Immune-mediated diseases (IMIDs) are an increasing medical burden in industrialized countries worldwide. IMIDs are characterized by an enormous heterogeneity with regard to disease outcome and response to targeted therapies, which currently cannot be adequately anticipated to tailor individual patient management. Hence, mechanistic understanding of this heterogeneity and biomarkers predictive for disease control and therapy response over time are important prerequisites of a future precision medicine in IMIDs. ImmUniverse has been formed as a European transdisciplinary consortium to tackle these unmet needs and to understand the role of the crosstalk between tissue microenvironment and immune cells in disease progression and response to therapy of two different IMIDs: ulcerative colitis and atopic dermatitis. Following this unique cross-disease approach ImmUniverse will fill the gap and the limitations of current studies, which do not systematically compare the complex interactions between recirculating immune cells and the respective tissue microenvironment. The consortium will combine analysis of tissue-derived signatures with “circulating signatures” detectable in liquid biopsies, employing state-of-the-art profiling technologies corresponding to multi-Omics datasets. The project will also bring diagnostics in IMID to a new level by implementing disruptive non-invasive liquid-biopsy methodology in combination with novel, validated circulating biomarker assays which are expected to improve diagnosis, inform early in the clinical course on disease severity and progression and enable treatment response monitoring. The identified signature will be validated to monitor state/progression and response to therapy in prospective observational cohorts. Realization of these objectives will result in improvement of patient management, lead to increased patient well-being and will significantly reduce the socioeconomic burden of these diseases.

In line with IMI2 goals for improved therapies and precision medicine, the aim of this proposal is to prevent and treat RA or its progression by inhibiting maturation/expansion of pathogenic autoimmune responses through immune tolerising treatments of subjects not only in early stages of joint inflammation (undifferentiated arthritis and early RA) but also in even earlier defined stages i.e. before onset of joint inflammation, when patients have arthralgia and/or bone loss, or sub-clinical stages of joint inflammation. Today, no drugs are approved for these early phases of RA development, where symptoms such as pain and fatigue cause major loss of life quality and where successful interference would prevent onset of disease. Thus, an important part of our work will be to achieve a better understanding of this as yet unexplored phase of disease. In the proposed project we will develop and validate new methods to identify individuals at high risk for RA, tools to monitor disease progress and expand and further develop cohorts suitable for these purposes. Furthermore we will validate and standardise methods to monitor immune tolerance to be used in clinical trials for tolerising therapies for RA. The aim is thus to interfere with the specific immune reactions that contribute to RA symptoms in such a way that a specific and long-lasting therapeutic effect (ultimately a cure) is accomplished for a major proportion of RA patients and prevention of diseases is accomplished in individuals at high risk for RA. Investigator-initiated as well as company-sponsored clinical trials in well stratified patient groups will be performed in collaboration with SMEs and/or contributing pharma companies and their immune effects studied using the same panel of biomarkers allowing for standardisation across protocols. Our ambition is also to disseminate our experiences from RA to other rheumatic and other immune-mediated diseases.

Strongly associated with the epidemics of obesity and type 2 diabetes that are testing healthcare systems worldwide, Non-Alcoholic Fatty Liver Disease (NAFLD) is an increasingly common cause of advanced liver disease that is characterized by substantial inter-patient variability in severity and rate of progression. It is currently assessed by liver biopsy, an invasive, costly and risky procedure. The lack of noninvasive biomarkers has hampered patient care and impeded drug development by complicating conduct of clinical trials.The overarching aim of LITMUS is to develop, robustly validate and advance towards regulatory qualification biomarkers that diagnose, risk stratify and/or monitor NAFLD/NASH progression and fibrosis stage. This will be achieved through a goal-oriented, tri-partite collaboration delivering a definitive and impartial evaluation platform for biomarkers, bringing together: (i) End-users of biomarker technologies (clinicians with expertise in NAFLD and the pharmaceutical industry)? (ii) Independent academics with expertise in the evaluation of medical test/biomarker performance? and (iii) Biomarker researchers and developers (academic or commercial). LITMUS has the demonstrable capability to fulfil the IMI call remit. Built upon foundations laid by the EU-funded FLIP/EPoS projects and long-established, successful scientific collaborations amongst many of Europe’s leading clinical-academic centres, LITMUS is at a unique advantage due to its existing large-scale patient cohorts, bioresources and multi-omics datasets. Consortium members are internationally recognised experts with substantial relevant expertise supporting the program’s clear focus on biomarker identification, validation and accelerating EMA/FDA qualification. Thus, LITMUS is powered to provide clarity on biomarker validity for NAFLD at scale and pace: supporting drug development and the targeting of medical care and limited healthcare resources to those at greatest need.