1. In a small cohort of patients, IL-2 elevation after gluten challenge appears to be the earliest and most sensitive marker of gluten exposure and may play a role in non-invasive diagnostics of celiac disease in the future.
Evidence Level Rating: 2 (Good)
Celiac disease (CeD), an immune-mediated disorder, has an estimated prevalence of approximately 0.7% and is associated with diarrhea, abdominal pain, malabsorption, infertility, and malignancy, among others. Diagnosis of CeD is currently based on a combination of patient-reported symptoms, serological biomarkers, and histological damage seen in mucosal biopsies, all of which have their limitations. This double-blind, randomized controlled trial evaluated the effects of gluten exposure on serum levels of specific biomarkers that may have diagnostic utility. Patients with biopsy-proven CeD in remission were randomized 1:1 to received either 3 g gluten/day or 10 g gluten/day for 14 days. The primary study outcome was villous height to crypt depth ratio (Vh:Cd) at 15 days. 7 patients receiving 3 g gluten and 7 receiving 10 g gluten underwent endoscopic biopsy after gluten challenge. At 15 days, there was a significant change in Vh:Cd in the 10 g cohort (p = 0.0025), while a non-significant change was seen in the 3 g cohort (p = 0.23). All patients had an increased intraepithelial lymphocyte (IEL) count (p = 0.0078). Other dose- and time-dependent changes were noted in the two cohorts. On day 15, there was a 1.5-fold increase of CD8+ T cells in the 3 g cohort and a 1.6-fold increase in the 10 g cohort. In particular, patients in the 10 g cohort were shown to have a 27.1-fold increase in proliferating (Ki67+) memory CD8+ T cells in the epithelium. IL-2 levels also increased in 12 of 14 patients just four hours after gluten challenge (p = 0.0008). After accounting for multiple comparisons, the relationship between IL-2 and IEL count was significant (r = 0.83, p = 0.0004, false discovery rate = 0.018), suggesting its utility in diagnosis. Although the sample size of this study was quite small, it did show how a serum biomarker like IL-2 could feasibly be used in the clinic to assist in the diagnosis of CeD, providing the potential for less invasive investigation.
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