Safety and efficacy of AMG 714 in adults with coeliac disease exposed to gluten challenge: a phase 2a, randomised, double-blind, placebo-controlled study

Baseline quantitative histology in therapeutics trials reveals villus atrophy in most patients with coeliac disease who appear well controlled on gluten‐free diet

“…Quantitative histology provides accurate assessment of duodenal mucosal injury in coeliac disease by using highly reproducible measurements of villous height, crypt depth and intraepithelial lymphocyte density in well‐oriented distal duodenal biopsies . With implementation of rigorous standard operating procedures, quantitative duodenal histology outperforms conventional qualitative histology using grouped classifications such as Marsh score, and is emerging as a preferred measure of efficacy in therapeutics trials for coeliac disease . Perhaps surprisingly, quantitative histology has not yet, to our knowledge, been used to evaluate disease activity/duodenal injury in patients with coeliac disease who appear clinically ‘well controlled’ and are in serological remission.…”

Genome-Wide Transcriptomic Analysis of Intestinal Mucosa in Celiac Disease Patients on a Gluten-Free Diet and Postgluten Challenge

“… 13 , 21 , 24 , 62 These methods were also adopted in recent clinical drug and vaccine trials. 22 , 23 , 39 In the present study, we show that the expression of a selected subset of protein-coding genes correlates extremely well with the extent of morphological damage and inflammation in control patients and celiac disease patients on a GFD before and after the gluten challenge (presented as heatmaps in the order of VH:CrD and IEL density in Figure 10 ). It should be noted that the RNA was extracted from separate cuttings but from the same paraffin-embedded biopsy blocks that had been used for morphometry measurements, thus avoiding the patchy lesion pitfalls observed between biopsies in short gluten challenges using low and moderate amounts of gluten.…”

“…Fifteen adult HLA-DQ2 positive patients having a biopsy-proven celiac disease diagnosis were enrolled for this study. 23 , 24 The self-reported strict GFD for at least 1 year and for 16 years on average was checked on site and the patients were found to be symptom free and they were also tested and shown to be negative for serum TG2 antibodies (GFD group). These patients were challenged, that is, consumed 2–4 g of gluten daily for 10 weeks (PGC group).…”

“…Because mucosal damage is dose- and time-dependent, 13 , 21 , 22 and because patients have different levels of gluten consumption at the time of their initial diagnoses, often large amount for decades, these confounding factors may lead to inconsistent results. To circumvent these shortcomings, we sought to exploit the gluten challenge study design 13 , 21 , 22 , 23 , 24 and perform genome-wide transcriptomic analyses of celiac disease small intestinal biopsies from patients on a strict long-term GFD and compare the results with those of biopsies taken from the same celiac disease patients after a standard amount and time on a gluten challenge. We further compared these transcriptomic results with those obtained from non–celiac disease control (DC) patient biopsies.…”

Comprehensive proteomics analyses identify PIM kinases as key regulators of IL-15 driven activation of intestinal intraepithelial lymphocytes

“…Hence, there is an urgent need for treatments for CeD, RCeD, and associated lymphomas. Currently, IL-15 blocking antibodies are being investigated as a treatment strategy (Vicari et al, 2017), however, with limited success (Cellier et al, 2019;Lähdeaho et al, 2019), thus identification of new targets for small molecule inhibitors would be beneficial. Our data suggest that inhibitors against the PIM kinases may also be suitable targets for the treatment of CeD and RCeD.…”