Abstract
Inflammation has a key role in the pathogenesis of various human diseases. The early detection, localization and monitoring of inflammation are crucial for tailoring individual therapies. However, reliable biomarkers to detect local inflammatory activities and to predict disease outcome are still missing. Alarmins, which are locally released during cellular stress, are early amplifiers of inflammation. Here, using optical molecular imaging, we demonstrate that the alarmin S100A8/S100A9 serves as a sensitive local and systemic marker for the detection of even sub-clinical disease activity in inflammatory and immunological processes like irritative and allergic contact dermatitis. In a model of collagen-induced arthritis, we use S100A8/S100A9 imaging to predict the development of disease activity. Furthermore, S100A8/S100A9 can act as a very early and sensitive biomarker in experimental leishmaniasis for phagocyte activation linked to an effective Th1-response. In conclusion, the alarmin S100A8/S100A9 is a valuable and sensitive molecular target for novel imaging approaches to monitor clinically relevant inflammatory disorders on a molecular level.
Highlights
Inflammation has a key role in the pathogenesis of various human diseases
During the activation of these cells, S100A8/S100A9 complexes are locally released in virtually all inflammatory disorders that are associated with phagocyte activation, like autoimmune diseases, rheumatoid arthritis, allergies, cardiovascular diseases, or local and systemic infections and tumours[7], whereas virtually no expression can be found in healthy tissue
Using fluorescence reflectance imaging (FRI), we provide the first evidence that molecular imaging allows for the reliable detection of S100A8 and S100A9 in preclinical models, locally expressed during disease, and that visualization of these proteins in conjunction with further laboratory analysis enables the monitoring of local inflammation with unique sensitivity, even allowing for the detection of sub-clinical, residual disease activity
Summary
Inflammation has a key role in the pathogenesis of various human diseases. The early detection, localization and monitoring of inflammation are crucial for tailoring individual therapies. In vivo visualization of local inflammation has been performed, for example, using F-18-fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET) or magnetic resonance imaging (MRI) with or without contrast enhancement[2] These methods have proven diagnostic value, their implication in clinical practice has not fostered personalized therapy, mostly due to a lack of either desirable specificity (PET) or sensitivity (MRI). Targeted imaging approaches to overcome these limitations would ideally address a biomarker with high expression/release or accumulation locally at the site of inflammation, representative of early inflammatory processes and residual disease activity or a prediction of flare-ups of disease in remitting-relapsing courses of chronic inflammation. Serum concentrations of S100A8/S100A9 complexes have been shown to be superior over conventional biomarkers for the monitoring of inflammatory disorders, especially in the detection of residual disease activity and in the prediction of relapse in arthritis[12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
