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1.
BMJ Open ; 14(10): e084365, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39384235

RESUMO

INTRODUCTION: Coeliac disease (CD) affects 1% of the population worldwide. The only available evidence-based treatment is a strict gluten-free diet (GFD), which can readily lead to weight gain and unfavourable metabolic changes (eg, dyslipidaemia, fatty liver disease and insulin resistance) if followed without adequate dietary control. That can lead to increased cardiovascular risk (CV). We planned a randomised controlled trial to test the effect of a group-based, structured, 1-year, advanced dietary education, per the proposal of a Mediterranean diet vs standard of care, regarding the most relevant CV risk factors (eg, metabolic parameters and body composition) in CD patients. METHODS AND ANALYSIS: Randomisation will occur after the baseline dietary education and interview in a 1:1 allocation ratio. Outcomes include anthropometric parameters (body composition analysis including weight, Body Mass Index, fat mass, per cent body fat, skeletal muscle mass, visceral fat area and total body water) and CV risk-related metabolic parameters (eg, lipid profile, homocysteine, fasting glucose, haemoglobin A1c, Homeostatic Model Assessment Index, metabolic hormones, waist circumference, blood pressure, liver function tests, liver steatosis rate and diet composition). In this study, we aim to draw attention to a new aspect regarding managing CD: dietary education can lead to a better quality of the GFD, thereby reducing the risk of potential metabolic and CV complications. ETHICS AND DISSEMINATION: The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (27521-5/2022/EÜIG). Findings will be disseminated at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05530070.


Assuntos
Composição Corporal , Doenças Cardiovasculares , Doença Celíaca , Fatores de Risco de Doenças Cardíacas , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Doença Celíaca/dietoterapia , Doença Celíaca/complicações , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/etiologia , Dieta Mediterrânea , Estudos Multicêntricos como Assunto , Dieta Livre de Glúten , Masculino
2.
Histopathology ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39375308

RESUMO

AIMS: Diagnosis of coeliac disease (CD) with mild mucosal changes is difficult for all parties involved. We aimed to determine the power of T cell receptor (TCR)γδ+ intra-epithelial lymphocytes (IELs) in discriminating CD from other causes of intra-epithelial lymphocytosis using a new monoclonal antibody. METHODS: A total of 167 cases categorised as coeliac (117 untreated CD, classified according to Marsh, updated by Ensari, including 29 type 1, 29 type 2, 39 type 3 and 20 treated CD), and non-coeliac groups (24 controls and 26 non-coeliac IELosis) based on clinical, serological and histological data were studied for IEL counts enumerated per 100 enterocytes using haematoxylin and eosin, CD3, TCR δ-stains. RESULTS: TCRγδ+ IELs were significantly higher in CD (24.83 ± 16.13) compared to non-CD (6.72 ± 6.32) and were correlated with the degree of mucosal damage. Both γδ+ IEL count and ratio showed higher performance in differentiating untreated coeliacs from controls, with a sensitivity of 83.76; 85.57 and specificity of 95.83; 79.17, respectively. TCRγδ+ IEL counts distinguished type 1 CD (20.41 ± 13.57) from non-coeliac IELosis (9.42 ± 7.28) (p = 0.025). Discriminant analysis revealed that villus/crypt ratio, γδ+ and CD3+ IEL counts, γδ+/CD3+IEL ratio, IEL distribution pattern were potent discriminants and correctly classified 82.3% of cases while the algorithm accurately diagnosed 93.4% of cases. CONCLUSIONS: The new antibody detecting γδ+ IELs in FFPE sections revealed thresholds of 10.5 for γδ+ IELs and 14% for γδ+/CD3+IEL ratio which distinguished coeliacs from non-coeliacs with high sensitivity and specificity, particularly in cases with normal villus/crypt axis including type 1 CD, non-CD IELosis and controls. A 'coeliac algorithm' based on γδ+ IELs is proposed with the hope that it will be used in the histopathological diagnostic approach by the pathology community.

