Identification of Etanercept Responsive Biomarkers in Rheumatoid Arthritis

Student thesis: Master thesis (including HD thesis)

  • Jacob Skallerup Andersen
Introduction: Rheumatoid arthritis (RA) causes inflammation of the joints which if left untreated or inadequately treated may result in joint- and bone destruction and facilitate development of systemic co-morbidities such as cardiovascular diseases and inflammatory lung diseases. The introduction of bDMARDs have revolutionized the treatment options for RA. One of these bDMARDs is etanercept, a fusion protein made by genetic recombination. Etanercept works as a decoy receptor for TNF-a resulting in decreased cellular signaling from TNF-a binding to its target receptor. However, about 30% to 40% of RA patients do not achieve remission or low disease activity in response to treatment with anti-TNF-a treatment.

Aim: The aim of this study was to investigate the effects of long-term treatment of RA with etanercept and to identify biomarkers to monitor treatment response in these patients.

Methods: Serum samples collected from 12 etanercept-treated RA patients before treatment, and after three, six, and 12 months of treatment, respectively were analyzed proteomically by LC-MS/MS and analyzed by quantification of cfDNA levels.

Results: 79 proteins were found to have a significantly altered abundance as a result of etanercept treatment either for three, six or 12 months. Out of these, five potential etanercept responsive bi- omarkers were identified. Furthermore, a continuous, significant fall in cfDNA concentration was observed in the serum samples.

Conclusion:Five candidate biomarkers of etanercept treatment response in RA patients were identified. Especially vitamin D-binding protein, pregnancy zone protein, and plasma kallikrein were found to be interest- ing potential biomarkers. Furthermore, lowered cfDNA concentrations may have the ability to be used as a biomarker of RA remission. Future studies are needed to expand the knowledge of the potential biomarkers and their relation to inflammation in RA.
LanguageEnglish
Publication date29 May 2020
Number of pages36
ID: 333204469