Influence of Adalimumab on the Expression Profile of Genes Associated with the Histaminergic System in the Skin Fibroblasts In Vitro

Wcisło‐Dziadecka, Dominika; Grabarek, Beniamin Oskar; Zmarzły, Nikola; Skubis, Aleksandra; Sikora, Bartosz; Kruszniewska‐Rajs, Celina; Gola, Joanna; Mazurek, Urszula; Kucharz, Eugene J.

doi:10.1155/2018/1582173

Cited by 16 publications

(32 citation statements)

References 55 publications

(46 reference statements)

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“…In the previous paper involving an in vitro model it was shown that changes at the transcriptome level after exposure of skin fibroblasts to adalimumab are possible to be detected after 2 hours of adding the drug to the culture. Moreover, the changes became less noticeable with prolonging the time of cell exposure to the drug [10].…”

Section: Discussionmentioning

confidence: 97%

Drug resistance in anti-TNF therapy of psoriatic arthritis

Wcisło‐Dziadecka¹,

Grabarek²,

Brzeźińska-Wcisło³

et al. 2018

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Introduction. Despite of the molecular targeting anti-TNF therapy, drug resistance may be observed. A method of avoiding this phenomenon, changing treatment early and increasing its effectiveness, the new molecular markers may be used. Objective. To present clinical (PASI, BSA, DAS28, DLQI) and molecular (TNF-α, TNFR1, TNFR2) parameters of loss of efficacy to etanercept in a patient with psoriatic arthritis. Case report. Patient aged 64, initially treated with etanercept then adalimumab because of psoriatic arthritis. During the observation, the loss of response to the anti-TNF drug was observed. During subsequent visits, whole blood was collected from the patient for molecular analysis based on the RTqPCR. Conclusions. Molecular markers such as TNF-α, TNFR1, TNFR2 seem to be useful for early detection of drug resistance and fit into the model of personalised medicine. streszczenie Wprowadzenie. Terapia anty-TNF, mimo molekularnego ukierunkowania działania, wiąże się ze zjawiskiem lekooporności. Sposobem na odpowiednio wczesną zmianę leczenia i zwiększenie jego skuteczności jest zastosowanie nowych markerów molekularnych. Cel pracy. Przedstawienie klinicznych (PASI, BSA, DAS28, DLQI) i molekularnych (TNF-α, TNFR1, TNFR2) parametrów utraty skuteczności leczenia etanerceptem u pacjentki z łuszczycą stawową. Opis przypadku. Pacjentka, lat 64, początkowo leczona etanerceptem, następnie adalimumabem z powodu łuszczycy stawowej. Podczas obserwacji stwierdzono utratę odpowiedzi terapeutycznej na lek anty-TNF. W trakcie kolejnych wizyt pobierano od pacjentki krew pełną do analiz molekularnych z zastosowaniem metody RTqPCR.

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Section: Discussionmentioning

confidence: 97%

Drug resistance in anti-TNF therapy of psoriatic arthritis

Wcisło‐Dziadecka¹,

Grabarek²,

Brzeźińska-Wcisło³

et al. 2018

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“…The identification of novel diagnostic and therapeutic molecular markers constitutes an enormous challenge in molecular biology. Analysis of the transcription changes of genes in molecularly targeted therapy is significant due to the fact that molecular changes precede phenotypic findings (Tables and ; Le Tourneau et al, ; Wcisło – Dziadecka et al, ). As such, an appropriately selected biological marker allows for the detection of a poor response to therapy at an earlier stage.…”

Section: Discussionmentioning

confidence: 99%

The analysis of the therapeutic potential of ustekinumab in psoriasis vulgaris treatment

