Human intestinal organoids: Modeling gastrointestinal physiology and immunopathology - current applications and limitations.

Human intestinal organoids are an ideal model system for studying gastrointestinal physiology and immunopathology. Altered physiology and mucosal immune response are hallmarks of numerous intestinal functional and inflammatory diseases, including inflammatory bowel disease (IBD), coeliac disease, irritable bowel syndrome (IBS), and obesity. These conditions impact the normal epithelial functions of the intestine, such as absorption, barrier function, secretion, and host-microbiome communication. They are accompanied by characteristic intestinal symptoms and have significant societal, economic, and healthcare burdens. To develop new treatment options, cutting-edge research is required to investigate their etiology and pathology. Human intestinal organoids derived from patient tissue recapitulate the key physiological and immunopathological aspects of these conditions, providing a promising platform for elucidating disease mechanisms. This review will summarize recent reports on patient-derived human small intestinal and colonic organoids and highlight how these models have been used to study intestinal epithelial functions in the context of inflammation, altered physiology, and immune response. Furthermore, it will elaborate on the various organoid systems in use and the techniques/assays currently available to study epithelial functions. Finally, it will conclude by discussing the limitations and future perspectives of organoid technology.

Clinical outcomes of potential coeliac disease: a systematic review and meta-analysis.

OBJECTIVE: Potential coeliac disease (PCD) is characterised by positive serological and genetic markers of coeliac disease with architecturally preserved duodenal mucosa. The clinical outcomes and rates of progression to overt coeliac disease in patients with PCD remain uncertain. In this systematic review and meta-analysis, we aimed to evaluate the clinical outcomes of patients with PCD. DESIGN: We searched Medline, Embase, Scopus and Cochrane Library from 1991 through May 2024 to identify studies evaluating the clinical outcomes of patients with PCD. The progression rates to villous atrophy, seroconversion and response to a gluten-free diet (GFD) were analysed. A random-effect meta-analysis was performed, and the results were reported as pooled proportions with 95% CIs. RESULTS: Seventeen studies comprising 1010 patients with PCD were included in the final analyses. The pooled prevalence of PCD among patients with suspected coeliac disease was 16% (95% CI 10% to 22%). The duration of follow-up in most of the studies was at least 1 year, with follow-up periods within individual studies ranging from 5 months to 13 years. During follow-up, 33% (95% CI 18% to 48%; I2=96.4%) of patients with PCD on a gluten-containing diet developed villous atrophy, and 33% (95% CI 17% to 48%; I2=93.0%) had normalisation of serology. Among those who adhered to a GFD, 88% (95% CI 79% to 97%; I2=93.2%) reported symptomatic improvement. CONCLUSION: Almost a third of patients with PCD develop villous atrophy over time, whereas a similar proportion experience normalisation of serology despite a gluten-containing diet. Most symptomatic patients benefit from a GFD. These findings highlight the importance of structured follow-up and individualised management for patients with PCD.

Coeliac disease: the paradox of diagnosing a food hypersensitivity disorder with autoantibodies.

Serum antibodies to the autoantigen transglutaminase 2 (TG2) are increasingly harnessed to diagnose coeliac disease. Diagnostic guidelines for children give recommendation for a no-biopsy-based diagnosis through detection of high amounts of IgA anti-TG2 antibodies in serum with confirmation of positivity in a separate blood sample by characteristic autoantibody-staining of tissue. While measurement of IgA anti-TG2 also is important in the diagnostic workup of adults, the adult guidelines still mandate examination of gut biopsies. This requirement might well change in the future, as might the necessity for confirming autoantibody positivity by tissue staining. The key role of autoantibody serology for diagnosis of coeliac disease is paradoxical. Coeliac disease was considered, and still can be considered, a food intolerance disorder where autoantibodies at face value are out of place. The immunological mechanisms underlying the formation of autoantibodies in response to gluten exposure have been dissected. This review presents the current insights demonstrating that the autoantibodies in coeliac disease are intimately integrated in the maladapted immune response to gluten.

New entity of adult ultra-short coeliac disease: the first international cohort and case-control study.

BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.

Coeliac disease and type 2 diabetes risk: a nationwide matched cohort and Mendelian randomisation study.

