IDDF2024-ABS-0451 Comparison of the serum and gut tissue cytokine profile in crohn’s disease patients with ATG16L1 gene polymorphism (rs2241880)

<h3>Background</h3> The pathogenesis of Crohn’s disease (CD) is considered from a multifactorial perspective with an undeniable contribution of the genetic component. The various ATG16L1 gene variants are strongly associated with susceptibility to Crohn’s disease in different populations. It is also known that the cytokine profile is considered as a complex signature of the inflammatory process both locally and in an organism. The aim of the study was to assess the local and systemic cytokine profile in L1 ileal CD patients in clinical remission. <h3>Methods</h3> Serum samples, ileal and rectal tissue biopsies were obtained from CD patients (n=11) aged 19 - 66 y.o. All patients had previously documented L1 ileal CD and clinical remission. DNA samples of CD patients for exome sequencing were isolated from the whole blood. Identified rs2241880 had a coverage depth of more than 30x (MGI, FCL PE100, 6 GB per sample). The risk allele of ATG16L1 (rs2241880) was found in 7 of 11 L1 ileal CD patients. The local (ileal and rectal biopsies) and systemic (serum) cytokine profile were analyzed by bio-plex technology (pro-human cytokine 27-plex assay #M500KCAF0Y) in accordance with the manufacturer’s instructions. <h3>Results</h3> Integral local and systemic cytokine profile analysis showed significant variability in cytokine profile in patients according to the allelic variant of ATG16L1 (rs2241880). The most significant differences in CD patients with risk allele of ATG16L1 (rs2241880) were found in IL-8, IL-9, IL-17, MCP-1, MIP-1a, MIP-1b, and RANTES profiles in gut tissue and serum compared to patients without risk allele of ATG16L1. The most significant variability was assessed in IL-9: 171.7±10,01 pg/ml (serum) vs 1251.0±66,26 pg/mg (ileal) vs 422.0±140.62 pg/mg (rectal), IL-17: 60.0±1.57 pg/ml (serum) vs 113.5±29.5 pg/mg (ileal) vs 108,25+24,75 pg/mg (rectal), RANTES: 41.98+8.55 pg/ml (serum) vs 204.25+130.5 pg/ml (ileal) vs 186.5+75.5 pg/mg (rectal). <h3>Conclusions</h3> SNP analysis in combination with an immunological portrait are additional methods for precision medicine in Crohn’s disease even in the state of clinical remission.