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Theses, dissertations and research publications (including journal articles, conference abstracts and books) from Lund University are collected in this database. Where possible, the option to download a full text document is available. It is also possible to search for Lund University student theses in the student theses database.
| Title | On the immunopathogenesis of systemic lupus erythematosus - Immune complexes, type I interferon system, complement system and platelets |
| Author/s | Christian Lood |
| Department/s |
Department of Rheumatology
|
| Full-text | Available as PDF |
| Defence date | 2012-05-16 |
| Defence time | 09:00 |
| Defence place | BMC D15, Belfragesalen |
| Opponent | Professor Dror Mevorach |
| Publication/Series | Lund University, Faculty of Medicine Doctoral Dissertation Series |
| Publishing year | 2012 |
| Volume | 2012:32 |
| Pages | 84 |
| Document type | Dissertation |
| Language | English |
| Publisher | Section of Rheumatology, Dept of Clinical Sciences, Lund |
| Abstract English |
Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disorder characterized by inflammation in several organ systems. SLE patients have an impaired ability to clear dying cells which leads to the exposure of several nuclear antigens which might break self tolerance. Autoantibodies directed against the nuclear antigens will form large immune complexes (ICs) which are central in the immunopathogenesis of SLE. Through activation of the complement system, ICs mediate tissue destruction, and through interaction with immune cells ICs induce large amounts of pro-inflammatory cytokines, including IFN-alpha. Furthermore, ICs might activate platelets and thus be involved in the development of cardiovascular diseases which is increased in SLE patients. In this thesis I have investigated the immunopathogenesis of SLE with an emphasis on ICs, type I interferon (IFN) system, complement system and platelets. In the first papers we studied the plasmacytoid dendritic cell (pDC) and properties regulating their IFN-alpha producing ability, a central cytokine in the SLE pathogenesis. We found that C1q, a component of the classical pathway of the complement system, could regulate the type I interferon production by pDCs (Paper I). Furthermore, pDCs were able to produce a pro-inflammatory protein, S100A8/A9, which is increased in SLE patients (Paper II). Next we observed that the complement system and type I IFN system affect the platelets. Platelets isolated from SLE patients were more activated, had a type I IFN signature (Paper III), as well as complement deposition on the cell surface (Paper IV). Both the type I IFN signature and the complement deposition were associated with cardiovascular disease and venous thrombosis. In the final paper we found that EndoS, a bacterial endoglycosidase, abolished all pro-inflammatory properties of ICs isolated from SLE patients (Paper V). Thus, we suggest that EndoS has the potential to be developed as a new therapy against SLE considering its potent IC-modulating effects. In summary, this thesis confirms a central role of immune complexes and their subsequent pro-inflammatory effects in the immunopathogenesis of SLE and development of cardiovascular disease and venous thrombosis. |
| Subject |
Medicine and Health Sciences |
| Keywords | autoimmunity, systemic lupus erythematosus, rheumatology, immunology, cardiovascular disease |
| ISBN/ISSN/Other |
ISSN: 1652-8220 ISBN: 978-91-86871-94-9 |
| Supervisor | Anders Bengtsson |
| Supervisor | Lennart Truedsson |
| Supervisor | Gunnar Sturfelt |
| Part of | C1q inhibits immune complex-induced interferon-alpha production in plasmacytoid dendritic cells: A novel link between C1q deficiency and systemic lupus erythematosus pathogenesis. |
| Part of | Protein synthesis of the pro-inflammatory S100A8/A9 complex in plasmacytoid dendritic cells and cell surface S100A8/A9 on leukocyte subpopulations in systemic lupus erythematosus |
| Part of | Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease. |
| Part of | IgG glycan hydrolysis by EndoS diminishes the pro-inflammatory properties of immune complexes from patients with SLE - a possible new treatment? |
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