Aim of this study is to determine the role of Trained Immunity in the pathogenesis of Still’s disease, and the therapeutic potential of inhibiting this mechanism for the treatment of this condition. Several factors are ideally aligned to achieve these ambitious research goals: a large cohort of patients with Still’s disease, an optimal experimental platform, and a synergistic enterprise with world-leading experts in the field.
Project LeadG Cavalli
In order to test the hypotheses the following aims are proposed:
Ferrero E, Villa A, Stefanoni D, Nemkov T, D'Alessandro A, Tengesdal I, Belloni D, Molteni R, Vergani B, De Luca G, Grassini G, Cangi MG, Dagna L, Doglioni C, Cavalli G, Ferrarini M. Immunometabolic activation of macrophages leads to cytokine production in the pathogenesis of KRAS-mutated histiocytosis.. Rheumatology (Oxford). 2022 Apr 11;61(4):e93-e96. doi: 10.1093/rheumatology/keab869.PMID: 34919661
Molteni R, Biavasco R, Stefanoni D, Nemkov T, Domínguez-Andrés J, Arts RJ, Merelli I, Mazza D, Zambrano S, Panigada M, Cantoni E, Tengesdal IW, Maksud P, Piras F, Cesana D, Cassina L, Distefano G, Loffreda A, Gnani D, De Luca G, Tomelleri A, Campochiaro C, Joosten LAB, Dinarello CA, Kajaste-Rudnitski A, Haroche J, Cardaci S, Cenci S, Dagna L, Doglioni C, Ferrarini M, Ferrero E, Boletta A, D'Alessandro A, Montini E, Netea MG, Cavalli G. Oncogene-induced maladaptive activation of trained immunity in the pathogenesis and treatment of Erdheim-Chester disease. Blood. 2021 Oct 28;138(17):1554-1569. doi: 10.1182/blood.2020009594.PMID: 34077954
Cavalli G, Tengesdal IW, Gresnigt M, Nemkov T, Arts RJW, Domínguez-Andrés J, Molteni R, Stefanoni D, Cantoni E, Cassina L, Giugliano S, Schraa K, Mills TS, Pietras EM, Eisenmensser EZ, Dagna L, Boletta A, D'Alessandro A, Joosten LAB, Netea MG, Dinarello CA. The anti-inflammatory cytokine interleukin-37 is an inhibitor of trained immunity. Cell Reports. 2021 Apr 6;35(1):108955. doi: 10.1016/j.celrep.2021.108955.PMID: 33826894
This study is important to many patients with AOSD and SJIA, and many already volunteered to donate samples. In collaboration with AMRI (a non-profit patient organisation with investment in SD) there is a strong engagement of patients in the research process.
Regular updates on research findings, instructions on research strategies based on patients’ insight, and development for shared initiatives for effective dissemination of findings to societal stakeholders will be provided.