3.
Dig Liver Dis ; 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39370353

RESUMO

BACKGROUND: Fecal calprotectin (FC) is a non-invasive biomarker of gut inflammation, but its role in celiac disease (CD) and non-celiac enteropathies (NCEs) is undefined. AIMS: To retrospectively evaluate FC in patients with CD and NCEs as a tool for assessing disease activity and predicting long-term outcomes. METHODS: Patients with uncomplicated and complicated CD, and NCEs with data on FC, evaluated at our center between June-2008 and December-2023, were enrolled. The relationship between elevated FC (>50 mg/kg) and disease activity was statistically analysed and Cox regression adjusted for age and sex was used to compare development of complications and mortality in patients with elevated and normal FC. RESULTS: 177 patients (109F, mean age at diagnosis 39±20 years, 132 CD, 17 complicated CD, 28 NCEs) were enrolled. 55 patients had elevated FC, which was associated with lack of clinical and histological response to therapy (both p < 0.001). During a median follow-up of 103 months (IQR 54-176), 22 patients developed complications (15.4 %) and 21 died (11.9 %). Elevated FC was significantly more common in complicated CD (70.6 %) and NCEs (67.9 %) than in uncomplicated CD (18.2 %), p < 0.001. Elevated FC was independently predictive of developing complications (HR 4.8,95 %CI 1.4-17.7, p = 0.01) and mortality (HR 4.8,95 %CI 1.6-14.3, p < 0.01). CONCLUSION: FC is a promising non-invasive biomarker for assessing disease severity and long-term outcomes in CD and NCEs.

4.
Br J Hosp Med (Lond) ; 85(9): 1-21, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39347683

RESUMO

Coeliac disease is a common autoimmune disorder that affects nearly 1% of the general population. Current diagnostic strategies involve active case finding, serological tests, and endoscopy with biopsies. However, many patients with coeliac disease remain undiagnosed due to a wide gap between clinical guidelines and real-world practice in the diagnosis of adult coeliac disease. This highlights the need for increased education, training, and targeted quality-improvement interventions to optimise the diagnosis of coeliac disease.


Assuntos
Doença Celíaca , Doença Celíaca/diagnóstico , Humanos , Adulto , Guias de Prática Clínica como Assunto , Biópsia/métodos , Testes Sorológicos/métodos
5.
Front Genet ; 15: 1441769, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39315311

RESUMO

Coeliac disease (CD) is an autoimmune disorder caused by the ingestion of gluten-containing grains. One of the prerequisites for the development of the disease is the presence of specific combinations of HLA alleles at the DQA1 and DQB1 loci. The HLA test is a supportive diagnostic test. In the Czech Republic, approximately 3,500 HLA tests for CD diagnosis are performed annually in almost three dozen laboratories. The HLA Department of the Institute of Haematology and Blood Transfusion in Prague has been offering the EPT "Detection of HLA Alleles Associated with Diseases" for more than 10 years. The results are evaluated in terms of the correct determination of predisposing alleles/allelic groups and clinical interpretation. Every year, we notice some problems with the detection of CD-associated alleles and the interpretation of results. Annual workshops are part of this EPT, and they also include recommendations for the interpretation of results. This interpretation is evolving based on the current knowledge in the field. The current recommendation for interpretation was adopted in 2023, dividing HLA-DQA1/DQB1 genotypes into three categories: 1) detected HLA genotype is associated with predisposition to coeliac disease; 2) coeliac disease could not be excluded based on the detected HLA genotype; 3) coeliac disease could be excluded with high probability based on the detected HLA genotype. The quality of examination is increasing but still needs improvement. Correct results and accurate interpretation can inform clinicians' decisions about the diagnosis of coeliac disease in appropriate patients.

