Projects / Programmes
Systemic autoimmune diseases
January 1, 2015
- December 31, 2021
| Code |
Science |
Field |
Subfield |
| 3.01.00 |
Medical sciences |
Microbiology and immunology |
|
| Code |
Science |
Field |
| B500 |
Biomedical sciences |
Immunology, serology, transplantation |
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
Systemic autoimmune diseases, autoantibodies, immunoserological assays, inflammation, acute phase proteins, atherosclerosis, vasculitis, thrombosis, rheumatoid arthritis, biologicals, epigenetics, nanotubes, systemic sclerosis, fibrosis, giant cell arteritis, patient registery
Researchers (43)
Organisations (1)
Abstract
The research program P3-0314 includes 14 projects, 6 research-oriented and 8 clinical projects (Gantt chart enclosed). While P3-0314 is a continuation of the previous program (2009-2014), we plan introduce and develop new methodologies, innovative ideas and applications.
We will use the in vitro model of the ANX A5 anticoagulant shield and atomic force microscopy to study the pathogenicity of autoantibodies isolated from patients with severe autoimmune diseases, such as catastrophic antiphospholipid syndrome that could contribute to greater understanding of micro-thromboses. Furthermore, we plan to characterize the binding of antiprothrombin antibodies to its antigen using the phage library and giant phospholipid vesicles, as well as determine their effects in cellular models. Investigation of antiprothrombin antibodies IgA could benefit diagnostics of antiphospholipid syndrome and improve evaluation of risk for thrombosis and/or pregnancy complications. Examination of inflammatory-induced epigenetic changes is important, since the renewal of normal epigenetic patterns early in disease development can be an effective way of preventing aggresive forms of chronic inflammatory diseases, such as rheumatoid arthritis, where joints are largely afflicted without therapy. Studies on implants are crucial to determine compatibility of the implanted material (TiO2) with surrounding molecules/tissues. Since inflammation can be linked to fibrosis development, we plan to investigate whether serum amyloid A could act as a marker of systemic sclerosis prognosis/organ involvement. Serum Amyloid A, an acute phase protein can cause chronic inflammation, if left unchecked. So, developing a novel method to detect multiple antibodies against acute phase proteins could screen for diagnosis/organ involvement/associated diseases. Monitoring serum levels of biological drugs and their antibodies is also our priority. Since genetic polymorphisms could influence drug efficiency we aim to evaluate polymorphisms affecting methotrexate in patients with rheumatoid and psoriatic arthritis. Our clinical studies are geared towards rheumatoid arthritis, vasculitis and ankylosing spondyloarthritis and their incidence/prevalence in Slovenia. We will evaluate whether ultrasound is a viable diagnostic tool for giant cell arteritis and will incorporate a more personalized/participatory approach into clinical practice.
In summary, the P3-0314 program group includes clinicians and other research professionals in the area of systemic autoimmune diseases, autoantibodies and inflammatory parameters, who are internationally connected. Our results are publications in SCI-cited journals, development of novel methodologies, a patent, transfer of knowledge, as well as active, long-term and successful collaborations with national and international centers. The program is important for development of the medical sciences (rheumatology, immunology, internal medicine), technical advances, education of specialists in autoimmunity and for improvement of healthcare in Slovenia.
Significance for science
Autoimmunity, inflammation, atherosclerosis and vascular diseases represent a medical priority in developed countries. However, the cross-talk between the scientific areas is still understudied and remains to a large extent unclear.
The suggested program represents a continuation of research activities of the group, with a strong emphasis on the 4 Ps in Medicine (prevention, prediction, personalization and participatory medicine), incorporation of bioinformatics/databases, such as the Registry of patients on biological medications and developing and using state of the art systems, such as a) atomic force microscopy to study pathogenic properties of autoantibodies, b) epigenetics to determine environmental regulation of the celular inflammatory transcriptome, c) research on titanium dioxide nanotubes for potential implantable devices, d) phage library and giant lipid vesicles to study antigen-antibody binding, e) scratch cellular wound healing model and antibacterial assays to study the characteristics of the acute phase protein Serum Amyloid A locally.
The following scientific milestones are planned for implementation into diagnostics/prognostics/disease progression:
Determine whether SAA can be used as a marker of organ involvement in patients with systemic sclerosis.
Multiple biomarker development: Acute phase proteins and their endogenous antibodies
Innovative method for detection of Biologicals and anti-biological antibodies
Determine whether Methotrexate therapy elevates AICAR in patients with systemic inflammatory disease and possible positive implications of metabolic pathways
Collection and curation of epidemiological data for systemic vasculitis, rheumatoid arthritis and ankylosing spondyloarthritis.
Determine whether ultrasound of the temporal artery can be positioned into the diagnostic algorithm of suspected Giant Cell Arteritis.
Significance for the country
Autoimmune diseases include more than 80 chronic illnesses, with around 20 million afflicted patients in Europe with a rising prevalence. Patients are exposed to permanent pain, reduced productivity at work, loss of organ function and early mortality. For this reason, research in this area is one of current medical priorities.
The research program P3-0314 is a part of the Department of Rheumatology, University Medical Center-Ljubljana with tight connections between the clinical, routine diagnostic and research/development environments. This kind of millieu continuously promotes exchange of information, knowledge for the benefit of innovations and current clinical needs. Optimized methods stemming from the program are directly translated to diagnostics/prognostics. Program members are involved in many international clinical studies conducted with pharmaceutical industry. The research program P3-0314 is active in many international projects and educates/mentors numerous doctoral, master's and undergraduate candidates primarily from Faculties of Pharmacy and Medicine of the University of Ljubljana. P3-0314 was awarded twice in UMC-LJ, Prof. Rozman received the Zois Life achievement award and many projects within the program received quality awards. Members of the program organized and hosted the 7th Autoimmunity Congress with more than 1600 participants and a 3-day multicenter workshop on Serum amyloid A (2010). We plan to contuinue actively participating in the organization of workshops and meetings. The program is developing/introducing many new methods and optimizations important for diagnostics and prognostics (such as in house method for aPS/PT, routine quantification of SAA, in-house isolation of beta2-GPI and anti-GPI antibodies, detection of HLAB27, one of the diagnostic markers of ankylosing spondyloarthritis, innovative detection of anti-dsDNA protiteles which yielded a patent). Our immunoserological tests are competitive, not only at the national, but also regional level. We developed an electronic registry of patients with inflammatory rheumatic diseases (ankylosing spondylitis, rheumatoid arthritis), who take biologicals for safe monitoring, which we plan to use for further national and international studies.
Most important scientific results
Annual report
2015,
interim report
Most important socioeconomically and culturally relevant results
Annual report
2015,
interim report
