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Effect of Anti-TNF Therapy on Mucosal Apoptosis Genes Expression in Crohn's Disease

Crohn's disease (CD) is a chronic immune-mediated disorder for which there is not a fully effective treatment. Moreover, biological therapy with anti-tumor necrosis factor-α (anti-TNF-α) monoclonal antibodies leads to an effective response in only 60–70% of patients. Our previous data suggested...

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Autores principales: Lykowska-Szuber, Liliana, Walczak, Michal, Skrzypczak-Zielinska, Marzena, Suszynska-Zajczyk, Joanna, Stawczyk-Eder, Kamila, Waszak, Katarzyna, Eder, Piotr, Wozniak, Anna, Krela-Kazmierczak, Iwona, Slomski, Ryszard, Dobrowolska, Agnieszka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985326/
https://www.ncbi.nlm.nih.gov/pubmed/33767696
http://dx.doi.org/10.3389/fimmu.2021.615539
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author Lykowska-Szuber, Liliana
Walczak, Michal
Skrzypczak-Zielinska, Marzena
Suszynska-Zajczyk, Joanna
Stawczyk-Eder, Kamila
Waszak, Katarzyna
Eder, Piotr
Wozniak, Anna
Krela-Kazmierczak, Iwona
Slomski, Ryszard
Dobrowolska, Agnieszka
author_facet Lykowska-Szuber, Liliana
Walczak, Michal
Skrzypczak-Zielinska, Marzena
Suszynska-Zajczyk, Joanna
Stawczyk-Eder, Kamila
Waszak, Katarzyna
Eder, Piotr
Wozniak, Anna
Krela-Kazmierczak, Iwona
Slomski, Ryszard
Dobrowolska, Agnieszka
author_sort Lykowska-Szuber, Liliana
collection PubMed
description Crohn's disease (CD) is a chronic immune-mediated disorder for which there is not a fully effective treatment. Moreover, biological therapy with anti-tumor necrosis factor-α (anti-TNF-α) monoclonal antibodies leads to an effective response in only 60–70% of patients. Our previous data suggested that specific loci polymorphism of the TNFRSF1B, FCGR3A, IL1R, IL1B, and FAS genes could be a predictor of the primary non-response to anti-TNF therapy in CD patients. In this work, we propose to explain this hypothesis by functional analysis in colon biopsies and in a cell culture model. Using the RT-qPCR analysis, we estimated the FCGR3A, IL1R, TNFRSF1B, IL1B, FAS, and ADAM17 genes mRNA level in colon biopsies material from inflamed and non-inflamed tissue from 21 CD patients (14 responders and 7 non-responders to anti-TNF therapy) and 6 controls, as well as in vitro in a peripheral blood mononuclear cells (PBMCs) from 14 CD patients (seven responders and seven non-responders to anti-TNF therapy) and eight controls cultured for 72 h with 10 μg/ml of anti-TNF antibody. Our findings demonstrated a significant down-regulation of TNFRSF1B gene expression in non-responders both in inflamed and in non-inflamed colon tissue, while the expression of the FCGR3A and IL1B genes was significantly up-regulated in non-responders in the inflamed colon region. In vitro research results indicate that the anti-TNF drug induced a significant decrease in TNFRSF1B, FCGR3A, and FAS gene expression in non-responders. These results show that altered TNFRSF1B, FCGR3A, and IL1B genes expression can be a predictor of the primary non-response to anti-TNF therapy in CD patients.
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spelling pubmed-79853262021-03-24 Effect of Anti-TNF Therapy on Mucosal Apoptosis Genes Expression in Crohn's Disease Lykowska-Szuber, Liliana Walczak, Michal Skrzypczak-Zielinska, Marzena Suszynska-Zajczyk, Joanna Stawczyk-Eder, Kamila Waszak, Katarzyna Eder, Piotr Wozniak, Anna Krela-Kazmierczak, Iwona Slomski, Ryszard Dobrowolska, Agnieszka Front Immunol Immunology Crohn's disease (CD) is a chronic immune-mediated disorder for which there is not a fully effective treatment. Moreover, biological therapy with anti-tumor necrosis factor-α (anti-TNF-α) monoclonal antibodies leads to an effective response in only 60–70% of patients. Our previous data suggested that specific loci polymorphism of the TNFRSF1B, FCGR3A, IL1R, IL1B, and FAS genes could be a predictor of the primary non-response to anti-TNF therapy in CD patients. In this work, we propose to explain this hypothesis by functional analysis in colon biopsies and in a cell culture model. Using the RT-qPCR analysis, we estimated the FCGR3A, IL1R, TNFRSF1B, IL1B, FAS, and ADAM17 genes mRNA level in colon biopsies material from inflamed and non-inflamed tissue from 21 CD patients (14 responders and 7 non-responders to anti-TNF therapy) and 6 controls, as well as in vitro in a peripheral blood mononuclear cells (PBMCs) from 14 CD patients (seven responders and seven non-responders to anti-TNF therapy) and eight controls cultured for 72 h with 10 μg/ml of anti-TNF antibody. Our findings demonstrated a significant down-regulation of TNFRSF1B gene expression in non-responders both in inflamed and in non-inflamed colon tissue, while the expression of the FCGR3A and IL1B genes was significantly up-regulated in non-responders in the inflamed colon region. In vitro research results indicate that the anti-TNF drug induced a significant decrease in TNFRSF1B, FCGR3A, and FAS gene expression in non-responders. These results show that altered TNFRSF1B, FCGR3A, and IL1B genes expression can be a predictor of the primary non-response to anti-TNF therapy in CD patients. Frontiers Media S.A. 2021-03-09 /pmc/articles/PMC7985326/ /pubmed/33767696 http://dx.doi.org/10.3389/fimmu.2021.615539 Text en Copyright © 2021 Lykowska-Szuber, Walczak, Skrzypczak-Zielinska, Suszynska-Zajczyk, Stawczyk-Eder, Waszak, Eder, Wozniak, Krela-Kazmierczak, Slomski and Dobrowolska. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lykowska-Szuber, Liliana
Walczak, Michal
Skrzypczak-Zielinska, Marzena
Suszynska-Zajczyk, Joanna
Stawczyk-Eder, Kamila
Waszak, Katarzyna
Eder, Piotr
Wozniak, Anna
Krela-Kazmierczak, Iwona
Slomski, Ryszard
Dobrowolska, Agnieszka
Effect of Anti-TNF Therapy on Mucosal Apoptosis Genes Expression in Crohn's Disease
title Effect of Anti-TNF Therapy on Mucosal Apoptosis Genes Expression in Crohn's Disease
title_full Effect of Anti-TNF Therapy on Mucosal Apoptosis Genes Expression in Crohn's Disease
title_fullStr Effect of Anti-TNF Therapy on Mucosal Apoptosis Genes Expression in Crohn's Disease
title_full_unstemmed Effect of Anti-TNF Therapy on Mucosal Apoptosis Genes Expression in Crohn's Disease
title_short Effect of Anti-TNF Therapy on Mucosal Apoptosis Genes Expression in Crohn's Disease
title_sort effect of anti-tnf therapy on mucosal apoptosis genes expression in crohn's disease
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985326/
https://www.ncbi.nlm.nih.gov/pubmed/33767696
http://dx.doi.org/10.3389/fimmu.2021.615539
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