6.
J Clin Med ; 13(18)2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39336903

RESUMO

Background: There is a paucity of data on mesenteric lymph node cavitation syndrome (MLNCS), a rare condition associated with coeliac disease (CD), characterized by central necrosis within enlarged mesenteric lymph nodes. The largest case series of MLNCS was completed in 1984, (n = 6) and a poor prognosis was identified. Methods: A case series of all patients was conducted with MLNCS treated at the UK NHS England National Centre for Refractory Coeliac Disease between 2000 and 2023. A further literature review was conducted using PubMed and Google Scholar for patients with MLNCS and coeliac disease until 2023. Results: In total, there were 51 patients (6 from our case series and 45 from the literature review); 57% were female, and the mean age was 52.8 years (SD: 14.01 years). The most common presenting symptoms were weight loss (80%) and diarrhea (65%), and patients often had hyposplenism (80%). Persistent villous atrophy was present in 88% of the patients. Ten patients also had Refractory Coeliac Disease. Most of the patients (90%) were on a GFD, but the effect of this is unclear. Treatment with steroids and immunosuppressants resulted in a 40% survival rate. The overall mortality was 43%, associated with cachexia, sepsis, infectious complications, and lymphoma. Conclusions: MLNCS has a poor prognosis, and its diagnosis should prompt further intervention and careful follow-up. Patients commonly present with weight loss and hyposplenism should prompt further investigation. Current treatment options are inadequate and novel therapies are required.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39300689

RESUMO

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.

9.
J Clin Med ; 13(17)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39274362

RESUMO

Background/Objectives: Constrictive pericarditis very rarely causes protein-losing enteropathy (PLE) induced by secondary intestinal lymphangiectasia. This study thoroughly reviewed the literature to shed light on the clinical management of PLE provoked by intestinal lymphangiectasia following constrictive pericarditis. Methods: We performed a PubMed search using the keywords enteropathy, protein-losing enteropathy, pericarditis, acute pericarditis, pericardial effusion, recurrent pericarditis, constrictive pericarditis, noninfectious pericarditis, idiopathic pericarditis, and infective pericarditis, with only English-language publications included. Results: Although constrictive pericarditis is primarily idiopathic, less common causes include infectious etiologies, connective/autoimmune tissue disorders, previous cardiac surgery, congenital syndromes, and cancer. On the one hand, PLE secondary to intestinal lymphangiectasia may cause a severe cellular immune deficiency that could raise infection hazards due to lymphocytopenia and hypogammaglobulinemia. On the other hand, lymphocytopenia may cause anergy and mask an underlying tuberculous etiology of constrictive pericarditis. Cardiac catheterization is the most useful diagnostic tool for constrictive pericarditis, though it may be misdiagnosed in rare cases. The videocapsule endoscopy and double-balloon enteroscopy techniques can detect small bowel lymphangiectasias distal to the Treitz ligament. MRI or a CT scan helps confirm constrictive pericarditis, visualize lymphangiectasias, and reveal features specific to the underlying etiology of PLE. Radioisotopic techniques may ensure PLE diagnosis in challenging cases, whereas fecal alpha1-antitrypsin can estimate gastrointestinal protein loss. Conclusions: Constrictive pericarditis is rarely associated with PLE. The cardio-intestinal abnormalities of PLE caused by constrictive pericarditis are frequently reversed following a complete pericardiectomy, though its ability to invert severe hypoalbuminemia is currently unknown.

10.
Food Chem Toxicol ; 193: 115019, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39307344

RESUMO

Recent reports have highlighted that beer labelled "gluten-free", crafted with enzymatic treatments to remove gluten, may contain polypeptides that could be immunotoxic to individuals with coeliac disease. As strict adherence to a gluten-free diet is the only way to manage this condition, accurate labelling is crucial to those with coeliac disease. This paper aims to discuss the presence, levels and immunogenicity of gluten peptides found in gluten-reduced barley beers. While advances have been made in the detection and quantification of gluten peptides in beer, there are still challenges to the interpretation of gluten measurements as well as to assess whether peptides are immunotoxic in vivo. To make progress, future efforts should involve a combination of in vivo toxicity assessment of the degraded proteins, development of standardised gluten-free production strategies to minimise variability in gluten fragment presence, guidance on how to control the outcome as well as to develop appropriate reference materials and calibrators.

11.
Int J Food Sci Nutr ; 75(7): 664-672, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39252429

RESUMO

Nutritional value of the Gluten-free products (GFPs) has been highly debated. Aiming to assess the nutritional value of the cereal-based GFPs in the Greek market, information from the nutritional label and the ingredients list, of all GFPs and their gluten-containing (GC) counterparts available in a supermarket offering the greatest availability in the capital of Greece, were recorded. The sample consisted of 913 products: 351 GFPs and 562 GCPs, classified into 12 categories (e.g., breads, melbas, breakfast cereals, cereal bars, pasta, flours, cookies). With minor exceptions, comparisons among all food categories regarding nutrient profile and nutritional claims showed mixed results, though supporting an overly comparable nutritional profile of the GFPs. Still, a quarter of all GFPs presented an unhealthy nutritional profile. The findings of the present study are highly in agreement with those of relevant studies in the literature, that do not support an inferior nutritional profile compared to GC counterparts.


