The inflammatory fingerprint reveals immune cell populations associated with disease activity in cardiac sarcoidosis

Abstract Objective Sarcoidosis is a systemic granulomatous inflammatory disease and patients with cardiac involvement are at increased risk of adverse events. Pathophysiologic processes leading to myocardial inflammation and fibrosis are yet to be determined. Therefore, characterization of the immune response leading to enhanced disease activity and portending poor prognosis of patients with cardiac sarcoidosis (CS) is crucial. Methods Twenty-six patients with biopsy-proven sarcoidosis were prospectively enrolled for evaluation of suspected CS and disease activity was determined by hybrid cardiac PET/MR imaging. We then analyzed the peripheral blood of individuals with active CS (aCS), chronic CS (cCS), extracardiac sarcoidosis (noCS), and healthy controls using a 36-color spectral flow cytometry and immunoassay panel. Results Analysis of the inflammatory fingerprint in patients with CS uncovered 56 characteristic immune cell populations. Immunophenotyping of the inflammatory cells revealed distinctive differences between healthy individuals and patients with sarcoidosis. Further, the abundance of the cell populations was associated with cardiac manifestation and disease activity. A critical shift of lymphocytes, innate immune cells, and monocyte subsets occurred in patients with CS compared to extracardiac sarcoidosis and healthy individuals. In addition, cytokine/chemokine expression was aberrant in patients with CS and may contribute to the cardiac pathophysiology of sarcoidosis. Conclusions Comprehensive characterization of the inflammatory fingerprint reveals changes in frequency and phenotype of several immune cell populations associated with cardiac sarcoidosis. Our results may add further knowledge to the pathophysiology of cardiac sarcoidosis, allowing a better stratification of patients with high disease activity who seem to benefit most from immunosuppressive therapy. Graphical Abstract