TOPLINE

Adults with untreated celiac disease (CeD) had higher levels of inflammatory proteins in their blood than control individuals without CeD, with levels tracking both celiac antibody titers and the severity of intestinal damage. The levels of these proteins generally decreased after a year on a gluten-free diet, but several proteins remained elevated, hinting that some patients may carry quiet, low-grade inflammation even a year into treatment.

METHODOLOGY

• Although CeD is driven by a gluten-triggered immune response in the small intestine, whether these gut immune processes are reflected systemically in the bloodstream remains unclear.
• Researchers conducted a case-control study to investigate the presence of inflammatory proteins in the serum of adults with CeD and the association of these proteins with CeD antibodies and the severity of intestinal injury.
• They analyzed serum samples from 161 adults (mean age, 37.4 years; 64% women) with untreated biopsy-confirmed CeD and compared them with serum samples from 40 control individuals (mean age, 36.8 years; 67.5% women) with biopsy-proven absence of CeD, negative serology, and normal duodenal histology. A subset of 63 adults (mean age, 36.6 years; 65.1% women) provided follow-up serum after a median of 12.4 months on a gluten-free diet.
• Using a targeted proteomics platform, the levels of 92 inflammatory proteins were measured in serum samples collected at the time of diagnostic gastroduodenoscopy; the primary outcome was serum normalized protein expression, with a 1-unit increase corresponding to a doubling of relative protein levels.
• Gut damage severity was graded on biopsy using the established Marsh scale.

TAKEAWAY

• Of the 92 inflammatory proteins measured, 24 were elevated in adults with untreated CeD compared with control individuals; 23 remained significantly associated with CeD after adjustment for age, sex, and repeated measures.
• Inflammatory protein levels generally fell in adults on a gluten-free diet, but the levels of nine proteins remained significantly elevated. For most proteins, levels were typically highest in untreated CeD, lowest in control individuals, and intermediate in treated CeD, suggesting possible persistent low-grade inflammation despite dietary treatment.
• Several inflammatory proteins were associated with higher CeD antibody levels, linking blood-based inflammatory activity with established markers of disease burden.
• Five inflammatory proteins were associated with the severity of gut damage; three of them distinguished healthy, near-normal mucosa from the most severe lesions, whereas the other two proteins distinguished between different degrees of severe damage; patients with damage confined to the duodenal bulb had significantly lower levels of one of those inflammatory proteins than other patients with CeD.

IN PRACTICE

"The increase of these inflammatory markers may play a role in systemic manifestations of CeD. The serum markers may improve diagnostic accuracy in a non-biopsy setting and offer possibilities to monitor sustained inflammation and failed mucosal healing of patients on a gluten-free diet," the authors wrote.

SOURCE

The study was led by Jostein H. Ibsen, University of Oslo, Oslo, Norway. It was published online as a research letter in Gastroenterology.

LIMITATIONS

The study used an exploratory design, and no formal power calculation was performed.

DISCLOSURES

The study was funded by South-East Health Authorities and was a part of a PhD project and the translational and Clinical Trial Centre for Coeliac Disease. It also received financial support from Oslo University Hospital Fund. Some authors disclosed being a consultant and/or receiving speaker honoraria from multiple companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.