Fahriye Groen-Hakan1, Laura Eurelings2, Josianne C ten Berge1, Jan van Laar2,3, Christian R B Ramakers4, Willem A Dik3,5, Aniki Rothova1. 1. Department of Ophthalmology, Erasmus University Medical Center, Erasmus University, Rotterdam, the Netherlands 2. Department of Internal Medicine, Section of Clinical Immunology, Erasmus University Medical Center, Erasmus University, Rotterdam, the Netherlands 3. Department of Immunology, Erasmus University Medical Center, Erasmus University, Rotterdam, the Netherlands 4. Department of Clinical Chemistry, Erasmus University Medical Center, Erasmus University, Rotterdam, the Netherlands 5. Laboratory Medical Immunology, Erasmus University Medical Center, Erasmus University, Rotterdam, the Netherlands
Abstract
Importance: 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. Objective: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.
Importance: 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. Objective: 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 uveitisoutpatient 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.
Authors: Laura E M Eurelings; Jelle R Miedema; Virgil A S H Dalm; Paul L A van Daele; P Martin van Hagen; Jan A M van Laar; Willem A Dik Journal: PLoS One Date: 2019-10-17 Impact factor: 3.240