identified patients with sarcoidosis. The Youden Index was used to determine the optimal cutoff points for serum sIL-2R and ACE levels to define sarcoidosis in patients with uveitis.
Data were analyzed from 249 patients with uveitis who had their serum sIL-2R and ACE levels determined and underwent chest radiography. Mean (SD) age at the time of sampling was 51 (16) years, 161 patients (64.7%) were women, and 191 (76.7%) were white. Although patients with sarcoidosis-associated uveitis had the highest mean (SD) serum sIL-2R (6047 [2533] pg/mL) and ACE (61 [38] U/L) levels, elevated serum sIL-2R levels were also found in patients with HLA-B27–associated (4460 [2465] pg/mL) and varicella-zoster virus–associated (5386 [1778] pg/mL) uveitis. Serum sIL-2R and ACE levels were significantly correlated (Pearson correlation coefficient, 0.205; P = .001, 2-sided), but no association was found between uveitis activity and sIL-2R (Spearman rank correlation coefficient [ρ], 0.070, P = .27) nor uveitis activity and ACE (ρ, −0.071; P = .27). The highest Youden index for sIL-2R alone was 0.45, corresponding to an optimal cutoff of 4000 pg/mL and providing 81% (95% CI, 74%-89%) sensitivity and 64% (95% CI, 56%-72%) specificity alone but combined with chest radiography yielded 92% sensitivity and 58% specificity. Chest radiography combined with sIL-2R at a cutoff of 6000 pg/mL resulted in 77% sensitivity and 73% specificity. Combined chest radiography and serum ACE levels at the standard cutoff of 68 U/L resulted in 70% sensitivity and 79% specificity.
This cross-sectional study demonstrates that sIL-2R is a useful marker for diagnosing sarcoidosis in patients with uveitis and has slightly better diagnostic value than ACE.
需要新的和改进的用于诊断结节病相关性葡萄膜炎的检测方法,因为目前可用的实验室诊断生物标志物(例如,溶菌酶和血管紧张素转换酶[ACE])在灵敏度和特异性方面都存在不足。
比较可溶性白细胞介素 2 受体(sIL-2R)与 ACE 作为葡萄膜炎患者结节病的诊断生物标志物的价值。
设计、设置和参与者:这是一项横断面回顾性研究,在荷兰鹿特丹伊拉斯谟大学医学中心葡萄膜炎门诊共纳入了 249 例连续就诊的葡萄膜炎患者,纳入时间为 2013 年 4 月 3 日至 2015 年 11 月 25 日,对其血清样本中 sIL-2R 和 ACE 进行测量,并从患者病历中提取数据。血清 sIL-2R 和 ACE 水平的测量和分析于 2016 年 12 月至 2017 年 2 月进行,分析于 2017 年 4 月至 5 月进行。
评估血清 sIL-2R 和 ACE 水平以及胸部 X 线表现。采用受试者工作特征曲线分析确定单项检查正确识别出患有结节病的患者的概率。采用约登指数确定血清 sIL-2R 和 ACE 水平的最佳截断点,以定义患有葡萄膜炎的患者患有结节病。
共分析了 249 例接受血清 sIL-2R 和 ACE 水平检测并接受胸部 X 线检查的葡萄膜炎患者的数据。检测时的平均(SD)年龄为 51(16)岁,161 例(64.7%)为女性,191 例(76.7%)为白人。尽管结节病相关性葡萄膜炎患者的血清 sIL-2R(6047 [2533] pg/mL)和 ACE(61 [38] U/L)水平最高,但 HLA-B27 相关性(4460 [2465] pg/mL)和水痘带状疱疹病毒相关性(5386 [1778] pg/mL)葡萄膜炎患者的血清 sIL-2R 水平也升高。血清 sIL-2R 和 ACE 水平呈显著相关(Pearson 相关系数,0.205;P = .001,双侧),但葡萄膜炎活动度与 sIL-2R 之间(Spearman 秩相关系数[ρ],0.070;P = .27)和与 ACE 之间(ρ,−0.071;P = .27)均无关联。sIL-2R 单独的最佳约登指数为 0.45,对应的最佳截断值为 4000 pg/mL,其单独检测的灵敏度为 81%(95%CI,74%-89%),特异性为 64%(95%CI,56%-72%),但与胸部 X 线检查联合检测的灵敏度为 92%,特异性为 58%。胸部 X 线检查与 sIL-2R 截断值为 6000 pg/mL 联合检测,灵敏度为 77%,特异性为 73%。胸部 X 线检查和 ACE 水平标准截断值 68 U/L 联合检测,灵敏度为 70%,特异性为 79%。
这项横断面研究表明,sIL-2R 是诊断葡萄膜炎患者结节病的有用标志物,其诊断价值略优于 ACE。