Acute gluten-induced inflammatory response highlights CCL20 as a potential biomarker for celiac disease

Background: Diagnosis of celiac disease (CD) remains challenging in individuals already on a gluten-free diet (GFD). Although several alternative methods have been proposed, they have limitations. Identifying inflammation-related proteins that rapidly respond to gluten exposure in blood may offer diagnostic alternatives. We aimed to characterize the inflammatory protein response to gluten in patients with CD on a GFD, and to assess the diagnostic potential of candidate biomarkers and their association with clinical symptoms. Methods: Seventeen patients with CD and 15 non-CD individuals on a GFD (≥ 1 month) consumed 10 g of gluten. Serum, plasma and clinical symptoms were collected at baseline and 4 h post-gluten ingestion to assess changes in 92 inflammation-related proteins. CCL20 levels were also measured by ELISA in plasma from 13 patients with CD and 11 non-CD individuals from the initial cohort, and in an additional group of 28 individuals evaluated for suspected CD, three of whom received a final diagnosis of CD. In 15 patients with CD, the results were compared to those of other diagnostic approaches. Results: Twelve proteins showed significantly different fold changes following gluten challenge between CD and non-CD groups. Six showed an AUC ≥80%, and CCL20 achieved 81.3-85.7% sensitivity and 88.9-92.7% specificity for CD diagnosis. CCL20 level increases post-gluten challenge were higher in patients with vomiting but were also observed in those with absent or mild symptoms. Conclusion: Gluten reintroduction triggers alterations in the inflammation-related protein profile of patients with CD. CCL20 emerges as a promising diagnostic candidate, its increase in plasma or serum, with low dependence on symptom presentation, may complement existing diagnostic approaches.