Systemic Autoimmune Diseases
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Our research group within the Department of Rheumatology at the University Medical Center in Ljubljana has been led from 1974 to 2010 by Prof. Blaž Rozman. Our current research program entitled “Systemic Autoimmune Diseases” encompasses 2 broad areas, namely DISEASE BIOMARKERS including autoantibodies against phospholipids, microparticles and serum amyloid A and CLINICAL STUDIES focused on understanding the pathogenic mechanisms and exploring novel therapies. The basic research area includes determination of paratopes of anti-beta2 glycoprotein I antibodies with a phage library, differentiation of high and low avidity antibodies using surface plasmon resonance, as well as characterization of oxidatively modified immunoglobulin effects influencing their binding capacity and specificity. We have led an international collaborative effort in order to evaluate the avidity of anti-beta2 glycoprotein I antibodies in patients and developed a novel ELISA for improved anti-prothrombin antibody detection, both contributing to optimization of diagnostics for antiphospholipid syndrome. In collaboration with the Jožef Stefan Institute, using atomic force microscopy, we reported that pathogenic anti-annexin A5 or anti-beta2 glycoprotein I antibodies are necessary for the disruption of the protective annexin A5 crystalline shield over phospholipid surfaces. With Prof. Steffen Gay from the University of Zurich we showed that monocyte-derived microparticles impair apoptosis of rheumatoid arthritic synovial fibroblasts, while microRNA-126 increases it. This represents novel therapeutic targets. A clinical 5-year follow-up study demonstrated no involvement of anti-beta2 glycoprotein I antibodies in accelerated atherosclerosis of rheumatoid arthritic patients. Another clinical longitudinal study suggested that seasonal and H1N1 influenza vaccines have a potential to induce not only transient, but also long-term antiphospholipid antibody development in rare individuals. We introduced routine nephelometric measurement of serum amyloid A (SAA) into our diagnostic laboratory and with Dr. John Varga from Northwestern University, Chicago, we found that SAA was correlated with pulmonary involvement in systemic sclerosis indicating a possible link between inflammation and fibrosis. Anti-SAA autoantibodies were identified for the first time in blood donors and suggested to function as physiological regulators. We built a 15 partner international consortium around SAA’s roles in inflammation and infections, as well as organized a 3-day workshop. The most important event to date has been the co-organization of the 7th International Congress on Autoimmunity, 2010 in Ljubljana with Prof. Yehuda Shoenfeld. We developed a registry for Biological medications as well as participate in the registry for Pediatric-antiphospholipid syndrome. Our group is also a partner in an EU-sponsored project called EUMUSC, dealing with musculoskeletal disorders. On average, we publish 20 papers per year in SCI-cited journals, book chapters and guidelines for clinicians as well as patients. We believe the strengths of our research program lie within the connectivity of the clinical, routine diagnostic and research environments and we plan to build upon them in the future.
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