P1346 Response to biologic treatment in patients with Crohn’s disease is associated with consistent decreased antibody response to bacterial flagellins
Leibovitzh, H Krongauz, D Schlesinger, Y Hirsch, A Ron, Y Thurm, T Godneva, A Weinberger, A Cohen, N A Segal, E
Leibovitzh, H
Krongauz, D
Schlesinger, Y
Hirsch, A
Ron, Y
Thurm, T
Godneva, A
Weinberger, A
Cohen, N A
Segal, E
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Department
Computational Biology
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Journal article
Date
2025
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English
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Abstract
Background: Patients with Crohn’s disease (CD) exhibit over-representation of antibody-bound peptides derived from bacterial flagellins. Using lon-gitudinal measurements prior to and during treatment, we aimed to assess serum antibody response to bacterial flagellins and related fecal microbial alterations associated with response to treatment. Methods: Thirty-nine patients with active CD (Harvey-Bradshaw Index [HBI]>4 or fecal calprotectin [FCP]>150?g/g) commencing biologic treat-ment (Anti-TNF 56.4%, Ustekinumab 20.5%, Vedolizumab 23.1%) between 1/2018 to 6/2021 in a single tertiary center were included in this study. Serum and stool samples were collected at baseline and during treatment at weeks 14, 22 and 52 (30, 25 and 14 patients with pre-and post-treatment samples, respectively). Remission was defined as HBI? 4 and FCP? 150. Serum samples were analyzed using high-throughput phage-display immunoprecipitation sequencing (PhIP-Seq) to assess antibody response to microbial flagellins. Fecal samples were assessed by DNA shotgun metagenomic sequencing to obtain microbial compositional data. PhIP-Seq data was analyzed using the Wilcox-test on the mean fold change and microbial data was analyzed using a multivariable linear regression mixed effects model. Results: Median age of the cohort was 33.0 [IQR 27.0;46.5] and 19 (48.7%) were females (Table 1). Antibody response against bacterial flagellins was significantly attenuated in patients achieving remission vs. non-remission at all time points (p<0.05) (Figure 1). Remission was associated with change in the abundances of several individual species compared to baseline, including decreased abundance of Ruminococcus_A.sp003011855, Ruminococcus_B gnavus, Klebsiella pneumoniae and Veillonella parvula_A and increased abundance of Roseburia intestinalis, whereas non-remis-sion was associated with increased abundance of Sutterella wadsworthensis (q<0.05 or consistent direction of effect at all different time points). Moreover, most of these taxa belonged to the Lachnospiraceae and Enterobacteriaceae family and Roseburia genera which are the target of anti-flagellin antibodies.Conclusion: Response to biological treatment in patients with CD is associated with consistent decreased antibody response to bacterial flagellins and related fecal microbial alterations compared to non-responders. These findings support the role of anti-bacterial flagellins as a potential marker for treatment response and needs to be further validated in larger cohorts
Citation
H. Leibovitzh et al., “P1346 Response to biologic treatment in patients with Crohn’s disease is associated with consistent decreased antibody response to bacterial flagellins,” J Crohns Colitis, vol. 19, no. Supplement_1, pp. i2424–i2425, Jan. 2025, doi: 10.1093/ECCO-JCC/JJAE190.1520.
Source
Journal of Crohn's and Colitis
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Keywords
tumor necrosis factorsimmunoprecipitationcrohn's diseaseantibody formationbacteriophagesdnaenterobacteriaceaefecesflagellinklebsiella pneumoniaepeptidesveillonellaantibodiesserum specimenlinear regressionustekinumableukocyte l1 antigen complexattenuationstool specimendisease remissionvedolizumabmetagenomic sequencing
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Publisher
Oxford University Press