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Research & Innovation January 30, 2025

Stream CrohnsResearchers identified that the dominant B cell epitope of Lachnospiraceae flagellins and the utilization of the flagellin peptide cytometric bead array can potentially advance the diagnosis and prognosis of Crohn’s disease.Crohn’s disease, a type of inflammatory bowel disease, is characterized as relapsing and remitting chronic inflammation that primarily affects the gastrointestinal tract. Unlike ulcerative colitis, which is limited to the colon and rectum, Crohn’s disease can affect any part of the GI tract.

In a study published in and featured on the cover of Gastroenterology, the official journal of the American Gastroenterological Association, researchers at the University of Alabama at Birmingham identified the dominant region shared by hundreds to thousands of different flagellins that drives the elevated serum IgG response in Crohn’s patients. Researchers showed that reactivity to this dominant region at Crohn’s diagnosis is positively associated with the future development of disease complications. This was done through utilizing a prospective cohort study.

“Surprisingly, most of the geographically distinct healthy infants at the age of 1 also exhibit potent serum IgG response to the same region of flagellins, suggesting failure of a homeostatic response to the gut microbiota in Crohn’s patients may have started in infancy,” said Qing Zhao, Ph.D., assistant professor in the UAB School of Medicine’s Division of Gastroenterology and Hepatology and lead author.

Immunoglobulin G, or IgG, is the most abundant antibody in the human blood, accounting for approximately 70-75 percent of total serum immunoglobulins. Serum IgG antibodies are often elevated in Crohn’s disease and may target normal gut bacteria, reflecting a loss of immune tolerance. This signifies that these antibodies may serve as biomarkers for disease diagnosis and prognosis.

“In Crohn’s disease, the immune system exhibits heightened reactivity to flagellins from gut commensal bacteria, such as those from the Lachnospiraceae family,” Zhao said.

Lachnospiraceae is a diverse family of normal gut residential bacteria found in humans and other animals. This bacterium is considered beneficial because of its ability to ferment dietary fibers into short-chain fatty acids, which is critical for the maintenance of healthy gut epithelial cells and regulatory CD4 T cells. However, in people with Crohn’s, flagellins expressed by Lachnospiraceae drive potent immune responses in said patients.

Qing ZhaoQing Zhao, Ph.D.,
Photography: Lexi Coon
Utilizing a cytometric bead array, a flow cytometry-based technology designed for the simultaneous quantification of multiple analytes within a single sample with high sensitivity, researchers utilized beads with different fluorescent intensities. Each bead was pre-coated with one of eight consensus peptides representing the conserved regions of Lachnospiraceae flagellins. This allowed them to detect and measure serum IgG reactivity to these eight peptides simultaneously.

Research showed that healthy infants mount a robust IgG response to the same epitope.

“Anti-flagellin reactivity has been discovered and used in the clinic for Crohn’s diagnosis for more than two decades,” Zhao said. “However, it was unknown which part of the flagellin protein was targeted by serum IgG antibodies.”

The identification of the dominant B cell epitope of Lachnospiraceae flagellins and the utilization of the flagellin peptide cytometric bead array can potentially advance the diagnosis and prognosis of Crohn’s disease by offering a simplified yet robust and standardized assay to measure the serum IgG reactivity in patients.

“This technique may also help identify Crohn’s patients who would benefit from early therapy,” Zhao said. “Additionally, the findings in this study offer a biological target for the development of antigen-directed immunotherapies of Crohn’s disease.”

This study was led by Zhao and UAB professor Charles O. Elson, M.D., in collaboration with colleagues at UAB, as well as researchers from the University of Nebraska Medical Center, the University of Cincinnati, Ohio; Emory University, Georgia; the University of Colorado Denver; and Linköping University, Sweden.


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