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Optimized angiotensin-converting enzyme activity assay for the accurate diagnosis of sarcoidosis

A. Csongrádi,A. Enyedi,I. Takács,T. Végh,I. S. Mányiné,Z. Pólik,I. Altorjay,J. Balla,G. Balla,I. Edes,J. Kappelmayer,A. Tóth,Z. Papp,M. Fagyas

Published 2018 in Clinical Chemistry and Laboratory Medicine

ABSTRACT

Abstract Background: Serum angiotensin-converting enzyme (ACE) activity determination can aid the early diagnosis of sarcoidosis. We aimed to optimize a fluorescent kinetic assay for ACE activity by screening the confounding effects of endogenous ACE inhibitors and interfering factors. Genotype-dependent and genotype-independent reference values of ACE activity were established, and their diagnostic accuracies were validated in a clinical study. Methods: Internally quenched fluorescent substrate, Abz-FRK(Dnp)P-OH was used for ACE-activity measurements. A total of 201 healthy individuals and 59 presumably sarcoidotic patients were enrolled into this study. ACE activity and insertion/deletion (I/D) genotype of the ACE gene were determined. Results: Here we report that serum samples should be diluted at least 35-fold to eliminate the endogenous inhibitor effect of albumin. No significant interferences were detected: up to a triglyceride concentration of 16 mM, a hemoglobin concentration of 0.71 g/L and a bilirubin concentration of 150 μM. Genotype-dependent reference intervals were considered as 3.76–11.25 U/L, 5.22–11.59 U/L, 7.19–14.84 U/L for II, ID and DD genotypes, respectively. I/D genotype-independent reference interval was established as 4.85–13.79 U/L. An ACE activity value was considered positive for sarcoidosis when it exceeded the upper limit of the reference interval. The optimized assay with genotype-dependent reference ranges resulted in 42.5% sensitivity, 100% specificity, 100% positive predictive value and 32.4% negative predictive value in the clinical study, whereas the genotype-independent reference range proved to have inferior diagnostic efficiency. Conclusions: An optimized fluorescent kinetic assay of serum ACE activity combined with ACE I/D genotype determination is an alternative to invasive biopsy for confirming the diagnosis of sarcoidosis in a significant percentage of patients.

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