Ellen G. van Lochem

Background: To determine the applicability and sensitivity of a urine self-test to detect gluten-immunogenic-peptides (GIP) in daily-life for patients with coeliac disease and correlate the test results with reported symptoms. Methods: We performed a prospective double-blinded placebo-controlled study, including adults with coeliac disease adhering to a strictly gluten-free diet. Patients were administered gluten in test-cycles of ascending doses of 50, 100, 200, and 500 mg alternated with placebo. Urine portions from 2, 5–17 h after the ingestion were collected and analyzed for GIP using the iVYCHECK-GIP-Urine rapid lateral flow test. Patients completed a diary mapping symptoms (nausea, bloating, diarrhea, abdominal pain, and lower level of energy). Results: We enrolled 15 patients and 7 received all 4 cycles with increasing gluten dosing. GIP was detected from urine in 47% of the patients receiving 50 mg gluten and in 86% with 500 mg gluten. We detected GIP in 20–50% of urine samples after placebo. There was no correlation between symptoms, gluten administration and/or GIP in urine. Conclusions: Gluten intake, even with a dose as low as 50 mg, leads to detectable urinary GIP concentrations. There is no correlation of coeliac disease ascribed symptoms with detection of urinary GIP.

PNAd and MAdCAM-1 addressins on venules are of importance in T-cell homing and potential therapeutic targets in ulcerative colitis (UC). Normally, PNAd⁺ high endothelial venules (HEVs) are only present in lymphoid organs, whereas small numbers of MAdCAM-1⁺ venules can be seen in non-lymphoid tissue. We aimed to study their presence in the intestinal mucosa of UC patients at diagnosis and during follow-up, and their correlation with disease activity. Colonic biopsy specimens of 378 UC patients were analyzed by immunohistochemistry for CD3, CD20, ERG, MECA-79 (PNAd) and MECA-376 (MAdCAM-1) and compared to healthy controls (HC). The proportion of PNAd⁺HEVs in UC at diagnosis was 4.9% (IQR 2.0%–8.3%), while none were detected in HC. During follow-up, PNAd⁺HEVs completely disappeared in remission (n = 93), whereas the proportion in active disease was similar to baseline (n = 285, p = 0.39). The proportion of MAdCAM-1⁺venules in UC at baseline was 5.8% (IQR 2.6–10.0). During follow-up, the proportion in remission was comparable to diagnosis, but upregulated (7.5% (IQR 4.4–10.9), p = 0.001) in active disease. In conclusion, PNAd⁺HEVs appear in UC during active inflammation which could thus serve as a marker for disease activity, whereas MAdCAM-1⁺venules remain present after inflammation is resolved and increase after subsequent flares, reflecting chronicity and potentially serving as a therapeutic target.