The Comparative Value of Serum Angiotensin Converting Enzyme (ACE) and Lysozyme and the Use of Polyclonal Antibody Activation in the Work-up of Ocular Sarcoidosis

Background: The diagnosis of ocular sarcoidosis (OS) is difficult to establish in the absence of manifest systemic involvement. To help clinicians reach a diagnosis, we convened a group of experts in 2006 (International Workshop on Ocular Sarcoidosis (IWOS)) to set-up clinical criteria for the diagnosis of ocular sarcoidosis. In addition, laboratory investigational tests represent a much-needed adjunct to ascertain the diagnosis. However, many of these tests have low sensitivity and specificity.

Purpose: The aim of our study was to evaluate the usefulness of serum ACE, serum lysozyme and polyclonal antibody activation in the diagnosis of ocular sarcoidosis and compare the frequency of increased serum levels of lysozyme and ACE in proven ocular sarcoidosis or in suspected ocular sarcoidosis.

Methods: Serum ACE and lysozyme were assessed in these two groups and their means compared to a group of non-granulomatous (i.e., non-sarcoidosis) uveitis patients. The proportion of elevated serum ACE versus lysozyme was compared in the sarcoidosis patients. Polyclonal antibody activation was measured by establishing exposition of patients to four human commensal herpesviruses (EBV, CMV, HSV and VZV) using ELISA or immunofluorescence and in parallel by performing quantitative complement fixation (CF) serologies. The ratio of elevated CF to positive ELISA/immunofluorescence serologies was calculated. The mean of ratios (polyclonal antibody activation) was compared between ocular sarcoidosis and control groups.

Results: Thirty-seven patients (F24/M13) were included in our study including 17 patients with IWOS Level 1 and 2 criteria qualifying for Group 1 (proven sarcoidosis) and 20 ocular sarcoidosis suspect patients. Mean age was 54.52 ± 23.74. Mean serum levels of ACE was 49.17± 29 IU/L in the ocular sarcoidosis group versus 27.4 ± 15.34 IU/L (p ≤ 0.00018, student's t test) in the control group. Mean serum lysozyme levels was 39.92 ± 55.5 mg/L in the ocular sarcoidosis group versus 10.5 ± 5.8 mg/L (p ≤ 0.0013) in the control group (n = 30). Both tests were elevated in 8/37 (21.6%) patients, elevated ACE and normal lysozyme was noted in 2/37 (5.4%) patients, whereas the proportion of normal ACE/elevated lysozyme was much higher, 23/37 (62.2%). In 4/37 (10.8%) patients, both tests were normal. The mean score of polyclonal activation (N of elevated CF serologies divided by number of viruses to which a patient was exposed) was 0.6 ± 0.33 in the ocular sarcoidosis group versus 0.15 ± 0.2 for the control group (n = 42) (p ≤ 0.00001). Sensitivity and specificity of ACE and lysozyme were, respectively, 27%/96.6% and 83.7%/90%. Sensitivity and specificity of polyclonal antibody activation amounted to 70%/90.4% Conclusion: Lysozyme was found to be much more useful than ACE as a laboratory test to support the diagnosis of ocular sarcoidosis. As shown in a previous study, polyclonal antibody activation appears to be another useful laboratory test supportive of the diagnosis of ocular sarcoidosis.