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Določanje nivoja anti-TNF bioloških zdravil in nastajanja protiteles proti zdravilu med zdravljenjem kronične vnetne črevesne bolezni
Pušavec, Saša (Author), Ihan, Alojz (Mentor) More about this mentor... This link opens in a new window, Drobne, David (Co-mentor)

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Abstract
Med zdravljenjem kronične vnetne črevesne bolezni z anti-TNF biološkimi zdravili je pomembno, da spremljamo nivoje zdravila in nivoje protiteles proti zdravilu, ki se pojavijo zaradi imunogenosti zdravila, saj lahko s tem optimiziramo zdravljenje bolnika. V raziskavi smo primerjali dva komercialno dostopna testa za določanje najnižje serumske koncentracije zdravila infliksimab (angl. trough level of infliximab – TL IFX) – test Lisa-Tracker Duo Infliximab (Lisa-Tracker) in test apDia Infliximab ELISA (apDia) ter rezultate primerjali z rezultati komercialno nedostopnega testa, razvitega na Univerzi v Leuvnu (UHL). Pearsonovi koeficienti korelacije med testi so znašali R = 0,92 (UHL in apDia), R = 0,91 (apDia in Lisa-Tracker) ter R = 0,89 (UHL in Lisa-Tracker). Dokazali smo povezanost TL IFX s koncentracijo C-reaktivnega proteina pri vseh treh testih ter povezanost TL IFX z endoskopsko določeno aktivnostjo bolezni pri testih UHL in Lisa-Tracker. Dokazali smo, da so zaznavni TL IFX dober napovedovalec, da bo bolnik ostal na terapiji z IFX. Izmerili smo tudi protitelesa proti IFX (angl. antibodies to infliximab – ATI) in sicer s komercialno dostopnim testom Lisa-Tracker, rezultate pa kvalitativno primerjali z rezultati komercialno nedostopnega testa za določanje ATI – UHL. Pri obeh testih je odsotnost ATI dober napovedovalec, da bo bolnik ostal na terapiji z IFX. Odsotnost ATI (določena z UHL) pomeni večjo verjetnost, da bodo zaznavni TL IFX s časom ostali zaznavni, prisotnost ATI pa je povezana z manjšo verjetnostjo, da bodo TL IFX postali visoki.

Language:Slovenian
Keywords:črevesne bolezni, kronična vnetna črevesna bolezen, zdravljenje, biološka zdravila, anti-TNF, infliksimab, imunokemijske metode, ELISA
Work type:Master's thesis/paper (mb22)
Tipology:2.09 - Master's Thesis
Organization:BF - Biotechnical Faculty
Year:2017
Publisher:[S. Pušavec]
UDC:615.32:616.34
COBISS.SI-ID:4843128 Link is opened in a new window
Views:882
Downloads:562
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Secondary language

Language:English
Title:Determination of anti-TNF biologic drugs and anti-drug antibodies in inflammatory bowel disease
Abstract:
Monitoring trough levels of the drug and antibodies to the drug is important when patients with inflammatory bowel disease are treated with anti-TNF biological drugs, because it can help to guide therapeutic decisions. In our research we compared two commercial assays for measuring trough level of infliximab (TL IFX) – test Lisa-Tracker Duo Infliximab (Lisa-Tracker) and test apDia Infliximab ELISA (apDia). We compared our results to in-house developed ELISA test from University of Leuven (UHL). Linear correlations (Pearson R) between tests were R = 0,92 (UHL and apDia), R = 0,91 (apDia and Lisa-Tracker) and R = 0,89 (UHL and Lisa-Tracker). Our results indicate that TL IFX, meassured with three different assays correlate with concentration of C-reactive protein. Higher TL IFX, measured with UHL and Lisa-Tracker also correlate with endoscopic remission of disease. We showed that detectable TL IFX lead to continuation of the treatment with IFX. In our research we measured antibodies to infliximab (ATI) with commercial test Lisa-Tracker and compared our results with in-house developed ELISA test – UHL. Because of a lack of standardization among assays for ATI determination, we can only compare results qualitative. We found out that the absence of ATI, measured with both assays leads to continuation of treatment with IFX. When determinating predictors for high TL IFX in the future, the absence of ATI (determinated with UHL) was found out to be a good predictor for detectable TL IFX in the future.

Keywords:bowel diseases, inflammatory bowel disease, treatment, biologic drugs, anti-TNF, infliximab, immunochemical methods, ELISA

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