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Interferon Expression Profiling as a Detection Marker in Early Systemic Lupus Erythematosus

Leest, P. van der (2017) Interferon Expression Profiling as a Detection Marker in Early Systemic Lupus Erythematosus. Master's Thesis / Essay, Biomedical Sciences.

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In recent years, there is growing interest for the interferon (IFN) signature in patients with systemic lupus erythematosus (SLE), due to diagnostic value and its link with disease activity. However, there are no generally accepted methods and study conditions to determine the IFN signature. Therefore, the initial objective in this project consisted of the selection of IFN-related transcripts, regulated by both IFN type I and type II, based on literature analysis. After transcript selection, the aim of this study is to compare the IFN signature in multiple biological substances based on a frequently used method called the IFN-score. For that reason, the RNA expression profiles of IFN-related transcripts have been measured in monocytes and PBMCs using quantitative real-time polymerase chain reaction (RT-PCR). Hereafter, the same transcripts were used to determine whether whole blood samples could be used as an easy substance to determine IFN positivity in SLE patients and patients prone to develop SLE, called incomplete SLE (iSLE). As a result, higher significance and better separation of relative expressions was found in the monocytes compared with PBMCs. Both substances display similar type I IFN-scores, which does not apply for IFN type II. The IFN-score based on the three most contributing transcripts, referred to as the 3-gene-based IFN-score, showed to be a suitable substitute for the type I IFN-score. In terms of diagnostic value, similar IFN positivity have been detected in whole blood samples compared with monocytes in iSLE and SLE patients. Altogether, for determination of positivity for the type I IFN signature is required, as is conventional in current literature, measuring the 3-gene-based IFN-score interchangeable in monocytes, PBMCs or whole blood samples would suffice. To gather more information on disease activity, pathogenesis and the predictive value of the IFN signature in SLE patients, monocytes seem to be the most reliable biological substance.

Item Type: Thesis (Master's Thesis / Essay)
Degree programme: Biomedical Sciences
Thesis type: Master's Thesis / Essay
Language: English
Date Deposited: 15 Feb 2018 08:32
Last Modified: 15 Feb 2018 08:32

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