Hilary Jericho, MD

Abstract

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in m), crypt depth (CrD, in m), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400-705) than controls (900, IQR: 667-1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 m (IQR: 390-620) vs. 427 m (IQR: 348-569, p = 0176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

View details for DOI 10.3390/nu14122487

View details for Web of Science ID 000817590300001

View details for PubMedID 35745217

View details for PubMedCentralID PMC9230100

View details for DOI 10.1097/PG9.0000000000000074

Abstract

An expanding gluten-free marketplace has left children with celiac disease and their families with a host of new dietary options. The quality of these foods is inconsistent and processed items may be high in caloric content while lacking nutritional value. Assessing the dietary preferences of a cohort of children with celiac disease via cross-sectional survey, we find that these processed food items have become a staple of the gluten-free diet, and in many cases, these foods are consumed to the exclusion of healthy alternatives. Furthermore, children with celiac disease and their families become less interested in dietary education over time, indicating that the greatest opportunity for imparting a healthy diet may occur at the time of diagnosis.

View details for DOI 10.1097/MPG.0000000000002831

View details for Web of Science ID 000589822800038

View details for PubMedID 32960543

Abstract

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.

View details for DOI 10.3390/nu12061547

View details for PubMedID 32466557

View details for PubMedCentralID PMC7352316

Abstract

The aim of the study was to determine the effects of the gluten-free diet (GFD) on body mass indexes (BMIs) in children with celiac disease at University of Chicago before and after 2011, when processed gluten-free foods became readily available on the market.We conducted a retrospective chart review of children seen at University of Chicago Celiac Center from January 2002 to May 2016. BMI was recorded upon GFD initiation in addition to at least 1 other timepoint: 6 months, 1 year, 2 years, 3 years, and 4+ years. We compared the rate of BMI increase in children who were diagnosed before versus after 2011.A total of 147 children (66% girls) with biopsy-confirmed celiac disease were included in the study. The mean BMI at diagnosis was 17.8 (standard deviation 3.9) for those diagnosed before 2011 and 17.1 (standard deviation 2.7) for those diagnosed after 2011. Based on a mixed-effects random-intercept random-slope regression model, there was no evidence for significant difference in BMI change over time between the 2 groups (P value=0.36). BMI values overall were noted to increase after starting the GFD, even at the first appointment. Serologies were monitored after patients started the GFD and approached normal values, allowing us to conclude that patients were adherent to the GFD.Although overall we observed no significant changes in BMI before and after 2011, we did notice that in adolescent celiac patients there was a trend toward a higher postdiagnosis BMI in the years after 2011. We speculate that teenagers may be especially vulnerable to choosing quick and easy processed gluten-free options over more healthy, natural alternatives leading to a rise in their BMIs after the 2011 surge in production of processed gluten-free foods on the market. Therefore, special attention must be paid to this population to insure ongoing healthy food choices even after many years on the GFD.

View details for DOI 10.1097/MPG.0000000000002190

View details for PubMedID 30801395

Abstract

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 V4+/V1+ intraepithelial lymphocytes (IELs) with innate cytolytic properties and specificity forthe butyrophilin-like (BTNL) molecules BTNL3/BTNL8. Creation of a new niche with reduced expression of BTNL8 and loss of V4+/V1+ IELs was accompanied by the expansion of gluten-sensitive, interferon--producing V1+ IELs bearing Tcell 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 V4+/V1+ subset among TCR+ IELs. Collectively, these data show that chronic inflammation permanently reconfigures the tissue-resident TCR+ IEL compartment in CeD. VIDEO ABSTRACT.

View details for DOI 10.1016/j.cell.2018.12.039

View details for PubMedID 30739797

View details for PubMedCentralID PMC6667191

Abstract

The aim of the study was to evaluate the efficacy of the gluten-free diet (GFD) on gastrointestinal (GI) and extra-intestinal (EI) symptom resolution and identify predictors for persistence of symptoms in all celiac patients at the University of Chicago.We conducted a retrospective chart review from 2002 to 2015. GI symptoms included abdominal pain, bloating, constipation, diarrhea, failure to thrive/weight loss, nausea, reflux, and vomiting. EI symptoms included abnormal liver enzymes, arthralgia/arthritis, dermatitis herpetiformis, alopecia, fatigue, headache, anemia, stomatitis, myalgia, psychiatric disorders, rashes, seizures, neuropathy, short stature, delayed puberty, osteoporosis, and infertility.A total of 554 patients (227 children) with celiac disease (CeD) were included. Abdominal pain, diarrhea and failure to thrive were the most common GI symptoms in children whereas diarrhea, bloating, and abdominal pain were most common in adults. Short stature, fatigue, and headache were the most common EI symptoms in children whereas iron deficiency anemia, fatigue, and headache/psychiatric disorders were most common in adults. Children had significantly higher rates of EI and GI symptom resolution as compared to adults, with greater rates of improvements in GI versus EI symptoms at more than 24 months. Long duration of symptoms, female sex, and non-adherence to a GFD were the most important significant predictors of failure to clinically improve.On a strict GFD, children report greater rates of both GI and EI symptom resolution as compared to adults with greater rates of improvement in GI over EI symptoms. Early recognition of CeD and close attention to diet adherence may help in symptom resolution.

View details for DOI 10.1097/MPG.0000000000001634

View details for PubMedID 28514243

Abstract

The aim of the study was to evaluate the effectiveness of the gluten-free diet (GFD) on extraintestinal symptoms in pediatric and adult celiac populations at the University of Chicago.We conducted a retrospective chart review of the University of Chicago Celiac Center clinic charts from January 2002 to October 2014. Demographics, serologic testing, intestinal biopsies, and extraintestinal symptoms at presentation, 12, 24, and >24 months were recorded. Extraintestinal symptoms included abnormal liver enzymes, arthralgia/arthritis, dermatitis herpetiformis, alopecia, fatigue, headache, anemia, stomatitis, myalgias, psychiatric disorders, rashes, seizures, neuropathy, short stature, delayed puberty, osteoporosis, and infertility.A total of 737 patients with biopsy-confirmed celiac disease or skin biopsy-confirmed dermatitis herpetiformis were included. Patients lost to follow-up, or with insufficient data were excluded leaving 328 patients (157 pediatrics younger than 18 years). For pediatrics, the female to male ratio was 2:1 and the mean age at diagnosis was 8.9 years. For adults, 4:1 and 40.6 years old. Extraintestinal symptom rates were similar in children (60%) and adults (62%). Short stature (33%), fatigue (28%), and headache (20%) were most common in children. Iron deficiency anemia (48%), fatigue (37%), and headache/psychiatric disorders (24%) were common in adults. Children had faster/higher rates of symptom resolution compared with adults. Twenty-eight percent of children with unresolved short stature on a GFD were found to have other comorbidities.Children and adults with celiac disease have similar rates of extraintestinal manifestations. In children short stature, fatigue, and headache were most common, whereas anemia, fatigue, and headache/psychiatric disorders were most common in adults. Children on a strict GFD showed faster and higher rates of symptom resolution as compared to adults. Unresponsive children with short stature must be assessed for comorbidities.

View details for DOI 10.1097/MPG.0000000000001420

View details for Web of Science ID 000404960900025

View details for PubMedID 28644353