Immunological biomarkers predict pulmonary and nodal, but not cardiac positron emission tomography-assessed sarcoidosis activity.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease with highly variable clinical manifestations and organ involvement. Symptoms are often unspecific or absent and may not reflect true inflammatory burden, increasing the risk of delayed detection of organ damage. Reliable assessment of disease activity is therefore essential for treatment guidance. We aimed to investigate the correlation and predictive performance of circulating biomarkers with systemic inflammatory activity as assessed by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT), exploring whether a biomarker-based approach could substitute more resource-intensive imaging. METHODS: We conducted a retrospective cohort study including 180 patients with systemic sarcoidosis who underwent paired 18F-FDG PET-CT and blood sampling (n=770). Systemic biomarkers including tumour necrosis factor-α (TNF-α), soluble interleukin-2 receptor (sIL-2R), neopterin, angiotensin-converting enzyme (ACE) activity, C-reactive protein (CRP), calciuria and lymphocytopenia were assessed for their association with PET-based inflammatory activity. Variance and correlation analyses as well as receiver operating characteristic curves were used to evaluate diagnostic performance. RESULTS: TNF-α, sIL-2R and neopterin consistently showed significant correlation with PET activity already for moderate inflammatory activity (activity-quartile 2-3 versus inactive: p<0.001), with TNF-α showing the best predictive ability, though overall degree of correlation remained moderate (Pearson's r<0.5; area under the curve: 0.63-0.68). Traditional biomarkers such as ACE activity and CRP only showed significant differences at the highest quartile of PET activity (activity-quartile 4 versus inactive p<0.001 and p=0.005, respectively). While biomarker correlations were evident for pulmonary and nodal inflammation, weak to no association was found for PET-assessed cardiac activity. CONCLUSION: Immunological biomarkers such as TNF-α, sIL-2R and neopterin outperform traditional markers such as CRP and ACE activity, and should be considered in the assessment of systemic sarcoidosis activity at diagnosis and follow-up. Since no biomarker was able to predict cardiac inflammatory activity, imaging techniques such as magnetic resonance imaging and 18F-FDG PET remain central for diagnosis and exclusion of cardiac sarcoidosis.