AIMS/HYPOTHESIS: While the association between coeliac disease and type 1 diabetes is well documented, the association of coeliac disease with type 2 diabetes risk remains undetermined. We conducted a nationwide cohort and Mendelian randomisation analysis to investigate this link. METHODS: This nationwide matched cohort used data from the Swedish ESPRESSO cohort including 46,150 individuals with coeliac disease and 219,763 matched individuals in the comparator group selected from the general population, followed up from 1969 to 2021. Data from 9053 individuals with coeliac disease who underwent a second biopsy were used to examine the association between persistent villous atrophy and type 2 diabetes. Multivariable Cox regression was employed to estimate the associations. In Mendelian randomisation analysis, 37 independent genetic variants associated with clinically diagnosed coeliac disease at p<5×10-8 were used to proxy genetic liability to coeliac disease. Summary-level data for type 2 diabetes were obtained from the DIAGRAM consortium (80,154 cases) and the FinnGen study (42,593 cases). RESULTS: Over a median 15.7 years' follow-up, there were 6132 (13.3%) and 30,138 (13.7%) incident cases of type 2 diabetes in people with coeliac disease and comparator individuals, respectively. Those with coeliac disease were not at increased risk of incident type 2 diabetes with an HR of 1.00 (95% CI 0.97, 1.03) compared with comparator individuals. Persistent villous atrophy was not associated with an increased risk of type 2 diabetes compared with mucosal healing among participants with coeliac disease (HR 1.02, 95% CI 0.90, 1.16). Genetic liability to coeliac disease was not associated with type 2 diabetes in DIAGRAM (OR 1.01, 95% CI 0.99, 1.03) or in FinnGen (OR 1.01, 95% CI 0.99-1.04). CONCLUSIONS/INTERPRETATION: Coeliac disease was not associated with type 2 diabetes risk.

Bridging science and accessibility: a tactile journey from gluten through to coeliac disease.

As part of the Monash Sensory Science Exhibition, our team guided participants through a multisensory journey unraveling coeliac disease development and pathology. Through tactile and sensory exhibits, we showed how benign dietary gluten can be transformed into a harmful entity for the 1 in 70 Australians with this illness. In contrast to the common misconception of coeliac disease as a food allergy, our exhibits revealed its closer association with autoimmune diseases such as type 1 diabetes, involving genetic susceptibility linked to specific human leukocyte antigens, crucial antigen-specific T- and B-cell responses and autoantibody production. Tactile models underscored the severe consequences of the proinflammatory immune response to gluten on patient health and quality of life. This educational event affirmed to us the value and importance of fostering inclusivity in science education.

Foetal gluten immunogenic peptides during pregnancy: a new determinant on the coeliac exposome.

BACKGROUND: The increasing incidence of coeliac disease is leading to a growing interest in active search for associated factors, even the intrauterine and early life. The exposome approach to disease encompasses a life course perspective from conception onwards has recently been highlighted. Knowledge of early exposure to gluten immunogenic peptides (GIP) in utero could challenge the chronology of early prenatal tolerance or inflammation, rather than after the infant's solid diet after birth. METHODS: We developed an accurate and specific immunoassay to detect GIP in amniotic fluid (AF) and studied their accumulates, excretion dynamics and foetal exposure resulting from AF swallowing. One hundred twenty-five pregnant women with different gluten diets and gestational ages were recruited. RESULTS: GIP were detectable in AF from at least the 16th gestational week in gluten-consuming women. Although no significant differences in GIP levels were observed during gestation, amniotic GIP late pregnancy was not altered by maternal fasting, suggesting closed-loop entailing foetal swallowing of GIP-containing AF and subsequent excretion via the foetal kidneys. CONCLUSIONS: The study shows evidence, for the first time, of the foetal exposure to gluten immunogenic peptides and establishes a positive correlation with maternal gluten intake. The results obtained point to a novel physiological concept as they describe a plausible closed-loop circuit entailing foetal swallowing of GIP contained in AF and its subsequent excretion through the foetal kidneys. The study adds important new information to understanding the coeliac exposome.

Intragastric administration of transamidated gliadin interferes with the systemic and intestinal immune responses to wheat gliadin in DQ8 transgenic mice.

