Chronic inflammation permanently reshapes tissue-resident immunity in celiac disease

Tissue-resident lymphocytes play a key role in immune surveillance, but it remains unclear how these inherently stable cell populations respond to chronic inflammation. In the setting of celiac disease (CeD), where exposure to dietary antigen can be controlled, gluten-induced inflammation triggered a profound depletion of naturally occurring Vγ4+/Vδ1+ intraepithelial lymphocytes (IELs) with innate cytolytic properties and specificity for the butyrophilin-like (BTNL) molecules BTNL3/BTNL8. Creation of a new niche with reduced expression of BTNL8 and loss of Vγ4+/Vδ1+ IELs was accompanied by the expansion of gluten-sensitive, interferon-γ-producing Vδ1+ IELs bearing T cell receptors (TCRs) with a shared non-germline-encoded motif that failed to recognize BTNL3/BTNL8. Exclusion of dietary gluten restored BTNL8 expression but was insufficient to reconstitute the physiological Vγ4+/Vδ1+ subset among TCRγδ+ IELs. Collectively, these data show that chronic inflammation permanently reconfigures the tissue-resident TCRγδ+ IEL compartment in CeD

Extra-Intestinal Manifestation of Celiac Disease in Children

The aim of this literature review is to discuss the extra-intestinal manifestations of celiac disease within the pediatric celiac population

Extra-Intestinal Manifestation of Celiac Disease in Children

The aim of this literature review is to discuss the extra-intestinal manifestations of celiac disease within the pediatric celiac population

Nausea predicts delayed gastric emptying in children

To assess whether the gastroparesis cardinal symptom index (GCSI), or any individual symptom, is associated with delayed gastric emptying in children, and to assess understanding of symptoms associated with delayed gastric emptying. Fifty children (36 F), 5-18 years of age, undergoing gastric emptying scintigraphy (GES) at Lurie Children's Hospital in Chicago, Illinois, completed Likert-type GCSI and symptom comprehension questionnaires. Correlation of GES results (normal or abnormal) with questionnaire results using the Wilcoxon rank sum test. Seventy percent of subjects had a normal GES. Children reported understanding most terms of GCSI (average score 2.59, range 0-3). The GCSI was not associated with delayed gastric emptying. Nausea was associated with delayed gastric emptying only (numerical P = .04, word P = .02). Results were not altered when poorly understood terms were excluded. The GCSI is not associated with delayed gastric emptying in children. Lack of association does not seem to be related to lack of understanding. Nausea alone was the only symptom that showed an association with delayed gastric emptying on GES

The Gluten Free Diet's Impact on Growth in Children with Celiac Disease in Two Different Countries

The effects of gluten free diet (GFD) on body mass index (BMI) and growth parameters in pediatric patients with celiac disease (CD) and their dependence on different socio-cultural environments are poorly known. We conducted an international retrospective study on celiac patients diagnosed at the University of Verona, Italy, and at the University of Chicago, Chicago, IL, USA, as underweight. A total of 140 celiac children and 140 controls (mean age 8.4 years) were enrolled in Chicago; 125 celiac children and 125 controls (mean age 7.3 years, NS) in Verona. At time of diagnosis, Italian celiac children had a weight slightly lower (p= 0.060) and a BMI z-score significantly (p< 0.001) lower than their American counterparts. On GFD, Italian celiac children showed an increased prevalence of both underweight (19%) as well as overweight (9%), while American children showed a decrease prevalence of overweight/obese. We concluded that while the GFD had a similar impact on growth of celiac children in both countries, the BMI z-score rose more in American than in Italian celiac children. Additionally, in Italy, there was an alarming increase in the proportion of celiac children becoming underweight. We speculate that lifestyle and cultural differences may explain the observed variations

Bile Acid Pool Dynamics in Progressive Familial lntrahepatic Cholestasis With Partial External Bile Diversion

Objectives: Partial external bile diversion (PEBD) is an established therapy for low-gamma-glutamyl transferase (GGT) progressive familial intrahepatic cholestasis (PFIC). This study sought to determine whether the dynamics of the cholic acid (CA) and chenodeoxycholic acid (CDCA) pools in subjects with low-GGT-PFIC with successful PEBD were equivalent to those achieved with successful liver transplantation (LTX). Methods: The kinetics of CA and CDCA metabolism were measured by stable isotope dilution in plasma samples in 5 subjects with PEBD, all with intact canalicular bile salt export pump expression and compared with subjects with low-GGT-PFIC with successful LTX. Stomal loss of bile acids was measured in subjects with PEBD. Results: The fractional turnover rate for CA in the PEBD group ranged from 0.5 to 4.2/day (LTX group, range 0.2-0.9/day, P = 0.076) and for CDCA from 0.7 to 4.5/day (LTX group 0.3-0.4/day, P = 0.009). The CA and CDCA pool sizes were equivalent between groups; however, pool composition in PEBD was somewhat more hydrophilic. The CA/CDCA ratio in PEBD ranged from 0.9 to 49.5, whereas in LTX it ranged from 0.5 to 2.6. Synthesis rates computed from isotope dilution correlated well with timed output for both CA (r(2) = 0.760, P = 0.024) and CDCA (r(2) = 0.690, P=0.021). Conclusions: PEBD results in bile acid fractional turnover rates greater than LTX, pool sizes equivalent to LTX, and pool composition that is at least as hydrophilic as produced by LTX

GLOBAL TRANSLATION OF COELIAC DISEASE HISTOLOGY AND OTHER GLUTEN RELATED MICROENTEROPATHY

Introduction Intestinal epithelial cell damages generated by inflammation in coeliac disease (CD) ranges from sub-microscopic to severe architectural distortion. Translation of quantitative morphological changes in intestinal microorgans, like villus/crypt transformation, distribution of inflammatory cells and diagnostic cut offs, is lacking for CD and gluten related micro-enteropathies. Method Investigators from 22 centres, 9 countries of 4 continents, recruited CD patients with Marsh 0-II histology (n=299), NCGS (n=151), and 262 controls. Based on an agreed protocol, epithelial morphology including intraepithelial lymphocyte (IEL) density, villus height and crypt depth were measured in well-oriented duodenal biopsies. Results In total 712 subjects were recruited from Australia (20), Finland (20), India (25), Iran (37), Italy (246), Romania (10), Turkey (30), UK (166) and USA (158). Preliminary analyses showed raw IEL density (IEL/100EC) was poorly correlated with tTG, villus height, crypt depth or their ratios, and even significant findings did not show strong correlation coefficients (<0.36). The IEL density cut off scored 93% sensitivity and specificity at 24/100EC for CD. However, for NCGS the optimal sensitivity and specificity cut off was at 22IEL/ 100EC giving a sensitivity of 57% and specificity of 80% (see fig 1). The villus height was significantly shorter in CD compared to either control (p<0.001) or NCGS groups (p<0.001). Also, NCGS had short villus height than control (p<0.001). Conclusion The most specific and strongest biomarker for CD with microenteropathy is serology acting as the gold standard in this group. Villus height and crypt depth would serve as complementary tools in diagnosis of mild CD and NCGS patients. NCGS seem to have a milder morphological change compared to CD even when they present with similar Marsh scores. This study also confirms the cut off of IEL for CD with microenteropathy is similar to CD with severe enteropathy at 25 IEL/100EC