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 

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.615539

DOI=10.3389/fimmu.2021.615539

ISSN=1664-3224

ABSTRACT=<p>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 <italic>loci</italic> polymorphism of the <italic>TNFRSF1B, FCGR3A, IL1R, IL1B</italic>, and <italic>FAS</italic> 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 <italic>FCGR3A, IL1R, TNFRSF1B, IL1B, FAS</italic>, and <italic>ADAM17</italic> 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 <italic>in vitro</italic> 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 <italic>TNFRSF1B</italic> gene expression in non-responders both in inflamed and in non-inflamed colon tissue, while the expression of the <italic>FCGR3A</italic> and <italic>IL1B</italic> genes was significantly up-regulated in non-responders in the inflamed colon region. <italic>In vitro</italic> research results indicate that the anti-TNF drug induced a significant decrease in <italic>TNFRSF1B, FCGR3A</italic>, and <italic>FAS</italic> gene expression in non-responders. These results show that altered <italic>TNFRSF1B, FCGR3A</italic>, and <italic>IL1B</italic> genes expression can be a predictor of the primary non-response to anti-TNF therapy in CD patients.</p>