# Immune responses to ex vivo gluten challenge in children with celiac disease

> **NIH NIH R03** · BOSTON CHILDREN'S HOSPITAL · 2024 · $132,750

## Abstract

Project Summary/Abstract
Celiac disease is a chronic immune disorder driven by gluten that typically develops in childhood. Over 1% of
the world population is affected, many of whom are undiagnosed. Many more have an uncertain diagnosis
because current diagnostic tests are not reliable in individuals following a gluten-free diet. Therefore, there is a
strong need for better diagnostic methods that reflect the underlying causes of celiac disease and overcome the
limitations of existing tests. Previous studies have shown that an increase in a cytokine called interleukin 2 (IL-
2) is the earliest and most sensitive marker of acute gluten ingestion in adults with celiac disease who are on a
gluten-free diet. This method is not practical for diagnosis because patients who are on a gluten-free diet do not
want to suffer symptoms of gluten ingestion and it is impractical for patients who are eating gluten to go on a
gluten-free diet treatment just to confirm the diagnosis. An alternative to challenging patients with gluten is to
challenge the immune cells in blood with gluten. In over 300 adults with celiac disease on a gluten-free diet, an
ex vivo whole blood gluten challenge assay in which IL-2 is measured after blood has been incubated with gluten
had near perfect specificity and high sensitivity for adults with celiac disease treated with a gluten-free diet. There
is a need to conduct studies in children because celiac disease typically develops in this age group. As well,
there may be age-related differences in immune responses. Therefore, the main goal of this research grant is to
further investigate the immune response to gluten in children with celiac disease using the ex vivo gluten
challenge whole blood assay. A cohort of 80 children with celiac disease (40 treated and 40 untreated) will be
recruited. In Aim 1, the sensitivity of IL-2 rise in the ex vivo gluten challenge whole blood assay will be determined
in the overall cohort. In a pre-planned secondary analysis, sensitivity in treated and untreated celiac disease will
be compared. In Aim 2, an immune response signature of ex vivo gluten challenge will be determined using a
panel of cytokines known to be elevated following oral gluten challenge (CCL20, CXCL9, IFN-γ, IL-2, IL-8, IL-10,
IL-17A, IL-22, IP-10, and TNF-α). The sensitivity of each cytokine for detecting celiac disease will be determined
as well as whether using a combination of cytokines improves the accuracy of the test. This novel study will
determine whether IL-2 release in ex vivo gluten challenge whole blood assay is a sensitive marker of celiac
disease in children. Critically, it will also be determined whether ex vivo gluten challenge evokes an immune
response in children with untreated celiac disease. Results of this study will guide protocol development for a
multi-center clinical trial to determine the diagnostic accuracy of cytokine release following gluten challenge for
diagnosis of celiac disease. Results of this tri...

## Key facts

- **NIH application ID:** 10871122
- **Project number:** 1R03DK139281-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Jocelyn Anne Silvester
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $132,750
- **Award type:** 1
- **Project period:** 2024-05-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10871122

## Citation

> US National Institutes of Health, RePORTER application 10871122, Immune responses to ex vivo gluten challenge in children with celiac disease (1R03DK139281-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10871122. Licensed CC0.

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