Ace levels in sarcoidosis
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Serum ACE Levels as a Biomarker in Sarcoidosis Diagnosis
Serum angiotensin-converting enzyme (ACE) levels are often elevated in patients with active sarcoidosis, making ACE a commonly used biomarker in clinical practice for this disease. Studies consistently show that patients with sarcoidosis have higher median ACE values compared to those without the disease, and that ACE levels tend to decrease with disease resolution or corticosteroid therapy 123. However, the sensitivity and specificity of ACE for diagnosing sarcoidosis are limited, and many patients with sarcoidosis may have ACE levels within the normal range 1459.
Diagnostic Sensitivity, Specificity, and Cut-off Values for ACE in Sarcoidosis
The sensitivity of elevated ACE for detecting sarcoidosis varies widely, reported between 21% and 80% depending on the cut-off value and population studied 1459. For example, using a lower cut-off value (such as 14.7 IU/L or 17.7 IU/L) increases sensitivity but reduces specificity and positive predictive value, while higher cut-offs improve specificity but miss more cases 19. The positive predictive value of an elevated ACE is generally low, but the negative predictive value is high, meaning a normal ACE level makes sarcoidosis less likely but does not rule it out 45.
ACE Levels and Disease Activity
Elevated ACE levels are most strongly associated with active sarcoidosis and tend to normalize with effective treatment or disease remission 23. However, the correlation between ACE levels and disease activity is not always consistent, and some studies have found no significant difference in ACE levels between active and remission phases in paired analyses . Serial monitoring of ACE can be useful for tracking response to therapy in some patients, but its utility is limited by variability and lack of specificity 236.
Factors Affecting ACE Levels: Medications and Genetic Polymorphisms
ACE inhibitor medications significantly lower serum ACE levels, which can confound interpretation in patients being evaluated for sarcoidosis 16. Additionally, genetic polymorphisms in the ACE gene (insertion/deletion variants) influence baseline ACE levels, with the DD genotype associated with the highest ACE levels and the II genotype with the lowest 810. Adjusting normal ranges for ACE based on genotype can improve diagnostic sensitivity .
Specificity and Limitations of ACE as a Sarcoidosis Marker
While elevated ACE is a useful supportive marker for sarcoidosis, it is not specific to the disease. Other conditions, such as Gaucher’s disease, non-Hodgkin’s lymphoma, cirrhosis, and interstitial lung disease, can also cause elevated ACE 245. Most other chronic lung diseases, however, are associated with normal or even reduced ACE levels . Newer approaches, such as ACE phenotyping and immunoreactivity assays, may improve the sensitivity and specificity for detecting systemic or extrapulmonary sarcoidosis, but these are not yet widely used .
Conclusion
Serum ACE is a helpful but imperfect biomarker for sarcoidosis. Elevated ACE supports the diagnosis, especially in active disease, but normal levels do not exclude sarcoidosis. The test’s sensitivity and specificity are limited, and results must be interpreted in the context of clinical findings, medication use, and genetic background. Careful consideration of these factors is essential for optimal use of ACE in the diagnosis and management of sarcoidosis 14568910.
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