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.