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Phage-display immunoprecipitation sequencing reveals distinct antibody signatures against bacterial flagellins associated with treatment response in Crohn's disease.
Leibovitzh, Haim Krongauz, David Schlesinger, Yishay Cohen, Nathaniel Aviv Hirsch, Ayal Ron, Yulia Thurm, Tamar Godneva, Anastasia Weinberger, Adina Segal, Eran
Leibovitzh, Haim
Krongauz, David
Schlesinger, Yishay
Cohen, Nathaniel Aviv
Hirsch, Ayal
Ron, Yulia
Thurm, Tamar
Godneva, Anastasia
Weinberger, Adina
Segal, Eran
Supervisor
Department
Computational Biology
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Journal article
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http://creativecommons.org/licenses/by/4.0/
Language
English
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Abstract
OBJECTIVES: Enhanced immune response against bacterial flagellins among patients with Crohn's disease (CD) is associated with aggressive disease course. However, its association with response to biologic treatment is unknown. We aimed to assess whether treatment response among patients with CD is associated with antibody reaction to bacterial flagellins and related microbial alterations.
METHODS: Thirty-nine patients with active CD (Harvey-Bradshaw Index [HBI]>4 or fecal calprotectin [FCP]>150μg/g) commencing biologic treatment were included. Serum and stool samples were collected at baseline and during treatment at weeks 14, 22 and 52. Serum samples were analyzed using high-throughput phage-display immunoprecipitation sequencing (PhIP-Seq) and fecal samples by DNA shotgun metagenomic sequencing.
RESULTS: Using PhIP-Seq analysis, only the anti-flagellin antibodies library showed consistently attenuated antibody responses against bacterial flagellins in patients achieving remission (HBI≤4 and FCP≤150) versus non-remission at all time points (p<0.05). Of the 55 anti-flagellin antibodies analyzed, 15 showed consistent >1.5-fold over-representation in non-remission samples, with high conservation of amino-acid sequences and targeting of Clostridiales, Lachnospiraceae, or Roseburia species. Remission was associated with increased abundance of flagellin-target taxa including Roseburia intestinalis and decreased Ruminococcus_B gnavus and pathways involved in cellular oxidative stress, while non-remission showed increased Bacteroides species and pathways involved in 5-aminoimidazole ribonucleotide and semi-essential amino acids biosynthesis (q<0.05).
CONCLUSIONS: PhIP-Seq revealed that biologic treatment response in patients with CD associates with consistently decreased antibody responses against specific bacterial flagellins with conserved sequences. These findings identify potential biomarkers and therapeutic targets for improving treatment outcomes.
Citation
H. Leibovitzh, D. Krongauz, Y. Schlesinger, N.A. Cohen, A. Hirsch, Y. Ron , et al., "Phage-display immunoprecipitation sequencing reveals distinct antibody signatures against bacterial flagellins associated with treatment response in Crohn's disease.," Clinical and Translational Gastroenterology, 2026, https://doi.org/10.14309/ctg.0000000000001030.
Source
Clinical and Translational Gastroenterology
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Keywords
32 Biomedical and Clinical Sciences, 3202 Clinical Sciences
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Publisher
Wolters Kluwer