Altered Antibody Predicts Crohn’s Years Before Diagnosis

TOPLINE:
A unique glycosylation signature on circulating antibodies is detectable in blood up to 6 years before a diagnosis of Crohn’s disease and could serve as a biomarker of future development and a target for preventive strategies.
METHODOLOGY:
Evidence suggests that a preclinical period characterized by immunological changes precedes both symptom onset and diagnosis of Crohn’s disease.
Researchers studied the transition from preclinical to clinical Crohn’s disease, focusing on the intestinal inflammation specifically characteristic of Crohn’s disease.
They analyzed thousands of serum samples from the preclinical PREDICTS cohort, which includes longitudinal samples many years before an inflammatory bowel disease (IBD) diagnosis.
They compared serum samples from individuals with Crohn’s disease, individuals with ulcerative colitis, and controls at four timepoints: 2, 4, and 6 years before diagnosis, and at the time of diagnosis.
TAKEAWAY:
Researchers identified a serum glycome signature on circulating antibodies (immunoglobulin G [IgG]) that is detectable up to 6 years before a diagnosis of Crohn’s disease.
The IgG glycome signature is specific for Crohn’s disease and was not seen in ulcerative colitis or control samples.
Researchers also showed that the altered glycome signature, detected preclinically, correlated with the presence of an anti-Saccharomyces cerevisiae antibody (ASCA).
The preclinical ASCA IgG glycoform was able to activate innate immune cells toward a proinflammatory phenotype that increased susceptibility to intestinal inflammation in mice.
Researchers concluded that ASCA IgGs may serve as a classical biomarker for IBD and also play a key role in the inceptive stages of initiation of a proinflammatory response in the gut, potentially triggering a more aggressive inflammatory response.
IN PRACTICE:
“This study not only highlights a new preclinical biomarker of Crohn’s disease development associated with Crohn’s disease pathogenesis but also helps define a new target for future preventive strategies for IBD and other immune-mediated diseases,” the authors wrote.
SOURCE:
The study, led by Joana Gaifem, University of Porto, Porto, Portugal, was published online in Nature Immunology.
LIMITATIONS:
This is a preclinical study that analyzed serum samples from individuals with Crohn’s disease, ulcerative colitis, and controls. A clinical trial in patients with Crohn’s disease is planned for 2025 (according to a press release).
DISCLOSURES:
The details of funding for specific coauthors are included in the study. One author is the founder and owner of Genos, Ltd., a private research organization that specializes in high-throughput glycomic analysis, and has several patents in this field. Two other authors are employees of Genos, Ltd. The other authors declared no competing interests.
 
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