Wcisło‐Dziadecka

Grabarek

Kruszniewska‐Rajs

et al. 2019

Dermatologic Therapy

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The molecular mechanism of ustekinumab action involves an interruption of signaling pathways activated by IL‐12/23. The aim of this paper was to evaluate the efficacy of the anti‐IL12/23 therapy in seven psoriatic patients by assessing changes in the values of psoriasis area and severity index (PASI), dermatology life quality index (DLQI), body surface area (BSA) indexes, and an analysis of changes in the mRNA expression profile of genes IL12A, IL12B, IL23A during three 40‐week long observation periods. The clinical (PASI, DLQI, BSA indexes) and molecular (RTqPCR for IL12A, IL12B, IL23A) analyses were performed on the day of ustekinumab therapy initiation, 4 weeks post first administration, and every 12 weeks thereafter. The statistically significant differences were observed only during Stage I for values of PASI (p = 0.0134), DLQI (p = 0.01299), BSA (p = 0.0355). During the subsequent stages, we observed lower values of PASI, BSA indexes, which suggests that the lesions are less intensified than at the moment of the therapy commencing. The relationship between the selected genes was observed: IL23A>IL12A>IL12B. In conclusion, the aforementioned clinical and molecular analysis suggests the efficacy of ustekinumab therapy in patients with psoriasis vulgaris can be analyzed with the PASI, BSA, DLQI indexes, and changes in the expression of selected genes. The analysis of IL12A, IL12B, IL23A expression may serve as a valuable supplementation for the therapeutic methods currently used to evaluate the degree of disease progression and treatment efficacy.

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“…Na poziomie molekularnym łuszczyca objawia się zmianą stężeń cytokin, głównie interleukin (IL) -IL-12, (IL) -IL-12, IL-23, IL-17, IL-22 -tumour necrosis factor (TNF), interferon γ (IFN-γ), and transforming growth factor β1-3 (TGF-β1-3) [6,7].…”

Section: Molekularne Podłoże łUszczycy Jej Objawy Oraz Strategie Terunclassified

An analysis of selected factors influencing the efficacy of psoriasis therapy

Grabarek¹,

Krzaczyński²,

Strzałka‐Mrozik³

et al. 2019

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Psoriasis is a chronic disease characterized by a complex immunopathogenesis of recurrent inflammation of the skin. The course and intensity of the disease depend on many genetic, environmental and behavioural factors. The treatment of psoriasis includes a therapy with ultraviolet radiation, methotrexate, cyclosporine A, keratolytic preparations, tar, anthralin, glucocorticoids, calcineurin inhibitors, retinoids, and vitamin D 3 derivatives. A new class of biological drugs (personalized therapy) that was introduced includes cytokine inhibitors, i.e. TNF-etanercept, adalimumab, infliximab, certolizumab pegol, golimumab; IL-12/23ustekinumab; IL-17-secukinumab, ixekizumab, brodalumab. Effective treatment of psoriasis is a challenge. It is an important matter in anticytokine therapy to determine the influence of factors such as age, sex, environmental factors, viral and bacterial infections, an occurrence of comorbidities, individual rate of drug metabolism, and pharmacologic interactions of additionally taken drugs. The influence of many different factors translates into obtaining a heterogeneous adequate response to molecularly targeted treatments. StreSzczenie Łuszczyca jest przewlekłą, nawracającą chorobą zapalną skóry, charakteryzującą się złożoną immunopatogenezą. Przebieg i nasilenie choroby zależą m.in. od czynników genetycznych, środowiskowych i behawioralnych. Łuszczyca istotnie wpływa na komfort i jakość życia pacjenta. Terapia opiera się na różnych strategiach, takich jak leczenie promieniowaniem ultrafioletowym, metotreksatem, cyklosporyną A, preparatami keratolitycznymi, dziegciem, antraliną, glikokortykosteroidami, inhibitorami kalcyneuryny, retinoidami i pochodnymi witaminy D 3. Do nowej klasy leków biologicznych (terapia spersonalizowana) zalicza się inhibitory TNF-etanercept, adalimumab, infliksymab, certolizumab pegol, golimumab; IL-12/23-ustekinumab; IL-17-seku

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Influence of Adalimumab on the Expression Profile of Genes Associated with the Histaminergic System in the Skin Fibroblasts In Vitro

Cited by 16 publications

References 55 publications

Drug resistance in anti-TNF therapy of psoriatic arthritis

Drug resistance in anti-TNF therapy of psoriatic arthritis

The analysis of the therapeutic potential of ustekinumab in psoriasis vulgaris treatment

An analysis of selected factors influencing the efficacy of psoriasis therapy

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