We have previously shown the ability of transamidated gluten (spf) to modulate both innate and adaptive intestinal immunity elicited by wheat gliadin in HLA-DQ8 transgenic mice (DQ8 mice), a model of gluten sensitivity. Herein, we evaluated the influence of spf when administered intragastrically on the immune response to native gliadin in DQ8 mice. To address the issue, we analysed three regimens of antigen administration: before immunisation (pre-treatment), during immunisation (co-treatment) and through breast milk during the lactating phase (suckling treatment). Mice were immunised mucosally by intranasal delivery of digested wheat gliadin along with cholera toxin in multiple doses. After sacrifice, isolated spleen and mesenteric lymph node (MLN) cells were challenged in vitro and the cytokine profile of culture supernatants assessed by ELISA and multiparametric assay. We found that only pre-treatment with spf was effective in down-regulating the gliadin-specific IFN-γ response and only in spleen cells. Interestingly, spf pre-treatment also induced systemic IL-6, IL-17A and TNF-α. By contrast, we found that spf pre-treatment upregulated INF-γ in MLN but also significantly decreased IL-2. In conclusion, our data provide evidence that the preventive intragastric administration of transamidated gluten is able to interfere with the classical cytokine profile induced by gliadin via mucosal immunisation in a transgenic model expressing one of the HLA molecules associated with coeliac disease.

Biological variability of human intraepithelial lymphocytes throughout the human gastrointestinal tract in health and coeliac disease.

BACKGROUND: Intraepithelial lymphocytes are the first line of defence of the human intestinal immune system. Besides, their composition is altered on patients with coeliac disease (CD), so they are considered as biomarkers with utility on their diagnose and/or monitoring. Our aim is to address their variability through the human gastrointestinal tract in health and characterized them in further depth in the coeliac duodenum. METHODS: Intraepithelial lymphocytes were isolated from human gastric, duodenal, ileal and colonic biopsies, then stained with specific antibodies and acquired by flow cytometry. RESULTS: Our results confirmed that the profile of Intraepithelial lymphocytes change through the length of the human gastrointestinal tract. Besides and given the central role that Interleukin-15 (IL-15) elicits on CD pathogenesis; we also assessed the expression of its receptor revealing that there was virtually no functional IL-15 receptor on duodenal Intraepithelial lymphocytes. Nevertheless and contrary to our expectations, the active IL-15 receptor was not increased either on Intraepithelial lymphocytes from CD patients. CONCLUSIONS: IL-15 might require additional stimulus to activate intraepithelial lymphocytes. These findings may provide novel tools to aid on a CD diagnosis and/or monitoring, at the time that provide the bases to perform functional studies in order of getting a deeper insight in the specific function that Intraepithelial lymphocytes elicit on CD pathogenesis.

Clinical utility of the fracture risk assessment tool (FRAX) in biopsy-confirmed coeliac disease.

BACKGROUND: People with coeliac disease (CD) are at increased risk of osteoporosis and fractures. Currently, baseline dual-energy X-ray absorptiometry (DXA) is recommended for all patients with newly diagnosed CD. We aimed to determine the prevalence of osteoporosis and the clinical utility of the Fracture Risk Assessment Tool (FRAX) in predicting major osteoporotic fractures (MOF) in patients with biopsy-proven CD. METHODS: We retrospectively collected data for consecutive adult patients with biopsy-proven CD between 2001 and 2015 who underwent DXA scanning within 1 year of diagnosis and were followed up for a minimum of 7 years. Fracture risk was assessed using FRAX scores, and the incidence of major osteoporotic fractures during the follow-up period was analysed. RESULTS: A total of 593 patients (median age 45.0 years, 68.5% female) were included. The prevalence of osteopenia and osteoporosis were 32.3% and 14.5%, respectively. Increasing age (OR 1.06, p < .0001), decreasing BMI (OR 0.90, p = .003), and higher baseline immunoglobulin A-tissue tissue transglutaminase titre (OR 1.04, p = .03) were significantly associated with increased risk of osteoporosis. The sensitivity, specificity, positive and negative predictive values of the FRAX tool to predict MOF were 21.2%, 91.3%, 16.3%, 93.5%, respectively. A higher risk of fractures was associated with ongoing gluten exposure (OR 1.86, p = .02), previous fractures (OR 2.69, p = .005), and older age (OR 1.03, p < .0001). CONCLUSION: Osteoporosis is a common finding in patients with CD. The FRAX tool showed high specificity in predicting osteoporotic fractures and could be used to aid with patient selection for DXA scanning in some cases.

