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1.
World J Gastroenterol ; 30(11): 1545-1555, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38617446

RESUMO

BACKGROUND: The gluten-free diet (GFD) has limitations, and there is intense research in the development of adjuvant therapies. AIM: To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease (AN-PEP) on inadvertent gluten exposure and symptom prevention in adult celiac disease (CeD) patients following their usual GFD. METHODS: This was an exploratory, double-blind, randomized, placebo-controlled trial that enrolled CeD patients on a long-term GFD. After a 4-wk run-in period, patients were randomized to 4 wk of two AN-PEP capsules (GliadinX; AVI Research, LLC, United States) at each of three meals per day or placebo. Outcome endpoints were: (1) Average weekly stool gluten immunogenic peptides (GIP) between the run-in and end of treatments and between AN-PEP and placebo; (2) celiac symptom index (CSI); (3) CeD-specific serology; and (4) quality of life. Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments. RESULTS: Forty patients were randomized for the intention-to-treat analysis, and three were excluded from the per-protocol assessment. Overall, 628/640 (98.1%) stool samples were collected. GIP was undetectable (< 0.08 µg/g) in 65.6% of samples, and no differences between treatment arms were detected. Only 0.5% of samples had GIP concentrations sufficiently high (> 0.32 µg/g) to potentially cause mucosal damage. Median GIP concentration in the AN-PEP arm was 44.7% lower than in the run-in period. One-third of patients exhibiting GIP > 0.08 µg/g during run-in had lower or undetectable GIP after AN-PEP treatment. Compared with the run- in period, the proportion of symptomatic patients (CSI > 38) in the AN-PEP arm was significantly lower (P < 0.03). AN-PEP did not result in changes in specific serologies. CONCLUSION: This exploratory study conducted in a real-life setting revealed high adherence to the GFD. The AN-PEP treatment did not significantly reduce the overall GIP stool concentration. However, given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm, further clinical research is warranted.


Assuntos
Aspergillus niger , Aspergillus , Doença Celíaca , Adulto , Humanos , Doença Celíaca/diagnóstico , Dieta Livre de Glúten , Glutens , Prolil Oligopeptidases , Qualidade de Vida
2.
Nutrients ; 15(23)2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38068784

RESUMO

A large number of patients with celiac disease (CD) remain undiagnosed because they do not fulfill the criteria for entry into the conventional diagnostic workflow. This study evaluated the clinical utility of anti-tissue transglutaminase IgA antibody lateral flow immunoassays (anti-tTG-IgA LFIA) in the undiagnosed-CD-based pediatric population and the impact of a gluten-free diet (GFD) on screening-detected CD. A total of 576 volunteers were tested for anti-tTG-IgA. Gluten consumption habits, CD related symptoms, and risk factors for CD development were evaluated. Volunteers testing positive for anti-tTG-IgA were referred to the conventional CD diagnostic workflow, and the impact of the GFD on health-related quality of life (HR-QoL) was measured. Among them, 13 had a positive anti-tTG-IgA LFIA test result: 11 had confirmed CD (1.91%), one refused confirmatory tests, and another is undergoing diagnosis. Regarding the CD prevalence, no significant differences were observed among risk (1.89%) and symptomatic (2.65%) groups and the entire tested population (1.55%). Rapid anti-tTG-IgA LFIAs could be of clinical utility in primary care for the early identification of children with CD unidentified by the conventional diagnostic workflow. It could potentially reduce the costs of undiagnosed CD, avoiding unnecessary referrals to gastroenterologists, reducing diagnosis delays and long-term problems, and improving patients' HR-QoL.


Assuntos
Doença Celíaca , Humanos , Criança , Doença Celíaca/diagnóstico , Qualidade de Vida , Transglutaminases , Diagnóstico Precoce , Imunoglobulina A , Autoanticorpos
3.
Nutrients ; 15(7)2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37049570

RESUMO

A gluten-free diet (GFD) is currently the only treatment available for patients with celiac disease (CD). However, adherence to a GFD can be challenging because gluten is present in many foods. A lifelong follow-up of patients with CD must be performed to promote adherence to a GFD and to identify the appearance of symptoms and the associated diseases. Therefore, the development of tools to analyze gluten exposure in these patients is important. This study proposes the development of the first automatable ELISA to monitor adherence to a GFD through the quantification of urine gluten immunogenic peptides (u-GIP). Seven healthy volunteers without suspicion of CD and 23 patients with CD were monitored as part of this study to optimize, validate, and apply this assay. Non-interference was found in the urine matrix, and the recovery percentage for spiked samples was 81-101%. The u-GIP was stable for up to 16 days when the samples were stored at different temperatures. Overall, 100% of the patients had detectable u-GIP at diagnosis (range of 0.39-2.14 ng GIP/mL), which reduced to 27% after 12 months on a GFD. Therefore, this highly sensitive immunoassay would allow the analysis of u-GIP from a large battery of samples in clinical laboratories of specialized healthcare centers.


