Peter H. R. Green

Limited genetic studies on celiac disease (CeD) are available for the Hispanic and black populations. We identified 3,481 individuals with CeD from the All of Us Research Program. Of these, 2,899 carried one of the four well-established risk haplotypes, including 262 of admixed American (89% Hispanic) and 108 of African (70% black) ancestry. An enrichment in the DQB1*02:01 allele was observed in CeD patients across all ancestries, with the strongest association in Europeans (32.3% vs. 11.6%), followed by Americans (18.5% vs. 8.1%) and Africans (15.7% vs. 8.1%). HLA-B8 conferred an additive risk for CeD independent of HLA-DQ2.5 across all three ancestries. The B8-DQ2.5 haplotype was significantly enriched in individuals with CeD but occurred at substantially lower frequencies in individuals with admixed American (3.2%) and African ancestry (1.2%) than in those with European ancestry (7.3%), accounting for ∼34% and 38% of the lower CeD prevalence, respectively. The frequency of the B8-DQ2.5 haplotype contributes to ancestry-dependent differences in CeD prevalence.

The potential utility of genetic testing among individuals with a positive celiac disease (CeD) family history remains limited. We performed whole-exome sequencing in a cohort of 107 cases with CeD and 117 unaffected relatives from 66 families. We assessed fourteen HLA-DQ genotypes, based on combinations of four risk haplotypes. Our cohort was predominantly of European ancestry (87%). Compared with at-risk controls, CeD cases showed a significant enrichment of high-risk (22.4 vs. 10.3%) and moderate-risk (64.4 vs. 35.9%) HLA-DQ genotypes. Stratification based on the weighted impact of fourteen HLA-DQ genotypes yields a more accurate risk assessment than assuming equal contributions from four risk haplotypes. The HLA-B*08:01 allele was more frequent in CeD patients than in controls (32.2 vs. 16.7%). Among individuals of European ancestry, the AH8.1 long haplotype was present in 62% of cases vs. 49% of controls. Whole-exome sequencing enables stratification of first-degree relatives into discrete risk categories, identifying 10% as high risk and ∼50% as having negligible genetic risk.

Background: Most genetic studies on celiac disease (CeD) have focused on individuals of European descent. Limited data are available for the Hispanic and black populations. Methods: We analyzed whole-genome sequencing data, electronic health records (EHR), and laboratory results from the All of Us Research Program. We identified 3,481 individuals with CeD through EHR, self-reporting, or both. Of these, 2,899 carried one of the four well-established risk haplotypes, including 262 of admixed American (89% Hispanic) and 108 of African (70% black) ancestry. Five sex-, age-, and ancestry-matched controls per case were selected for the assessment of genetic and clinical risk factors. Results: An enrichment in the DQB1*02:01 allele was observed in CeD patients across all ancestries, with the strongest association in Europeans (32.3% vs. 11.6%), followed by Americans (18.5% vs. 8.1%) and Africans (15.7% vs. 8.1%). Among individuals carrying the DQ2.5 ( DQA1*05:01-DQB1*02:01 haplotype), HLA-B8 was present in 72.3% of Europeans, 42.3% of Admixed Americans, and lower in Africans. This linkage disequilibrium was higher in CeD patients than in controls across all three ancestries. A polygenic risk score distinguished seropositive CeD from controls with 86% accuracy. Incorporating clinical risk factors, including family history, hypothyroidism, diarrhea, vitamin D deficiency, and anemia, increased predictive accuracy to 92%. The model identified 93% of CeD patients with tTG-IgA levels greater than 10 IU/mL. Conclusion: Linkage between HLA-B8 and DQ2.5 differs significantly among individuals of European, admixed American, and African ancestry, contributing to ancestry-dependent genetic risk for CeD. Summary: Using data from the All of Us Research Program , we found that HLA-DQ2.5, a key genetic risk factor for celiac disease, is present in European (11.6%), Admixed American (8.1%), and African (8.1%) populations, but its disease penetrance differs significantly by ancestry.

