A Canadian Study toward Changing Local Practice in the Diagnosis of Pediatric Celiac Disease

Abstract

Background. The European Society for Pediatric Gastroenterology, Hepatology and Nutrition endorses serological diagnosis (SD) for pediatric celiac disease (CD). The objective of this study was to pilot SD and to prospectively evaluate gastrointestinal permeability and mucosal inflammation at diagnosis and after one year on the gluten-free diet (GFD). We hypothesized that SD would be associated with similar short term outcomes as ED. Method. Children, 3–17 years of age, referred for possible CD were eligible for SD given aTTG level ≥200 U/mL, confirmed by repeat aTTG and HLA haplotypes. Gastrointestinal permeability, assessed using sugar probes, and inflammation, assessed using fecal calprotectin (FC), at baseline and after one year on a GFD were compared to patients who had ED. Results. Enrolled SD (n = 40) and ED (n = 48) patients had similar demographics. ED and SD groups were not different in baseline lactulose: mannitol ratio (L : M) (0.049 versus 0.034; p = 0.07), fractional excretion of sucrose (%FES; 0.086 versus 0.092; p = 0.44), or fecal calprotectin (FC; 89.6 versus 51.4; p = 0.05). At follow-up, urine permeability improved and was similar between groups, L : M (0.022 versus 0.025; p = 0.55) and %FES (0.040 versus 0.047; p = 0.87) (p > 0.05). FC improved but remained higher in the SD group (37.1 versus 15.9; p = 0.04). Conclusion. Patients on the GFD showed improved intestinal permeability and mucosal inflammation regardless of diagnostic strategy. This prospective study supports that children diagnosed by SD have resolving mucosal disease early after commencing a GFD.

A Survey of Fecal Calprotectin in Children with Newly Diagnosed Celiac Disease with Villous Atrophy

“…Intestinal atrophy seems to be a dominant feature influencing the FC levels in CD patients (15). Here, we detected markedly higher FC levels in the patients that all had villous atrophy (Marsh score 3) while previous reports incorporated children with lower Marsh scores (4,11,15). However, FC was associated with neither the grade of intestinal inflammation nor with the clinical picture of CD in a report by Montalto et al (17).…”

“…In comparison, no significant association was detected between FC and Marsh score, clinical symptoms, or anti-tTG titer in adults with CD (18). The levels of FC were higher in serologically diagnosed children (89.6 µg/g) than in histologically diagnosed children (51.4 µg/g), indicating a potential correlation between the FC levels and IgA anti-tTG titer (4). The levels of FC can be influenced by the clinical picture of CD as symptomatic children may show higher FC levels than children with no signs and symptoms (19).…”

“…Being highly invasive in nature, using sensitive screening markers is not amenable by intestinal biopsies and therefore, it necessitates the application of non-invasive markers. On the other hand, available serological markers of CD can be useful in the diagnosis phase; however, these markers have limitations for predicting relapse or remission during the course of CD (1,4).…”

A single nucleotide polymorphism genetic risk score to aid diagnosis of coeliac disease: a pilot study in clinical care

“…A total of 110 patients, recruited between 2015 and 2017, with adequate sampling and successful genotyping were included in the analysis. Diagnosis of coeliac disease was made by endoscopy (n = 46) or according to a modification of European serological diagnostic guidelines (n = 64) 20 . In this Canadian clinic, patients consenting to serological diagnosis, which is not currently standard of care in North America, were required to have tissue transglutaminase antibody levels greater than 28 times upper limit normal and confirmatory HLA‐DQ typing.…”

The Multiomics Analyses of Fecal Matrix and Its Significance to Coeliac Disease Gut Profiling

“…Biomarkers of protein and peptide in nature are used as both diagnoses and to monitor adherence to a gluten-free diet (GFD) in CeD patients. The biomarkers used to diagnose intestinal diseases are unspecific and focused on monitoring the inflammation status of the GIT, and those biomarkers include calprotectin, immunoglobulin A (IgA) and immunoglobulin G (IgG) [ 231 , 232 , 233 , 234 ]. Recent studies have uncovered the use of specific biomarkers for the sole purpose of isolating and diagnosing CeD pathogenesis, and include immunogenic gluten peptides (specifically 33-mer gliadin peptide) and deamidated gliadin peptides (DGP), as well as antibodies exclusive to CeD subjects only; anti-gliadin antibody (AGA), anti-endomysial antibody (AEA), anti-tissue transglutaminase (anti-tTG–TG2, TG6, TG3) and the neo-epitopes (modification to the antigenic determinant) tTG-DGP complex [ 235 ].…”