Projects / Programmes
Immune and genetic markers and their impact on early detection and targeted treatment of systemic lupus erythematosus and related conditions.
| Code |
Science |
Field |
Subfield |
| 3.01.00 |
Medical sciences |
Microbiology and immunology |
|
| Code |
Science |
Field |
| B660 |
Biomedical sciences |
Pediatrics |
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
Systemic lupus erythematosus, vaccination, inherited immune deficiencies, autoimmunity
Researchers (19)
Organisations (2)
Abstract
Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disorder with a broad clinical spectrum, unpredictable course and many life threatening manifestations. Proposed research project consist of three parts:
Adding insight into the mechanisms of failure of peripheral tolerance in patients with SLE including expansion of autoreactive T cells. In this part, we will investigate intracellular STAT signaling and associated cytokine signaling in peripheral blood CD4+T cells including regulatory T cells in patients with SLE. Flow cytometry based methods that allow better molecular definition of novel effector T cell and Treg subsets and specific analysis of signaling events also in ex vivo Treg cells by combining detection of intracellular Foxp3 expression with (phospho) STAT-proteins will be used. Our preliminary results indicate that using such novel methods imbalanced STAT signaling associated with perturbed homeostasis between pathogenic – conventional CD4+ efector T cells and Tregs can be identified. Such perturbed signaling may predispose patients to more aggressive disease and could therefore serve as biomarker of disease severity. In addition to such novel diagnostic tools, results of our study could also identify new targets of more specific and less toxic therapy for SLE within STAT signaling pathways, which could selectively affect expansion and survival of pathogenic-conventional T cells and at the same time improve homeostasis and regulatory T cell function.
Evaluate mechanisms of immune response after vaccination in patients with SLE including analysis of safety and efficacy of vaccination. In this part, we will evaluate long term safety and efficacy of varicella vaccination in patients with systemic autoimmune diseases treated with immunosupressive and/or biologic therapy. Disease activity, protective antibodies and T cell response will be followed after vaccination. Production of gamma-interferon by T memory cells upon in vitro stimulation with virus antigen will be measured. It is assumed that in patients with autoimmune diseases treated with immunosuppressive and/or biologic therapy, protective antibodies after vaccination decline faster as in healthy persons.
Evaluate immunopathogenesis of development of systemic autoimmune diseases resembling SLE, which could occur in patients with inherited monogenic defects in the immune system function. Research will include patients with primary immunodeficiency (PID) from Slovene PID registry where we are planning to collect data on autoimmune diseases. Immune and genetic investigations will be performed to identify immune and genetic factors in patients with SLE-like disease and other autoimmune diseases. From clinical data of a large cohort of patients with chronic granulomatous disease from Central and Eastern Europe we will extract data regarding inflammatory and autoimmune complications, treatment options and influence on morbidity and mortality of the patients. Collected data will help us determine the influence of excessive inflammation and autoimmunity in patients with chronic granulomatous disease and will help us improve understanding of the inflammatory pathways in systemic autoimmune diseases resembling SLE.
Our proposed project is clinically focused with two main objectives including development of better diagnostic ability for early identification of patients with SLE and similar conditions and recognition of patients with SLE that have worse long-term outcome and impact of treatment on the long-term outcome. All methods that will be used in the proposed project were already introduced and established in our laboratories and were used in our previously published studies. In this project we will include pediatric patients with SLE followed at the University Children’s Hospital Ljubljana, adult patients with SLE, followed at the rheumatology department, University Medical Center Maribor, and patients with PID from Slovenia and Central-East
Significance for science
Our research proposal is focused on systemic immune-mediated diseases which are one of the most common chronic disorders in pediatric population. Our studies are clinically focused with two main objectives including development of better diagnostic ability for early identification of patients with different systemic immune-mediated diseases and recognition of patients with systemic-immune mediated disease that have worse long-term outcome and impact of treatment on the long-term outcome. As a whole the project may support the link between the innate immunity responses and the clinical manifestations of the systemic autoimmune diseases and could point to new targets of more specific and less toxic therapy in these diseases.
Significance for the country
The research proposal is clinically focused and is aimed to improvement of health care including development of new clinical and laboratory diagnostic protocols and more targeted treatment of systemic autoimmune diseases.
Most important scientific results
Interim report,
final report
Most important socioeconomically and culturally relevant results
Final report