Background: The only treatment for Celiac Disease (CeD), which affects about 1% of the population, is a gluten-free diet (GFD). Studies have indicated an association between the GFD, a diminished quality of life (QOL), and maladaptive eating patterns. This study aims to explore food avoidance behaviors in adults with CeD. Methods: This cross-sectional study assessed 50 adults with biopsy-confirmed CeD who completed validated surveys evaluating demographics, psychological factors, QOL, eating pathology, and food avoidance. Results: Overall CDQOL scores were good (mean: 62.7 out of 100). However, 58.0% of the participants self-elected to avoid one or more additional foods without diagnosed allergies or intolerances. Those avoiding one or more other foods had lower QOL scores (57.4 (23.2) vs. 70.2 (15.9)) compared to those only avoiding gluten (p = 0.034). The mean depression score (CESD) for the group avoiding foods beyond gluten was in the depressive range, unlike those avoiding only gluten (16.0 (4.9) vs. 13.6 (4.0), p = 0.078), with 77% of those avoiding more than gluten scoring above the CESD cut-off point of 15, indicating clinical depression. Conclusions: Over half of participants (58%) reported avoiding additional foods beyond the GFD, a behavior associated with decreased QOL and increased depression.

Celiac disease (CeD) is a common autoimmune condition, with a prevalence of ~1%. Currently, a gluten-free diet (GFD) is the only treatment option. Due to fortification rules excluding gluten-free products in the United States of America (U.S.A.), understanding the nutritional adequacy of a GFD is important for promoting optimal health among those with CeD. Cross-sectional examination of multiple 24 h dietary recalls from a study sample of 50 adults and 30 teens with CeD was used to determine nutritional adequacy and excesses according to U.S.A. recommendations. The results were compared with those of 15,777 adults and 2296 teens from a nationally representative sample not reporting CeD, the National Health and Nutrition Examination Survey (NHANES) 2009–2014. Compared with NHANES, our study population was more at risk of low folate and carbohydrate (adults) consumption, and of excessive niacin and vitamin A (teens), as well as saturated and total fat consumption (adults). Overall, though, compared with NHANES, our study participants had similar nutrient concerns but fewer nutritional imbalances, with some notable exceptions. In addition to maintaining a GFD, individuals with CeD should be counseled to maintain a balanced diet and to pay attention to nutrient-dense foods. Special attention should be given to teens in providing dietary counseling to potentially mitigate the risk of future morbidity.

INTRODUCTION: Persistent villous atrophy (VA) is not uncommon in celiac disease (CeD) while patients take a gluten-free diet (GFD). METHODS: We conducted a retrospective study with 122 serum samples collected from controls and patients with CeD either at the initial diagnosis or at the follow-up during endoscopy. These samples were assigned to 3 groups: nonceliac control, non-VA CeD (Marsh score 0–2), and VA CeD (Marsh score 3a-3c). We established an in-house multiplex assay to identify potential serological biomarkers for VA. We assessed autoantibodies reported to affect the small intestine, including IgA and IgG antibodies against tissue transglutaminase (tTG), interferons, villin, actin, autoimmune enteropathy-related 75 kDa antigen (AIE-75), and tryptophan hydroxylase (TPH)-1, as well as 27 cytokines. The apolipoproteins quantified included apo A1, apo B-100, and apo A4, which were produced predominantly by the intestinal epithelium or expressed specifically in villi. RESULTS: Autoantibody levels were high only for tTG antibodies, which performed well in initial CeD diagnosis, but suboptimally for VA prediction during follow-up, because 14.6% of the follow-up patients with VA had low tTG-IgA. Increasing dilution improved tTG-IgA quantification, particularly when the antibody levels were extremely high but did not significantly improve VA detection. Among those with low tTG-IgA and persistent VA, high proinflammatory cytokines were observed in 2 patients. Median low-density lipoprotein cholesterol levels were significantly lower in the VA CeD group (P = 0.03). Apolipoprotein levels were similar in patients with and without VA but diverged between those on a GFD or not. DISCUSSION: tTG-IgA as a biomarker is suboptimal for VA prediction while on a GFD. Persistent VA is associated with low low-density lipoprotein cholesterol levels and partially related to persistent high proinflammatory cytokines.

