RELENT (RELapse PrevENTion in autoimmune disease: mechanisms and co-morbidities) is a multidisciplinary consortium that was formed to meet the objectives of Horizon 2020 PHC 3 – 2015, namely to identify mechanisms that were common to a number of different diseases and had important effects on clinical outcome. RELENT’s work focussed on severe autoimmune and inflammatory diseases, including some of the most disabling chronic diseases that can affect individuals of all ages and both sex and can cause severe injury to many organs; like rheumatoid arthritis, inflammatory bowel disease and various forms of vasculitis. Management of these diseases is difficult and typically includes long-term treatment with powerful immunosuppressive and anti-inflammatory drugs and therapeutic monoclonal antibodies. These drugs can be associated with severe side effects and despite recent advances the outlook for many patients with these diseases is worse than for many cancers, many patients become severely disabled or die prematurely either from the diseases themselves or from complications of the drugs. These chronic diseases present a severe challenge for patients throughout Europe as well as for the physicians who care for them and healthcare delivery systems that provide the resources to do so. Currently there is an urgent need for better strategies to tailor drug treatment to the individual needs of patients but this requires deeper knowledge of the immune and inflammatory pathways that cause the injury: this is what the RELENT Consortium was assembled to provide.
The RELENT investigators have used a group of related diseases that cause inflammation of blood vessels (vasculitis) to model chronic immune mediated inflammatory diseases more generally. In particular, much of the work focussed on one of the commonest forms of vasculitis, ANCA-associated vasculitis (AAV), so-called because it is caused by autoimmunity to one of two proteins expressed in the cytoplasm of neutrophils (white blood cells), namely myeloperoxidase (MPO) and proteinase-3 (PR3). AAV was chosen because it is relatively homogeneous and sufficiently well understood to provide the foundation for deeper analysis of inflammatory pathways, and because members of the consortium had previously shown it could be used to identify pathogenic pathways that were shared with other diseases. The consortium consisted of 13 Partners (9 from academia and 4 from industry) including geneticists, biochemists, cell biologists and clinical investigators with specific expertise in AAV and related disorders, as well as expert patients with these diseases. The work combined genetic and proteomic analysis of patient cohorts with cellular and animal models of disease separated into four interrelated Work Packages.
