Identification of Etanercept Responsive Biomarkers in Rheumatoid Arthritis
Translated title
Identikfikation af Etanercept-Responsive Biomarkører i Reumatoid Artritis
Author
Andersen, Jacob Skallerup
Term
4. term
Publication year
2020
Submitted on
2020-05-29
Pages
36
Abstract
Reumatoid artrit (RA), også kaldet leddegigt, er en kronisk betændelsessygdom i leddene. Uden effektiv behandling kan den ødelægge led og knogler og øge risikoen for hjerte- og lungesygdom. Biologiske sygdomsmodificerende lægemidler (bDMARDs) har forbedret behandlingen af RA. Etanercept er et af disse lægemidler: et genetisk fremstillet fusionsprotein, der fungerer som en lokke- (decoy) receptor for TNF‑alfa, et signalstof der driver inflammation. Derved dæmpes TNF‑alfa‑signalering. Alligevel opnår 30–40% af patienterne ikke remission eller lav sygdomsaktivitet med anti‑TNF‑alfa-behandling. Formålet med dette studie var at undersøge effekten af langvarig etanerceptbehandling ved RA og at finde blodbaserede biomarkører, som kan bruges til at overvåge behandlingsrespons. Serum fra 12 RA‑patienter blev indsamlet før opstart og efter 3, 6 og 12 måneder på etanercept. Prøverne blev analyseret proteomisk med massespektrometri (LC‑MS/MS), og niveauet af cirkulerende frit DNA (cfDNA)—små DNA-fragmenter i blodet—blev målt. I alt ændrede 79 proteiner sig signifikant efter 3, 6 eller 12 måneders behandling. Blandt disse blev fem mulige biomarkører for etanerceptrespons identificeret. Der sås også et vedvarende, signifikant fald i cfDNA i serum over tid. Konklusionen er, at fem kandidater—særligt vitamin D‑bindende protein, pregnancy zone protein og plasma kallikrein—fremstår som interessante biomarkører for behandlingsrespons. Desuden kan faldende cfDNA-niveauer muligvis bruges som en biomarkør for remission ved RA. Fremtidige studier er nødvendige for at bekræfte fundene og afklare deres relation til inflammation ved RA.
Rheumatoid arthritis (RA) is a chronic inflammation of the joints. Without effective treatment, it can damage joints and bones and increase the risk of heart and lung disease. Biologic disease‑modifying drugs (bDMARDs) have improved RA care. Etanercept is one such drug: a genetically engineered fusion protein that acts as a decoy receptor for TNF‑alpha, a signaling molecule that drives inflammation. This reduces TNF‑alpha signaling. Still, 30–40% of patients do not reach remission or low disease activity with anti‑TNF‑alpha therapy. This study aimed to assess the long‑term effects of etanercept in RA and to identify blood‑based biomarkers to monitor treatment response. Serum from 12 RA patients was collected before treatment and after 3, 6, and 12 months on etanercept. Samples were analyzed proteomically by mass spectrometry (LC‑MS/MS), and levels of circulating cell‑free DNA (cfDNA)—small DNA fragments in the blood—were measured. In total, 79 proteins changed significantly after 3, 6, or 12 months of treatment. Among these, five potential biomarkers of response to etanercept were identified. A continuous, significant decline in serum cfDNA was also observed over time. In conclusion, five candidates—especially vitamin D‑binding protein, pregnancy zone protein, and plasma kallikrein—appear to be promising biomarkers for treatment response. In addition, decreasing cfDNA levels may serve as a biomarker of RA remission. Further studies are needed to confirm these findings and clarify their relationship to RA‑related inflammation.
[This abstract was generated with the help of AI]
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