Uncovering the gap: Coeliac disease knowledge among healthcare professionals in the Danube region.

BACKGROUND: Several studies have shown that the knowledge about coeliac disease (CD) is not satisfactory among healthcare professionals (HCP). The aim of our study was to assess the knowledge of HCPs about CD in the Danube region. METHODS: HCPs from 8 countries in the Danube region were asked to complete the web-based questionnaire about CD. Scores of HCPs were compared according to their speciality, work experience and country of residence. The results were compared with the results of a similar study conducted in Central Europe within the Focus IN CD project in 2016. RESULTS: Questionnaire was completed by 799 HCPs from Austria, Croatia, Czech Republic, Hungary, Moldova, Romania, Serbia, and Slovenia. Mean score achieved by HCPs was 52.2%. Paediatric gastroenterologists scored the highest (75.3%). Comparing the data with the study conducted in Central Europe in 2016, we found a significant rise (p < 0.001) in the knowledge of paediatric gastroenterologists. Also, HCPs who previously took part in the Focus IN CD project, achieved higher score (61.1% vs. 50.8%; p < 0.001). CONCLUSION: The knowledge about CD among HCPs in Danube region is not satisfactory. There has been a significant increase in the knowledge of paediatric gastroenterologists, showing the benefit of various awareness raising activities that were carried out recently.

Early diet and the risk of coeliac disease. An update 2024 position paper by the ESPGHAN special interest group on coeliac disease.

This position paper by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Special Interest Group on Coeliac Disease (SIG-CD) presents an update to the 2016 recommendations concerning early diet and the risk of coeliac disease (CD). This update adheres to the policy that mandates reviewing guidelines every 5 years, particularly when new data emerge. The 2024 statements and recommendations are essentially similar to the 2016 recommendations. Breastfeeding, whether any amount, exclusive, or of any duration, does not reduce the risk of developing CD. Introducing gluten into an infant's diet at any time between completed 4 months (≥17 weeks) and 12 months of age does not affect the cumulative incidence of CD, although earlier introduction may lead to earlier seroconversion and CD. In observational studies involving cohorts with a known risk for CD, consuming a high amount of gluten compared to a low amount during weaning and in the subsequent childhood years-specifically the first 2-3 years, and even up to 5 years in some studies-was associated with an increased risk for CD. However, the specific optimal amounts of gluten consumption remain undetermined due to insufficient evidence on safe thresholds, and the impact of restricting gluten in the diet of healthy children of unknown risk for CD is unknown. Thus, any recommendation on the gluten amount is currently unjustifiable for the general population and infants with known HLA risk types. There is no specific guidance on the type of gluten-containing foods to be introduced at weaning.

Budesonide Induces Favourable Histologic and Symptomatic Recovery in Patients with Non-responsive and Refractory Coeliac Disease When Given in an Open Capsule Format.

INTRODUCTION: Non-responsive coeliac disease (NRCD), where symptoms and enteropathy persist despite a prolonged gluten-free diet (GFD), is common. Refractory coeliac disease (RCD), characterised by malabsorption and extensive enteropathy, is rare but serious. In both, treatment options are limited. Topical budesonide may help and an open capsule format promoting proximal small intestinal delivery may be advantageous. AIM: To describe the effect of budesonide and its presentation on mucosal healing, symptoms, and tolerability in NRCD and RCD. METHODS: A retrospective cohort study of NRCD and RCD patients who received budesonide for enteropathy despite a strict GFD for over 12 months. Primary outcome was improvement in histology. Symptoms and adverse treatment effects were recorded. RESULTS: 50 patients with NRCD (n = 14; 86% F), RCD type 1 (n = 30; 60% F), and RCD type 2 (n = 6 based on aberrant duodenal T cells; 33% F) were identified. Common RCD symptoms were diarrhoea (68%), fatigue (40%), and weight loss (34%). 16 received closed capsule budesonide (CCB) 9 mg OD and 35 open capsule budesonide (OCB) 3 mg 3 times a day. Complete and partial mucosal healing was significantly higher after OCB compared to CCB (p < 0.001, Mann-Whitney U test). Symptom improvement was also significantly higher after OCB compared to CCB (p = 0.002, Mann-Whitney U test). Side effects were mild and self-limiting and were reported in 25% of both cohorts. CONCLUSION: OCB was well tolerated and associated with improvements in enteropathy (83%) and symptoms (90%) in NRCD and RCD. Our findings support OCB as the preferred 1st-line therapy for NRCD and RCD type 1.