Assuntos
Dieta Livre de Glúten , Grão Comestível , Rotulagem de Alimentos , Glutens , Valor Nutritivo , Grécia , Grão Comestível/química , Glutens/análise , Humanos , Supermercados
12.
Eur J Health Econ ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39212881

RESUMO

OBJECTIVES: Multiple studies suggest that the EQ-5D may overestimate health-related quality of life (HRQoL) in patients with coeliac disease (CD). We aimed to develop and psychometrically test potentially relevant bolt-on dimensions to improve the measurement performance of the EQ-5D-5L in CD patients. METHODS: The development and selection of bolt-ons were informed by a literature review on HRQoL in CD, expert and patient input. A cross-sectional online survey was conducted amongst 312 adult CD patients. Respondents completed the EQ-5D-5L, two condition-specific bolt-ons newly-developed for the present study [dining (DI) and gastrointestinal problems (GI)] and three existing bolt-ons [cognition (CO), sleep (SL) and tiredness (TI)]. The following psychometric properties were tested: ceiling, informativity, convergent and known-group validity, and dimensionality (confirmatory factor analysis). RESULTS: Adding the TI, SL, GI, DI and CO individual bolt-ons reduced the ceiling of the EQ-5D-5L (39%) to 17%, 23%, 24%, 26% and 37%, respectively. GI excelled with strong convergent validity with the Gastrointestinal Symptom Rating Scale total score (rs=0.71) and improved the discriminatory power for all known-groups. GI was the only bolt-on loading on a different factor from the five core dimensions, whereas the other four bolt-ons loaded onto the same 'psychosocial health' factor as the EQ-5D-5L anxiety/depression dimension. CONCLUSION: The DI, GI, SL and TI bolt-ons, especially the GI, enhance the validity of EQ-5D-5L in patients with CD, suggesting their value in capturing important HRQoL aspects potentially missed by the five core dimensions. These bolt-ons can be used in sensitivity analyses supporting health technology assessments and subsequent resource allocation decisions.

13.
Artigo em Inglês | MEDLINE | ID: mdl-39192618

RESUMO

BACKGROUND: There is potential for a paradigm shift from a biopsy-to a serology-based diagnosis of coeliac disease in selected adult patients. However, it remains unknown if this approach would be acceptable to patients. We aimed to explore patients' preferences regarding the no-biopsy approach for coeliac disease diagnosis. METHODS: We developed a discrete choice experiment survey containing 12 different scenarios with two possible alternatives (endoscopy & biopsy or serology) to estimate patient preferences. The scenarios were based on 5 attributes: risk of false positive results, risk of missed diagnosis, waiting time to start treatment, risk of complications, discomfort, or pain. Patient preferences and the relative importance of the attributes were estimated using a mixed logit model. RESULTS: In total, 385 people (70.6% female, 98.2% white) across the four nations of the United Kingdom completed the survey. Respondents preferred a serology-based diagnosis over endoscopy and duodenal biopsies (59% vs. 41%, ß coefficient 1.54, p < 0.001). Diagnostic test accuracy (p < 0.001), shorter waiting time to start treatment (p < 0.001), and discomfort levels during the procedure (p < 0.001) were the most important attributes to respondents. The risk of complications, including perforation and bleeding, did not significantly influence respondents' choices. Respondents with previous endoscopy experience were more willing to undergo endoscopy compared with those who never had one. CONCLUSION: The no-biopsy approach to diagnosing coeliac disease is acceptable and preferred by patients over endoscopy and biopsy. Our findings highlight the importance of patient-centred care and shared decision-making in guiding diagnostic strategies for optimal patient outcomes.

14.
Scand J Gastroenterol ; 59(9): 1049-1054, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39126366

RESUMO

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.


