ABSTRACT
Background: Celiac disease (CD) is a chronic immuno-mediated enteropathy caused by dietary gluten in genetically susceptible individuals carrying HLA (Human Leukocytes Antigen) genes that encode for DQ2.5 and DQ8 molecules. TRAFD1 (TRAF-type zinc finger domain 1) is a gene recently found associated with CD and defined as a master regulator of IFNγ signalling and of MHC class I antigen processing/presentation. There is no specific drug therapy and the only effective treatment is the gluten-free diet (GFD). The great majority of celiac patients when compliant with GFD have a complete remission of symptoms and recovery of gut mucosa architecture and function. Until now, very few studies have investigated molecular differences occurring in CD patients upon the GFD therapy. Methods: We looked at the expression of both HLA DQ2.5 and TRAFD1 risk genes in adult patients with acute CD at the time of and in treated patients on GFD. Specifically, we measured by qPCR the HLA-DQ2.5 and TRAFD1 mRNAs on peripheral blood mononuclear cells (PBMC) from the two groups of patients. Results: When we compared the HLA-DQ mRNA expression, we didn't find significant variation between the two groups of patients, thus indicating that GFD patients have the same capability to present gliadin antigens to cognate T cells as patients with active disease. Conversely, TRAFD1 was more expressed in PBMC from treated CD subjects. Notably, TRAFD1 transcripts significantly increased in the patients analyzed longitudinally during the GFD, indicating a role in the downregulation of gluten-induced inflammatory pathways. Conclusion: Our study demonstrated that HLA-DQ2.5 and TRAFD1 molecules are two important mediators of anti-gluten immune response and inflammatory process.
ABSTRACT
BACKGROUND: Gluten-free diet (GFD) is the one therapy in coeliac disease (CeD). Unfortunately, some patients adopt GFD before the diagnostic work-up. The guidelines suggest a 14-day gluten intake > 3 gr to get CeD diagnosis, although many subjects refuse this approach. Other evidence showed that the intake of 50 mg/day of gluten for 3 months could be useful for CeD diagnosis. AIMS: We performed a dietary study, administering a low dose of gluten in form of "crackers" (about 60-120 mg of gluten/day) for 3 months, to get a final diagnosis of CeD in subjects already on GFD. METHODS: We enrolled adult patients with a suspicion of CeD on self-prescribed GFD. All subjects performed the crackers challenge for 3 months. At the end, all patients were analysed for CeD serology and if positive underwent endoscopy/histology. Also, we recorded the grade of satisfaction for the gluten challenge and the onset of adverse events. RESULTS: We enrolled 120 patients. All patients concluded the challenge without relevant adverse events. Serological positivity was detected in 54 patients (45%). Histology showed atrophy in 87% and Marsh 1-2 grade in 13% of patients. Ninety-nine patients (83%) were satisfied by this challenge. CONCLUSIONS: The "crackers challenge" is a useful and safe diagnostic approach in people on self-administered GFD.
ABSTRACT
BACKGROUND: Anti-endomysial antibodies (EMA) and anti-tissue transglutaminases (a-tTg) play a pivotal role in coeliac disease (CD) diagnosis. Deamidated anti-gliadin peptides (DGP) were added to the CD diagnostic workup. AIMS: We aimed to compare the diagnostic accuracies of ELISA-based (a-tTg/DGP) and immunofluorescence-ELISA-based strategies (EMA/a-tTg) for CD diagnosis. METHODS: From November 2020 to November 2022, we undertook an observational prospective study including consecutive adult patients with suspected CD. All subjects were tested for EMA, a-tTg and DGP IgA. An ROC curve was plotted to establish the best specificity cut-off of a-tTg and DGP levels, which would predict the presence of Marsh≥2 and Marsh=3. The diagnostic accuracies of a-tTg/DG and EMA/a-tTg were compared. RESULTS: The study included 275 CD patients. Histology showed Marsh=1 in 9.9%, Marsh=2 in 4.5%, and Marsh=3 in 85.6.%. The best cut-off value of a-tTg for predicting Marsh≥2 was 42 U/mL, while the best cut-off for predicting atrophy was 68.4 U/mL. The best cut-off value of DGP for predicting Marsh≥2 was 56 U/mL, while the best cut-off for predicting atrophy was 78 U/mL. A-tTg/EMA showed 97% sensitivity and 100% specificity, whereas a-tTg/DGP showed 94% sensitivity and 100% specificity. CONCLUSION: A-tTg/DGP is accurate for CD diagnosis and could reduce costs and operator-dependency of EMA. DGP, together with a-tTg, could replace EMA in CD diagnosis.
Subject(s)
Celiac Disease , Enzyme-Linked Immunosorbent Assay , Gliadin , Transglutaminases , Humans , Celiac Disease/diagnosis , Gliadin/immunology , Male , Female , Adult , Enzyme-Linked Immunosorbent Assay/methods , Prospective Studies , Transglutaminases/immunology , Middle Aged , Sensitivity and Specificity , Autoantibodies/blood , ROC Curve , Immunoglobulin A/blood , Aged , Young AdultABSTRACT
BACKGROUND: Ulcerative colitis [UC] assessment still requires ileocolonoscopy [IC]. Intestinal ultrasound [IUS] has emerged as a non-invasive assessment tool, and the Milan Ultrasound Criteria [MUC] score has been validated to estimate and grade UC disease activity. Recently, hand-held IUS [HHIUS] has been used in several clinical settings, but data about its use in UC are limited. We aimed to evaluate the diagnostic accuracy of HHIUS compared with conventional IUS in detecting UC extension and activity. PATIENTS AND METHODS: From November 2021 to September 2022, we prospectively enrolled UC patients afferent to our third-level IBD Unit for IC evaluation. Patients underwent IC, HHIUS, and IUS. Ultrasound activity was defined by MUCâ >6.2, and endoscopic activity was defined by a Mayo endoscopic score [MES]â >1. Cohen's k test was applied to test the concordance between IUS-MUC and HHIUS-MUC after MUC dichotomisation [MUCâ >6.2, yes/no]. RESULTS: In all, 86 patients with UC were enrolled. No significant difference was recorded between IUS and HHIUS at the per-segment extension [pâ =â N.S.], and both procedures were comparable in terms of results of bowel wall thickness [BWT] and bowel wall stratification [BWS] assessment [pâ =â N.S.]. IUS and HHIUS displayed excellent agreement when the MUC score system was applied [kâ =â 0.86, pâ <0.01]. CONCLUSION: Hand-held intestinal ultrasound and IUS are comparable in UC extension definition and MUC evaluation. HHIUS could be reliable for detecting disease activity and estimating its extension, providing close monitoring. It also represents a non-invasive, easily practicable investigation, allowing immediate medical decisions with significant time and cost advantages.