The psychosocial experiences of adults diagnosed with coeliac disease: a qualitative evidence synthesis.

BACKGROUND: Coeliac disease is a chronic autoimmune condition associated with intestinal and extraintestinal symptoms. Coeliac Disease is managed through strict adherence to a gluten-free diet, which, though usually effective, is challenging to maintain. This review synthesised qualitative research on the psychosocial experiences of adults living with coeliac disease. METHODS: Keyword searches were conducted of the academic databases CINAHL, EMBASE, MEDLINE, PsychINFO, SCOPUS and Web of Science for articles published (2005-2021), followed by forward and backward searches. Thematic synthesis of included articles was carried out on sections reporting findings or results, discussion, conclusions, and supporting data. The inductive thematic synthesis identified descriptive and analytical themes from the included studies. RESULTS: Of 1284 records identified, 17 articles from 15 original studies were included in the thematic synthesis. The majority of studies were from Europe (76%), with the remainder from North America and Australia. Data represented 371 adults with coeliac disease (72% female; 17-85 years old, diagnosed < 1-42 years ago) across eight countries. Findings identified six analytical themes relating to the psychosocial experience of coeliac disease: 'Living with ongoing risk'; 'Losing more than gluten'; 'A changed identity'; 'A changed relationship with food'; 'The gluten-free diet creates a multifaceted burden'; and 'Learning how to live well with Coeliac Disease'. CONCLUSIONS: Coeliac disease changes adults' psychosocial experiences. Adaptation involves ongoing learning, and development of psychological acceptance facilitates adjustment. Increased public education about coeliac disease may reduce stigma and risk. Psychosocial assessment and support could improve quality of life post-diagnosis.

Transcultural adaptation to Spain of the CDPQOL questionnaire specific for coeliac children.

This study aimed to translate, cross-culturally adapt, and validate the CDPQOL questionnaire, a coeliac disease (CD)-specific paediatric health-related quality of life (HRQoL) instrument (CDPQOL), in Spanish children with CD. The CDPQOL questionnaire has two versions for children aged 8-12 and 13-18. Translation and linguistic validation were performed following an international consensus process. Internal consistency was calculated using Cronbach's alpha and McDonald's omega coefficients, and convergent validity was assessed with average variance extracted (AVE). Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA), when necessary, were carried out to assess the construct validity. A total of 235 children were included. In the 8-12 age group, a change in the distribution of items to a new structure of three dimensions (negative emotions, food feelings and social interaction) was required. In this new model, CFA supported the fit of the model (χ2/gl = 1.79, RMSEA = 0.077 (IC 95% 0.05-0.100), CFI = 0.969, TLI 0.960, SRMR = 0.081) and Cronbach's alpha and McDonald's omega coefficients were > 0.7 in all three dimensions. In the 13-18 age group, CFA showed that all fit indexes were acceptable (χ2/gl = 1.702, RMSEA = 0.102 (IC 95% 0.077-0.127), p < 0.001, CFI = 0.956, TLI = 0.947, SRMR = 0.103) and Cronbach's alpha and McDonald's omega coefficients were > 0.7 in all three dimensions, except for uncertainty dimension. Conclusions: The Spanish version of the CDPQOL questionnaire is a useful instrument to assess quality of life in coeliac children whose native language was Spanish spoken in Spain, with changes in item distribution in the younger age group questionnaire. What is Known: • The first specific questionnaire for coeliac children, Dutch Coeliac Disease Questionnaire (CDDUX), which focuses on diet, was translated into Spanish and validated allowing to evaluate the HRQoL of Spanish coeliac children. • Spanish Children and parents feel the disease had no substantial negative impacts on patient HRQoL using this questionnaire, similar to that observed with other countries. What is New: • The age specific for CD children (CDPQOL) was elaborated in the USA and focuses on other aspects not evaluated by CDDUX such as emotional and social issues related to living with CD. • The CDPQOL was translated into Spanish and validated allowing it to be used to assess Spanish coeliac children's QoL.

