MIAMI

Monitoring innate immunity in arthritis and mucosal inflammation

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 Obiettivo del progetto (Objective)

'In chronic joint disease, only a subgroup of patients has classical autoantibodies, while the other variants are seronegative arthritis syndromes with a predominance of innate immune disturbances. These forms of joint diseases frequently show extra-articular manifestations of epithelial tissues like skin and gut. On the molecular level, innate immune activation and the release of damage associated molecular pattern proteins (DAMPs) of the S100 family are important mechanisms of initiation and perpetuation. Early diagnosis remains a significant problem, and prediction of disease extension and course is challenging. Despite all efforts we do not have therapies that alleviate the disease and protect from disease progression, damage and long-term disability. The identification of specific inflammatory mechanisms that correlate to patterns of disease characteristics would allow targeted therapeutic approaches. In a comprehensive research approach, MIAMI will establish relevant disease mechanisms and translate finding into novel biomarkers for individual adaptation of therapies (personalised medicine) for seronegative arthritis. Our research strategy leaves retracted ways of genetics and classical autoimmunity; instead we will focus on innate immunity and inflammation. The goals of MIAMI are ambitious and will be reached with cutting-edge research performed by the most excellent researchers in the field, who have been combined to form a multidisciplinary consortium. The choice of the scientific as well as industry partners was entirely based on excellence. Thus, MIAMI brings together the leading teams that are working on mechanisms of innate immunity in arthritis and mucosal inflammation. In summary, MIAMI will significantly contribute to progress on the key questions: Who will be affected by which disease manifestation or complication, how can we use this knowledge to identify the disease, and what will be a meaningful target to treat or even prevent deleterious outcome.'

Introduzione (Teaser)

Early diagnosis of joint arthritis remains a significant problem, and prediction of disease progression and course is challenging. The identification of disease biomarkers should help in this respect.

Descrizione progetto (Article)

Chronic inflammatory disorders of the joints are not necessarily associated with autoimmunity. Emerging evidence clearly shows that a number of patients with inflammatory arthritis suffer from disturbed innate immune responses and have no presence of autoimmune antibodies.

Currently, there are no therapies that alleviate the disease and protect from disease progression, damage and long-term disability. As a result, it is important to delineate the specific mechanisms that correlate with inflammatory disease in order to design more effective and targeted therapeutic approaches.

The scope of the EU-funded 'Monitoring innate immunity in arthritis and mucosal inflammation' (http://www.miamiproject.eu/ (MIAMI)) project is to consolidate existing biomarkers and develop novel ones for personalised therapy in non-autoimmune arthritis. Preliminary study results indicate that innate immune activation is associated with the release of damage-associated molecular pattern proteins of the S100 family. In both patients and experimental models, these molecules seem important for disease initiation and progression.

Key project activities also include the development of novel methodologies for efficient and early diagnosis of chronic joint and gut inflammation. MIAMI partners will associate S100 proteins with disease stage and identify which of these could serve as biomarkers for populations at risk and those with progressive disease. Following extensive cytokine, transcriptomic and proteomic analyses, scientists hope to identify novel biomarkers as well for monitoring local inflammation and disease progression.

With the help of participating small and medium-sized enterprises, MIAMI hopes to translate these findings into clinically validated assays. Coupled with biomarker identification, the activities of the MIAMI study should identify new disease targets for treating or even preventing deleterious outcomes.