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Monitoring innate immunity in arthritis and mucosal inflammation

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Novel biomarkers for inflammatory disorders

Prompt diagnosis and monitoring of joint arthritis poses a significant medical challenge. To address this, European researchers developed novel diagnostic tools and identified molecular targets for direct therapeutic interventions.

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Chronic inflammatory diseases are not always associated with autoimmunity and the presence of autoreactive antibodies. Such seronegative types of joint diseases frequently present extra-articular manifestations in epithelial tissues like skin and gut. Accumulating evidence also supports a role for innate immunity as well as environmental triggers in disease development for genetically susceptible individuals. Following initial activation of both innate and adaptive immunity, various effector mechanisms such as cytokines and damage-associated molecular pattern (DAMP) molecules contribute to the on-going inflammation. The diagnosis and care of affected individuals is extremely challenging, necessitating novel tools and biomarkers. In this context, the EU-funded MIAMI (Monitoring innate immunity in arthritis and mucosal inflammation) project was directed to achieving better diagnostic tools and novel targets for pharmaceutical therapies to significantly improve patient care in seronegative arthritis. Their work focused on therapeutically targeting S100 proteins, the pro-inflammatory members of the DAMP-family, for chronic inflammatory diseases of gut and joint. Among the key findings of the study was the identification of S100-DAMPs as contributors of disease development in different animal models of seronegative arthritis and in the acute state of bowel inflammation. In addition, these molecules served as reliable serum biomarkers in mice for the quantification of local disease. Since their precise mechanism of function remains unknown, further investigation into the biology of these molecules is required in different disease settings. In addition to providing S100 cut-off levels, researchers discovered that phagocyte-specific S100 proteins could be used for predicting local inflammatory processes. To support early diagnosis of chronic joint and gut inflammation, they defined the innate inflammatory response patterns in joint and gut through extensive analysis of cytokines, the transcriptome and the proteome. Apart from fundamental insight into seronegative inflammatory conditions, the cutting-edge research performed during MIAMI led to the development of proprietary point-of-care tests for easy and unrestricted use in the clinic.

Keywords

Joint arthritis, DAMP, biomarker, MIAMI, S100

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