Anna Carolina Smed Sörensen

BACKGROUND Sarcoidosis is an inflammatory granulomatous multiorgan disease where 90% have pathology in their lungs and lung draining lymph nodes. It is an enigmatic and challenging disease: the cause is unknown, the clinical outcome spans from spontaneous resolution to organ failure, and there are no sarcoidosis specific treatments available. The breath of clinical disease progression is thought to be dictated by how the immune system reacts but precisely what immunological events dictate disease trajectory remains unknown. AIMS We conduct immunological studies to understand sarcoidosis pathogenesis with the goal to improve early diagnosis and predict disease outcome using novel biomarkers and targetable immune pathways. Specifically, we will study 1. The kinetics and cellular source of the proinflammatory cytokine TNF in patients with or without anti-TNF treatment to evaluate if monitoring TNF from time of diagnosis is useful as a prognostic marker and/or a marker to initiate (early) anti-TNF therapy. 2. The cellular composition and function of pulmonary sarcoid granulomas to decipher fundamental sarcoidosis immunopathology. 3. The role of autoantibodies in sarcoidosis pathogenesis and their potential as diagnostic disease markers. WORKPLAN We utilize clinically well characterized longitudinal sarcoidosis samples across disease severity from blood and tissues to conduct high-resolution immunological studies that we can link to clinical data and outcome to understand pathogenesis. My group works in close collaboration with the Dep of respiratory medicine, Karolinska University Hospital and with clinical colleagues in Umeå and Lund. The three aims stand by themselves but are well integrated with each other. Each subproject is assigned to a member of my lab warranting dedication to progress of each aim of the proposal. Methods, infrastructure and collaborations are in place providing a strong platform for the commencement of the project. SIGNIFICANCE Our work generates detailed understanding of immune mechanisms at play in sarcoidosis, which is imperative for medical innovation to help patients. Our preliminary data suggest that we have identified an autoantibody in patient serum that could serve as a clinically useful biomarker of sarcoidosis. The method to analyze serum autoantibodies can be transitioned from the complex platform we have utilized to a care of point method that could readily be used by healthcare staff.