Background/Purpose: Sarcoidosis is a heterogenous granulomatous inflammatory disease that is especially dangerous when it affects the heart where it may cause fatal arrythmias and heart failure. Prompt initiation of therapy is frequently necessary, but treatment goals or targets are unclear, and there is currently no standardized approach for measuring disease activity. Imaging modalities such as PET or cardiac MRI have been used but are expensive and not always accessible. Laboratory tests such as serum calcium or serum ACE level are nonspecific. Activated macrophages are important in the pathogenesis of sarcoidosis granuloma formation and macrophages secrete adenosine deaminase 2 (ADA2) in plasma. ADA2 has been shown to correlate with disease activity in other macrophage-activated diseases such as macrophage activation syndrome and tuberculosis; however, ADA2 activity levels in systemic and cardiac sarcoidosis are not known. Total ADA levels have been shown to correlate with systemic sarcoidosis disease activity. We hope to investigate whether ADA2 may fill the gap that is needed for better diagnostics to assess disease activity and/or treatment responsiveness in cardiac and/or systemic sarcoidosis.

Methods: Patients with cardiac sarcoidosis and a control group of systemic sarcoidosis were examined.Plasma ADA2 levels for normal controls have been previously established since the ADA2 test at Duke University is CLIA certified. ADA2 activity was assessed by spectrophotometric assay and high-performance liquid chromatography. Disease activity at the time of ADA2 lab draw was retrieved by chart review for patients at our institution.

Results: Thirty-five patients with sarcoidosis have currently been studied – eleven from outside of our institution and twenty-four from within. All patients with systemic sarcoidosis had a higher mean ADA2 level (19 ± 13mU/mL) than all patients with isolated cardiac sarcoidosis (13 ± 4 mU/mL). Duke patients with untreated systemic sarcoidosis (23 ± 14 mU/mL) and those with untreated isolated cardiac sarcoidosis (16 ± 10 mU/mL) had mean ADA levels higher than controls. TNF inhibition lowered ADA2 levels in all Duke patients (mean of 16 mU/mL untreated vs. 10 mU/mL treated). All results did not reach statistical significance due to small sample size.

Conclusion: This pilot study suggests that the Duke CLIA-certified plasma ADA2 measurement could serve as a cost-effective, accessible, plasma-based biomarker for cardiac and systemic sarcoidosis that correlates with disease activity and treatment responsiveness. Our data is limited by sample size but suggest that future study in larger numbers of patients is warranted.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pilot-study-investigating-adenosine-deaminase-2-as-a-disease-activity-biomarker-for-cardiac-sarcoidosis/