Assuntos
Absorciometria de Fóton , Doença Celíaca , Osteoporose , Fraturas por Osteoporose , Humanos , Doença Celíaca/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Estudos Retrospectivos , Adulto , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/diagnóstico , Osteoporose/complicações , Osteoporose/epidemiologia , Biópsia , Fatores de Risco , Idoso , Prevalência , Modelos Logísticos , Sensibilidade e Especificidade , Incidência , Densidade Óssea , Doenças Ósseas Metabólicas/epidemiologia , Doenças Ósseas Metabólicas/diagnóstico , Proteínas de Ligação ao GTP , Valor Preditivo dos Testes
15.
Nutrients ; 16(16)2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39203732

RESUMO

BACKGROUND: Data on resilience, the ability to recover from adversity, in coeliac disease (CeD) are lacking. AIM: To assess the degree of resilience in patients with CeD on a gluten-free diet (GFD), and its association with clinical features, sociodemographic factors, psychological morbidity, and quality of life (QOL). METHODS: A cross-sectional multicentre Italian study was conducted on adult CeD patients between May 2022 and April 2023. Connor-Davidson Resilience Scale (CD-RISC), the Coeliac Disease-specific Quality of Life Scale (CD-QOL), the State-Trait Anxiety Inventory scale (STAI-Y), and the Beck Depression Inventory scale (BDI) were used to evaluate resilience, QOL, anxiety, and depression, respectively. A multivariate analysis was conducted to identify factors independently associated with the degree of resilience. RESULTS: A total of 305 patients (221 F, mean age at CeD diagnosis 36 ± 16 years) on a long-term GFD (median 8 years, IQR 3-17) were enrolled. A total of 298/305 patients (98%) had a high level of resilience (CD-RISC ≥ 35). At univariate analysis, resilience was statistically associated with male gender (p = 0.03), age at enrolment (p = 0.02), marital status (p = 0.03), QOL (p < 0.001), anxiety (p < 0.001), and depression (p < 0.001). On multivariate regression analysis, trait anxiety (STAI-Y2, p < 0.001) and depression (BDI, p = 0.02) were independent predictors of lower levels of resilience. CONCLUSIONS: Higher trait anxiety predicts lower levels of resilience. Targeted interventions in this subgroup of patients may be helpful for their management and follow-up.


Assuntos
Ansiedade , Doença Celíaca , Depressão , Dieta Livre de Glúten , Qualidade de Vida , Resiliência Psicológica , Humanos , Dieta Livre de Glúten/psicologia , Masculino , Feminino , Estudos Transversais , Doença Celíaca/dietoterapia , Doença Celíaca/psicologia , Adulto , Itália , Pessoa de Meia-Idade , Ansiedade/psicologia , Depressão/psicologia , Adulto Jovem
16.
Front Psychiatry ; 15: 1312117, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39100855

RESUMO

Background: To explore the potential causal associations between coeliac disease(CD) and postpartum depression(PPD) by using two-sample Mendelian randomization(MR) analysis. Methods: The IEU OPEN GWAS project was utilized to identify genetic loci strongly associated with CD as instrumental variables (IVs), and MR analysis was performed using inverse variance weighting(IVW), weighted median, weighted model, and MR-Egger. MR analyses were used to examine whether there was a link between CD and PPD, with an OR and 95% CI. Meanwhile, the relationship between CD and depression(DP) was analyzed using MR. The sensitivity analysis was conducted using MR-Egger intercept analysis, Cochran's Q test, and leave-one-out analysis. Results: From the GWAS online database, 13 single-nucleotide polymorphisms (SNPs) were chosen as IVs. The IVW results showed a relationship between PPD and a genetically predicted risk of developing CD (OR = 1.022, 95% CI: 1.001-1.044, P = 0.043). However, the presence of DP was not linked with CD (OR=0.991, 95% CI: 0.978-1.003, P=0.151). Potential horizontal pleiotropy was not discovered using MR-Egger intercept analysis (PPD: P=0.725; DP: P=0.785), and Cochran's Q test for heterogeneity revealed no significant heterogeneity (PPD: P=0.486; DP: P=0.909). A leave-one-out analysis found that individual SNPs had minimal effect on overall causal estimations. Conclusion: MR research discovered a link between CD and PPD.

