Systemic Autoimmune diseases

Our research program P3-0314 encompasses rheumatologists, pulmonologists, neurologists, gastroenterologists, biochemists, pharmacists, molecular/cell biologists, biostaticians/bioinformaticians, laboratory experts, economists and patients groups. Activities are predominantly geared towards optimization of therapy/drug repurposing, elucidation of disease mechanism for inflammatory rheumatic disease (IRD), novel therapeutic targets and utilization of autoantibodies/biomarkers for earlier diagnostics/prognostics, disease activity and organ involvement. We will introduce comprehensive treatment for patients with IRD, with the aim of achieving lifestyle improvement and developing an effective, financially sustainable model. We will gain detailed insight into pharmacokinetics of biologics in a real clinical setting, helping physicians make better treatment decisions, with a personalized/cost-effective approach. Using precision medicine, we will deepen our understanding of fibrotic mechanisms targeting metabolism, that could lead to new/better therapeutic strategies in systemic sclerosis. Research on anti-SAA1 antibodies could contribute to an innovative approach in treating hyperinflammation that can occur in COVID-19, as well as other diseases (e.g. macrophage activation syndrome, catastrophic antiphospholipid syndrome, septic shock). Systemic vasculitis usually presents as an emergency in rheumatology due to multi-organ involvement/risk of vital organ failure. We will integrate extensive data from multidimensional technologies with high resolution e.g. single-cell RNA sequencing, high-dimensional flow cytometry, ATAC sequencing, epiMethylTag analysis, curated molecular/cellular/clinical data, to build knowledge-based prediction models using machine learning algoritms/artificial inteligence. This will enable identification of most vulnerable patients at earlier time points. We will collaborate in developing (with Institute Jozef Stefan and University of Ljubljana-Faculty of Electrical Engineering) a biomimetic approach to higher quality materials/applications for patient implants. From an economic point of view, we will explore the dilemma of including the cost of productivity losses in the economic evaluation of health technologies for patients with IRD. With the improvements of biorx.si (a tool for capturing high quality data in clinical practice) we will obtain more complete, higher-quality, richer data, without a major burden to rheumatologists. The new, original biorx.si design will allow faster adaptations to new challenges. Our program, P3-0314 (2022-2027) will strive for lowering the substantial personal, social and healthcare burdens of systemic autoimmune diseases, including IRD, while providing the highest possible quality of care and standards to our patients.

Systemic autoimmune diseases, including inflammatory rheumatic diseases (IRD) cover ?80 chronic conditions, with around 20 million cases in Europe and an increasing prevalence. Patients can be exposed to persistent pain, reduced ability to work, loss of organ function, disability and early mortality. Therefore, research in this area is one of the continuous medical priorities. Nevertheless, scientific fields studying systemic autoimmune diseases and IRD are still insufficiently connected and underexplored. Our national research program P3-0314 will continue investigating IRD and other systemic autoimmune diseases with a strong emphasis on 4P medicine (preventive, predictive, personalized and participatory) with a precision approach, bioinformatics tools, registries, and databases. We will bring together clinical sciences, molecular and cell biology, biochemistry, pharmacy, chemistry, physics, electrical engineering, economics, biostatistics, machine learning and artificial intelligence, in order to acquire new knowledge. High dimensional flow cytometry, single cell RNA sequencing, ATAC sequencing and epiMethylTAG analyses will provide high resolution data that will enable, together with highly specialized knowledge from companies, such as BIA Separations/Sartorius (monolithic chromatography) and Nanoview Biosciences (Exoview technology for exosomal markers), the development of new state-of-the-art models/systems such as: a) predictive response model to inflammatory arthritis treatment based on the integration of clinical, imaging, high-dimensional laboratory, cellular and molecular data. b) an efficient and financially sustainable model of integrated comprehensive treatment of IRD patients c) verification of the usefulness of monitoring biologics and their autoantibodies in the newly developed subcutaneous formulation/application of infliximab and vedolizumab d) use of natural anti-SAA1 autoantibodies to silence the cytokine storm e) an innovative approach to modify currently used stent materials f) a new original design of the national, multicenter biorx.si registry, which contributes data along with other international groups (from Finland, Norway, Denmark, Netherlands, Spain, Czech Republic and Russia) evaluating the effectiveness of treatment strategies for rheumatoid arthritis (CERRERA, TOCERRA, JAK-pot) and spondyloarthritis (EuroSpA) Thus, we plan, during 2022-2027, to continue publishing in highly cited, quality scientific journals, such as Annals of The Rheumatic Diseases, Nature Communications, The Lancet, European Heart Journal, Autoimmunity Reviews, Journal of Autoimmunity, Rheumatology, as well as implement the results of P3-0314 into clinical and laboratory practice.

The national research program P3-0314 has the main and overall aim of improving health and care of patients with systemic autoimmune diseases. The program is important for the development of medical sciences (rheumatology, immunology, internal medicine), technical levels and for the education of young clinical and scientific experts in the field of autoimmunity in Slovenia. P3-0314 includes physicians, nurses, laboratory professionals, technical staff, and researchers, and closely connects the clinic and routine diagnostic laboratory with research aimed at developing improvements and innovation. As a whole, the program contributes to and exhibits priorities in the following aspects important for the socio-economic development of Slovenia: 1. multidisciplinary approach. P3-0314 collaborates with multiple clinical and research centers in SI, EU and USA, with expertise/technologies that accelerate development, integration, transfer of knowledge and research innovation. Our priorities will be patent and project applications at the Slovene, European and US levels, such as terciary projects UMCL, ARRS projects, ERC, MC, ESF, Eureka Eustars, Bill Gates Foundation. Cooperation will strengthen our collaborations with Slovenian Universities and hospitals, namely UP-FAMNIT, UL-FFA, UL-EF and OB Valdoltro, with whom we have had long-term collaborations, as well as our industry partner BIA Separations/Sartorius and with patient organizations, such as the Slovenian Association of Rheumatic Patients and the Slovenian Association of Healthcare Professionals in Rheumatology. 2. education. For P3-0314 education is key for continuous knowledge transfer, both vertically and horizontally. We educate a) doctoral students, master's and undergraduate students through mentoring and lectures, as well as b) professional staff, through workshops, conferences, online lectures, including transferable knowledge. 3. co-organization of congresses/organization of workshops. Members of P3-0314 will co-organize the International Congress on Autoimmunity and organize annual 1-day workshops aimed at presenting the most innovative work of the previous year within the participating groups of P3-0314. 4. application of knowledge. Continual transfer of knowledge is conducted from P3-0314 to the Laboratory of immunology, for measurement of (among others) SAA, aPS/PT, anti-SAA1/2, anti-SAA1, biologics (e.g. adalimumab, infliximab) and their autoantibodies, anti-SARS-CoV-2, anti-IFN?, anti-IL-6. 5. writing manuals, professional instructions and recommendations for doctors and patients. Clinical members of P3-0314 are providing, in Slovenia and within the EU (EU-MUSC Standards of care) professional manuals for clinicians as well as recommendations for patients. 6. activities in working, task force, groups. P3-0314 members are active in working groups e.g. EMEUNET ("working group of young clinicians and researchers in rheumatology"), which is part of the European League against rheumatism (EULAR) and EUSTAR (multicenter, international consortium on Systemic sclerosis). 7. communication with the public, in form of radio/TV events, invited lectures, professional and scientific contributions and popular articles.