With or without biopsy in coeliac children?-Impact on dietary compliance and quality of life.

Critics of the ESPGHAN guidelines on CD question the acceptance of the no-biopsy policy by patients and parents against the backdrop of a lifelong diagnosis. The aim of this study was to investigate the impact of the no-biopsy approach on dietary adherence and health-related quality of life (HRQOL). In this retrospective cohort study, patients ≤ 18 years diagnosed with CD between 2007 and 2017 were sent two questionnaires: a dietary interview and a CD-specific HRQOL questionnaire (CDDUX). Included patients were divided into group A (with biopsies <2012), B (with biopsies >2012) and C (without biopsies >2012). Fisher exact test and ANOVA were used to analyze the impact of the new diagnostic strategy. Forty-seven percent (82/173 patients) consented to participate in the study. Of them, 63% had a biopsy-confirmed diagnosis (40% before 2012 (group A), 23% after 2012 (group B)), and 37% were diagnosed without biopsies (group C). Dietary compliance was similar in all groups (p = 0.67). Group A scored significantly better on the subscale 'Having CD' compared to both groups diagnosed after 2012 (p = 0.003). Group A and group C seemed to score better on the total CDDUCX score when compared to group B (86 and 80% versus 61% respectively, p = 0.13). This was also observed within the subscale Diet; Group A and C scored significantly better than group B (62 and 72% versus 39% respectively, p = 0.09). CONCLUSIONS: Omitting duodenal biopsies in the diagnostic approach of our CD cohort had no adverse effect on dietary adherence and HRQOL. WHAT IS KNOWN: • Since the publication of the ESPGHAN guideline of 2012, duodenal biopsies are no longer obligatory in the diagnostic approach of CD if IgA-antibodies for transglutaminase 2 are ≥10× ULN, endomysial antibodies are positive in a second blood sample and the patient/family agrees with the no-biopsy approach. • Literature on the effect of the no-biopsy approach on dietary adherence and HRQOL is scarce. WHAT IS NEW: • Omitting duodenal biopsies does not influence dietary adherence and quality of life. • In our cohort, lower quality of life measured with the CDDUX subscale 'Having CD' is more likely to be related to shorter disease duration than to the diagnostic approach.

UK NEQAS and BSHI guideline: Laboratory testing and clinical interpretation of HLA genotyping results supporting the diagnosis of coeliac disease.

Coeliac disease is a common immune-mediated inflammatory disorder caused by dietary gluten in genetically susceptible individuals. While the diagnosis of coeliac disease is based on serological and histological criteria, HLA-DQ genotyping can be useful, especially in excluding the diagnosis in patients who do not carry the relevant DQ heterodimers: DQA1*05 DQB1*02, DQB1*03:02 or DQA1*02 DQB1*02 (commonly referred to as DQ2.5, DQ8 and DQ2.2, respectively). External quality assessment results for HLA genotyping in coeliac disease have revealed concerning errors in HLA genotyping, reporting and clinical interpretation. In response, these guidelines have been developed as an evidence-based approach to guide laboratories undertaking HLA genotyping for coeliac disease and provide recommendations for reports to standardise and improve the communication of results.

Examination of the relationship between ABO/Rh blood groups and dietary compliance in children with coeliac disease: A single-centre experience.

