Specific Pro-Inflammatory Signaling Pathways are Induced in Patients with Cardiac Sarcoidosis; Potential Prognostic/Therapeutic Applications

Introduction While cardiac imaging has improved the diagnosis and risk assessment for cardiac sarcoidosis, treatment regimens have consisted of generalized heart failure (HF) therapies and non-specific anti-inflammatory regimens. Thus, improvements in identifying the relative progression of this cardiovascular condition as well as identifying more specific therapeutic targets are necessary. The overall goal of this study was to perform high sensitivity plasma profiling of specific inflammatory pathways in patients with suspected cardiac sarcoidosis. Hypothesis Using large format arrays, specific inflammatory signaling cascades will be upregulated in cardiac sarcoid patients when compared to age matched referent normal subjects. Methods Plasma samples were collected from patients with biopsy confirmed sarcoidosis undergoing F-18 fluorodeoxyglucose (FDG) positron emission tomography (FDG-PET) (n=32; age 32-75 yrs) and compared to referent normal subjects. Using a high sensitivity, automated multiplex array, soluble cytokine receptor profiles (an index of cytokine activation) were measured and then indexed to referent normal values (Table). As a composite, soluble receptor levels for interleukin (IL)-1, -2, and epidermal growth factor (EGFR) were increased in sarcoid patients. In those patients with cardiac inflammation (FDG uptake), IL-1RII and IL-2Ra subtype receptor levels were higher when compared to no cardiac inflammation as was the soluble tumor necrosis factor receptor-II. Conclusions The novel finding from this study was the identification of increased activation of a cluster of soluble receptors, which not only augment inflammatory cell maturation but also transmigration in patients with sarcoidosis and cardiac involvement. The specific change in a cluster of IL receptors may hold prognostic value in cardiac sarcoidosis as well as the potential for more specific therapeutic targeting.