17.
Cytokine ; 182: 156722, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39116536

RESUMO

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.


Assuntos
Gliadina , Antígenos HLA-DQ , Camundongos Transgênicos , Triticum , Animais , Gliadina/imunologia , Antígenos HLA-DQ/imunologia , Camundongos , Triticum/imunologia , Feminino , Citocinas/metabolismo , Baço/imunologia , Doença Celíaca/imunologia , Humanos , Toxina da Cólera/farmacologia , Toxina da Cólera/imunologia , Toxina da Cólera/administração & dosagem , Interferon gama/metabolismo , Intestinos/imunologia , Linfonodos/imunologia , Linfonodos/efeitos dos fármacos , Imunização/métodos , Glutens/imunologia , Glutens/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-17/metabolismo
18.
Front Nutr ; 11: 1395801, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39166131

RESUMO

Background and objectives: Lactose intolerance and coeliac disease are common clinical nutrient malabsorption disorders, with an unclear pathogenesis and limited therapeutic options. It is widely believed that the gut microbiota plays an important role in many digestive disorders, but its role in lactose intolerance and coeliac disease is not yet clear. This study aimed to investigate the correlation between gut microbiota and lactose intolerance and coeliac disease. Materials and methods: This study utilized the genome-wide association study database to investigate the association between gut microbiota and lactose intolerance and coeliac disease using Mendelian randomization (MR). The robustness of our findings was confirmed through subsequent analyses including Cochrane's Q statistic, MR-Egger Intercept Regression, MR-PRESSO Global Test and Leave-one-out methods. Results: By employing the inverse variance weighted method, we identified that family Veillonellaceae, genus Oxalobacter and Senegalimassilia were protective against lactose intolerance, whereas genus Anaerotruncus, Eubacterium rectale group and Ruminococcus2 were found to be risk factors for lactose intolerance. Regarding coeliac disease, class Bacilli and Gammaproteobacteria, family FamilyXIII and Veillonellaceae, genus Eisenbergiella, Lachnoclostridium, RuminococcaceaeUCG014 and Ruminococcus2 were identified as protective factors, while class Betaproteobacteria, genus Eubacterium xylanophilum group and Blautia were risk factors. Furthermore, reverse the MR analysis did not reveal any evidence of a causal relationship between lactose intolerance or coeliac disease and the bacteria identified in our study. Conclusion: This study provides novel insights into exploring the role of gut microbiota in lactose intolerance and coeliac disease; however, further experiments investigations are required to elucidate the specific underlying mechanisms.

19.
Artigo em Inglês | MEDLINE | ID: mdl-39091660

RESUMO

Background and Objective: Coeliac disease (CD) is a common autoimmune disorder triggered by gluten consumption in genetically predisposed individuals. CD is characterised by chronic inflammation in the small bowel mucosa with an influx of lymphocytes, followed by crypt hyperplasia and villous atrophy. The gold standard test to diagnose CD is endoscopy with duodenal biopsies. However, variations in practice between endoscopists can lead to missed diagnoses. This review aims to discuss the role of endoscopy in the diagnosis of CD, highlighting the performance measures of endoscopy in CD and the advancement in endoscopic techniques for the optical diagnosis of villous atrophy. Methods: We searched PubMed and Google Scholar from their inception to December 2023 for relevant articles on the role of endoscopy in CD. Two authors reviewed these references, and relevant studies were included in the discussion section of this review. Key Content and Findings: We provide an up-to-date assessment of the diagnostic accuracy of endoscopic markers of CD and the performance of enhanced endoscopic imaging to identify villous atrophy during endoscopy. We propose a set of benchmarks for endoscopy in CD and discuss the potential role of artificial intelligence (AI) in the endoscopic diagnosis of CD. Conclusions: Performing high-quality endoscopy and identifying strategies to reduce inter-endoscopist variations may reduce missed diagnoses. Adopting advanced endoscopic techniques and embracing new technologies such as AI could enhance diagnostic accuracy and improve patient care.

20.
Gut ; 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39153845

RESUMO

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.

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