AIM: Coeliac disease (CD) is an autoimmune enteropathy that develops upon ingestion of food containing gluten. The established link between ABO blood groups and numerous infectious and non-infectious illnesses prompted this investigation into blood group distribution and its relationship with dietary compliance among children diagnosed with CD. METHODS: In this retrospective study, patients with CD who were followed for ≥1 year at the paediatric gastroenterology outpatient clinic of our hospital were evaluated. History, physical examination and coeliac serology results were reviewed for each patient. Patients were divided into two groups based on self-reported compliance to a gluten-free diet: diet-adherent and non-diet-adherent. Patient and control groups were examined in terms of ABO blood groups. RESULTS: A total of 177 patients with CD were included in the study. A control group of 211 age- and sex-matched children without any chronic disease who had undergone blood group testing for various reasons was included for comparison. A total of 65% (n = 115) of the patients were girls, and 35% (n = 62) were boys. No significant relationship was found between CD diagnosis and ABO blood groups among patients (P = 0.559). Furthermore, the dietary compliance status of the patients was not associated with any specific blood group (P = 0.951). CONCLUSION: No notable difference was found between patients with CD with or without gluten-free diet compliance in terms of the distribution of ABO blood groups and Rhesus (Rh) factor. Therefore, it can be inferred that all blood groups and subgroups carry an equal risk for CD.

The financial impact on people with coeliac disease of withdrawing gluten-free food from prescriptions in England: findings from a cross-sectional survey.

BACKGROUND: A lifelong gluten-free diet is the only treatment for coeliac disease. The cost and availability of gluten-free substitute food (GFSF) remain challenging. Some local areas in England have stopped gluten-free prescriptions for coeliac disease. The aim of this paper is to present the quantitative findings of the financial impact of prescription withdrawal on people with coeliac disease. METHODS: A cross-sectional survey with adults in England who reported having been diagnosed with coeliac disease by a health professional. The postal survey was distributed by Coeliac UK to their members in 13 prescribing and 13 non-prescribing local areas that were matched for geographical location and level of deprivation. Additionally, an advertisement for the survey was placed on social media. The questionnaire contained items on the availability and use of prescriptions; the weekly amount spent on GFSF; amount of specific GFSF bought; affordability of GFSF; demographics and health-related variables. Data were analysed by descriptive statistics, analysis of variance and regression analysis. RESULTS: Of the 1697 participants, 809 resided in areas that provided prescriptions and 888 in non-prescribing areas. Participants self-report of their prescription did not always match the local area prescription policy. There was no statistically significant difference between prescribing and non-prescribing areas in how easy or difficult participants found it to obtain GFSF (p = 0.644) and its availability in various locations. Participants in non-prescribing areas purchased most types of GFSF items in statistically significantly higher quantities and thereby spent an additional £11.32/month on GFSF items than participants in prescribing areas (p < 0.001). While taking into account the self-reported prescription status, the amount increased to £14.09/month (p < 0.001). Although affordability to buy GFSF did not differ based on local area prescription policy or self-reported prescription status, it was dependent on equivalised annual income. However, affordability did not influence spending on GFSF. Regression analysis indicated that males and households with additional members with coeliac disease spent more on GFSF. CONCLUSIONS: The study has highlighted that gluten-free prescription withdrawal can have financial implications for people with coeliac disease. Any future changes to the prescription policy of GFSF should consider the impact on the population, especially lower income households.

The affordability and obtainability of gluten-free foods for adults with coeliac disease following their withdrawal on prescription in England: A qualitative study.

BACKGROUND: Changes to prescribing policies in England have restricted or stopped access to gluten-free food on prescription for people with coeliac disease in some geographical areas. The present study aimed to explore the impact of these changes on the affordability and obtainability of gluten-free foods for adults with coeliac disease. METHODS: Semi-structured qualitative interviews (n = 24) were conducted with people with coeliac disease living in areas where prescriptions for gluten-free foods were no longer available, were restricted or followed national guidelines. Interviews explored the impact of gluten-free prescribing changes on the affordability and obtainability of gluten-free food, as well as dietary adherence. RESULTS: All participants considered gluten-free substitute foods to be expensive. Participants felt the availability of gluten-free foods has improved over time, also acknowledging some challenges remain, such as limited local availability. For most, the withdrawal of prescriptions had minimal impact requiring small adjustments such as reducing the quantity of foods obtained. However, greater challenges were faced by those less mobile, permanently sick or disabled and/or on lower incomes. CONCLUSIONS: The majority of participants affected by the withdrawal of prescriptions were able to adapt to cope with these changes. However, participants with mobility issues, who are permanently sick or disabled and/or on lower incomes were struggling to afford and obtain gluten-free substitute foods from elsewhere. The withdrawal of prescriptions may further widen health inequalities. Further research should focus on the long-term impacts of prescription withdrawal for the vulnerable groups identified.