Celiac disease (CD) is an autoimmune disease in which intestinal inflammation is induced by dietary gluten. The means through which gluten-specific CD4 ⁺ T cell activation culminates in intraepithelial T cell (T-IEL)–mediated intestinal damage remain unclear. Here, we performed multiplexed single-cell analysis of intestinal and gluten-induced peripheral blood T cells from patients in different CD states and healthy controls. Untreated, active, and potential CD were associated with an enrichment of activated intestinal T cell populations, including CD4 ⁺ follicular T helper (T _FH ) cells, regulatory T cells (T _regs ), and natural CD8 ⁺ αβ and γδ T-IELs. Natural CD8 ⁺ αβ and γδ T-IELs expressing activating natural killer cell receptors (NKRs) exhibited a distinct TCR repertoire in CD and persisted in patients on a gluten-free diet without intestinal inflammation. Our data further show that NKR-expressing cytotoxic cells, which appear to mediate intestinal damage in CD, arise from a distinct NKR-expressing memory population of T-IELs. After gluten ingestion, both αβ and γδ T cell clones from this memory population of T-IELs circulated systemically along with gluten-specific CD4 ⁺ T cells and assumed a cytotoxic and activating NKR-expressing phenotype. Collectively, these findings suggest that cytotoxic T cells in CD are rapidly mobilized in parallel with gluten-specific CD4 ⁺ T cells after gluten ingestion.

Celiac disease (CD) is a chronic autoimmune disorder that affects the small intestine in genetically predisposed individuals. Previous studies have investigated the potential link between CD and cardiovascular disease (CVD); however, the findings have been inconsistent. We aimed to provide an updated review of the literature on the association between CD and CVD. PubMed was searched from inception to January 2023 using keywords including CD, cardiovascular disease, coronary artery disease, cardiac arrhythmia, heart failure, cardiomyopathy, and myocarditis. We summarized the results of the studies, including meta-analyses and original investigations, and presented them according to the different forms of CVD. Meta-analyses published in 2015 provided mixed results regarding the relationship between CD and CVD. However, subsequent original investigations have shed new light on this association. Recent studies indicate that individuals with CD are at a higher risk of developing overall CVD, including an increased risk of myocardial infarction and atrial fibrillation. However, the link between CD and stroke is less established. Further research is needed to determine the link between CD and other cardiac arrhythmias, such as ventricular arrhythmia. Moreover, the relationship between CD and cardiomyopathy or heart failure, as well as myopericarditis, remains ambiguous. CD patients have a lower prevalence of traditional cardiac risk factors, such as smoking, hypertension, hyperlipidemia, and obesity. Therefore, it is important to discover strategies to identify patients at risk and reduce the risk of CVD in CD populations. Lastly, it is unclear whether adherence to a gluten-free diet can diminish or increase the risk of CVD among individuals with CD, necessitating further research in this area. To fully comprehend the correlation between CD and CVD and to determine the optimal prevention strategies for CVD in individuals with CD, additional research is necessary.

Background The only treatment for celiac disease (CeD) is strict lifelong adherence to a gluten-free diet (GFD). In some individuals the demands of a GFD may contribute to maladaptive eating attitudes and behaviors that impair quality of life (QOL). The Celiac Disease Food Attitudes and Behaviors (CD-FAB) is an easily administered and scored 11-item tool querying potentially maladaptive food attitudes and behaviors resulting from beliefs around gluten exposures and food safety. Objectives To assess the usefulness of the CD-FAB in establishing the presence of maladaptive food attitudes and behaviors among adults with CeD and to explore the relationship between these attitudes and behaviors and other factors including QOL, anxiety, depression, CeD symptoms and personality traits. Methods The study is a cross-sectional pilot of 50 adults (mean age 29.6 years) with biopsy-proven CeD who followed a GFD for at least one year and had no self-reported eating disorder diagnosis. High scores on the CD-FAB tool suggest higher disordered eating attitudes and beliefs. Results Compared to lower scores (mean 20.2), higher (worse) CD-FAB scores (mean 54.5) were positively associated with recency of diagnosis, number of CeD-related gastrointestinal symptoms, and the personality trait of neuroticism. Higher CD-FAB scores were statistically and clinically significantly associated with diminished QOL (p < 0.001). The relationship with anxiety and depression was less clear but trended in the expected direction. Conclusion The CD-FAB may be a useful tool for dietitians who wish to monitor maladaptive food attitudes and behaviors among their CeD patients, especially in the first-year post-diagnosis.