Knowledge Resource Center for Ecological Environment in Arid Area
| Biomarkers of disease activity and organ damage in systemic lupus erythematosus | |
| Wirestam;Lina | |
| 出版年 | 2017 |
| 学位授予单位 | Linköpings universitet, Avdelningen för neuro- och inflammationsvetenskap, Linköpings universitet, Medicinska fakulteten, Linköping |
| 英文摘要 | Systemic lupus erythematosus (SLE) is a systemic inflammatory disease. Clinically, the distinction between ongoing inflammation attributed to SLE, and organ damage due to medication or co-morbidities remains challenging. In addition, SLE is a heterogeneous disease where the various disease phenotypes complicate the search for biomarkers that adequately reflect disease activity and/or signs of increasing organ damage. The aim of the thesis was to investigate and evaluate potential new biomarkers of disease activity and/or organ damage in SLE patients. High mobility group box protein-1 (HMGB1) is a nuclear non-histone protein that can shuttle to the cytoplasm, become secreted extracellularly, and participate in systemic inflammation. Administration of monoclonal anti-HMGB1 antibodies has been reported both to attenuate and intensify disease in animal models of arthritis and lupus. In Paper I of the thesis, circulating anti-HMGB1 was found in 23% of the SLE patients and correlated with disease activity variables. The biological role of these autoantibodies remains to be elucidated. As a consequence of massive circulating levels of cellular debris and immune complexes, SLE patients have insufficient capacity to remove such material via the reticuloendothelial system. Pentraxin 3 (PTX3) may possibly protect against lupus flares due to classical complement activation, opsonization of apoptotic cells, and cytokine induction. In Paper II, circulating PTX3 was found to be inhibited or exhausted by interferon (IFN)-α, a key cytokine of SLE pathogenesis, and serum levels of PTX3 in SLE patients were inversely related to IFN-α levels. Suppressed PTX3 levels may contribute to a vicious circle resulting in impaired waste clearance, autoantigen exposure and autoantibody production, and sustained disease activity. Osteopontin (OPN), a protein known to influence cell signaling and apoptosis, has been proposed as a marker of organ damage in pediatric lupus. In a Swedish cross-sectional study, circulating OPN levels were found to be raised in SLE (Paper III). In patients with recent-onset disease, OPN reflected disease activity, while in established disease, OPN appeared to mirror damage accrual and cardiovascular damage. In Paper IV, OPN was instead analyzed in an international longitudinal multi-center study based on patients with recent-onset SLE and follow-up data. OPN turned out to be a poor predictor of organ damage, but significant associations were observed between OPN and disease activity both at disease onset, as well as over 5 years of follow-up. In conclusion, increased anti-HMGB1 antibody and decreased PTX3 levels could potentially sustain the impaired waste-disposal. Of the molecules analyzed in this thesis, OPN seems to be the best marker of disease activity. Further studies of these proteins may help to better understand SLE pathogenesis and to optimize treatment of patients. |
| 英文关键词 | Rheumatology and Autoimmunity Reumatologi och inflammation Gastroenterology and Hepatology Gastroenterologi Immunology in the medical area Immunologi inom det medicinska omr?det Neurology Neurologi |
| 语种 | 英语 |
| URL | http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-140713 |
| 来源机构 | Linköpings universitet |
| 资源类型 | 学位论文 |
| 条目标识符 | http://119.78.100.177/qdio/handle/2XILL650/250945 |
| 推荐引用方式 GB/T 7714 | Wirestam;Lina. Biomarkers of disease activity and organ damage in systemic lupus erythematosus[D]. Linköpings universitet, Avdelningen för neuro- och inflammationsvetenskap, Linköpings universitet, Medicinska fakulteten, Linköping,2017. |
| 条目包含的文件 | 条目无相关文件。 | |||||
| 个性服务 |
| 推荐该条目 |
| 保存到收藏夹 |
| 导出为Endnote文件 |
| 谷歌学术 |
| 谷歌学术中相似的文章 |
| [Wirestam;Lina]的文章 |
| 百度学术 |
| 百度学术中相似的文章 |
| [Wirestam;Lina]的文章 |
| 必应学术 |
| 必应学术中相似的文章 |
| [Wirestam;Lina]的文章 |
| 相关权益政策 |
| 暂无数据 |
| 收藏/分享 |
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。
