• Liliana Lykowska-Szuber, Marzena Skrzypczak-Zielinska, Joanna Zuraszek, Michal Walczak, Kamila Stawczyk-Eder, Iwona Krela-Kazmierczak, Michal Michalak, Ryszard Slomski, and Agnieszka Dobrowolska.
• Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznań, Poland. lszuber@wp.pl
• Pol. Arch. Med. Wewn. 2023 Oct 26; 133 (10).

IntroductionCrohn disease (CD) is a chronic inflammatory disease characterized by an uncontrolled immune response of the intestinal mucosal cells to antigens derived from the gut lumen. Specifically, the introduction of anti-tumor necrosis factor (TNF) drugs has changed the approach to the treatment of inflammatory bowel disease, and set new therapeutic goals, such as that of controlling clinical symptoms while simultaneously achieving complete endoscopic and mucosal remission. The mechanisms of action of anti-TNF drugs-and consequently the mechanisms of resistance to anti‑TNF therapy-are unknown.ObjectivesOur study was an attempt to discover whether the potential mechanism of nonresponse may be conditioned by polymorphisms in the genes involved in independent inflammatory or apoptotic pathways.Patients And MethodsThe study included 196 diagnosed and clinically characterized Polish patients with CD treated with anti‑TNF therapy. Variants rs7539036, rs2041747, rs5746053, rs5746054, rs1061624, rs1143634, rs7896789, and rs55790676 of the FCGR3A, IL1R, TNFRSF1B, IL1B, FAS, and ADAM17 genes were genotyped using Sanger sequencing, and analyzed in the context of response to biologic treatment.ResultsWe observed that 33 patients (16.8%) did not respond to the therapy, which was associated with carrying the rs2041747 G allele variant of the ILR1 gene (odds ratio [OR], 3.72; P = 0.009). Moreover, the presence of the FAS rs7896789 homozygous CC genotype correlated with increased susceptibility to the lack of response to the anti‑TNF therapy (OR, 15.22; P = 0.003), whereas TT was identified as a potentially protective genotype.ConclusionsIn patients with CD treated with anti‑TNF drugs, complex pathways with multigene conditioning participate in the mechanism underlying treatment resistance. The genes involved in apoptosis, FAS and ILR1, seem to play an essential role in the lack of response to the treatment, and would be interesting objects of further population and functional research.

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