Assuntos
Doença Celíaca , Glutens , Humanos , Glutens/análise , Dieta Livre de Glúten , Imunoensaio , Peptídeos/urina , Cooperação do Paciente
4.
Aliment Pharmacol Ther ; 57(9): 993-1003, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36890679

RESUMO

BACKGROUND: Gluten-free diet (GFD) is the only treatment for patients with coeliac disease (CD) and its compliance should be monitored to avoid cumulative damage. AIMS: To analyse gluten exposures of coeliac patients on GFD for at least 24 months using different monitoring tools and its impact on duodenal histology at 12-month follow-up and evaluate the interval of determination of urinary gluten immunogenic peptides (u-GIP) for the monitoring of GFD adherence. METHODS: Ninety-four patients with CD on a GFD for at least 24 months were prospectively included. Symptoms, serology, CDAT questionnaire, and u-GIP (three samples/visit) were analysed at inclusion, 3, 6, and 12 months. Duodenal biopsy was performed at inclusion and 12 months. RESULTS: At inclusion, 25.8% presented duodenal mucosal damage; at 12 months, this percentage reduced by half. This histological improvement was indicated by a reduction in u-GIP but did not correlate with the remaining tools. The determination of u-GIP detected a higher number of transgressions than serology, regardless of histological evolution type. The presence of >4 u-GIP-positive samples out of 12 collected during 12 months predicted histological lesion with a specificity of 93%. Most patients (94%) with negative u-GIP in ≥2 follow-up visits showed the absence of histological lesions (p < 0.05). CONCLUSION: This study suggests that the frequency of recurrent gluten exposures, according to serial determination of u-GIP, could be related to the persistence of villous atrophy and that a more regular follow-up every 6 months, instead of annually, provides more useful data about the adequate adherence to GFD and mucosal healing.


Assuntos
Doença Celíaca , Glutens , Humanos , Glutens/efeitos adversos , Glutens/análise , Seguimentos , Dieta Livre de Glúten , Peptídeos , Cooperação do Paciente
6.
Foods ; 12(1)2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36613374

RESUMO

Most gluten analysis methods have been developed to detect intact gluten, but they have shown limitations in certain foods and beverages in which gluten proteins are hydrolyzed. Methods based on G12/A1 moAbs detect the sequences of gluten immunogenic peptides (GIP), which are the main contributors to the immune response of celiac disease (CD). Immunogenic sequences with tandem epitopes for G12/A1 have been found in beers with <20 mg/kg gluten, which could be consumed by CD patients according to the Codex Alimentarius. Therefore, an accurate method for the estimation of the immunogenicity of a beer is to use two moAbs that can recognize celiac T cell epitopes comprising most of the immunogenic response. Here, a specific and sensitive method based on G12/A1 LFIA was developed to detect GIP in beers labeled gluten-free or with low gluten content, with an LOD of 0.5 mg/kg. A total of 107 beers were analyzed, of those 6.5% showed levels higher than 20 mg/kg gluten and 29% showed levels above the LOD. In addition, G12/A1 LFIA detected gluten in 15 more beer samples than competitive ELISA with another antibody. Despite their labeling, these beers contained GIP which may cause symptoms and/or intestinal damage in CD patients.

7.
Nutrients ; 13(12)2021 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-34960101

RESUMO

Celiac disease (CD) is a genetically predisposed, T cell-mediated and autoimmune-like disorder caused by dietary exposure to the storage proteins of wheat and related cereals. A gluten-free diet (GFD) is the only treatment available for CD. The celiac immune response mediated by CD4+ T-cells can be assessed with a short-term oral gluten challenge. This study aimed to determine whether the consumption of bread made using flour from a low-gluten RNAi wheat line (named E82) can activate the immune response in DQ2.5-positive patients with CD after a blind crossover challenge. The experimental protocol included assessing IFN-γ production by peripheral blood mononuclear cells (PBMCs), evaluating gastrointestinal symptoms, and measuring gluten immunogenic peptides (GIP) in stool samples. The response of PBMCs was not significant to gliadin and the 33-mer peptide after E82 bread consumption. In contrast, PBMCs reacted significantly to Standard bread. This lack of immune response is correlated with the fact that, after E82 bread consumption, stool samples from patients with CD showed very low levels of GIP, and the symptoms were comparable to those of the GFD. This pilot study provides evidence that bread from RNAi E82 flour does not elicit an immune response after a short-term oral challenge and could help manage GFD in patients with CD.


Assuntos
Pão , Doença Celíaca/imunologia , Dieta Livre de Glúten , Gliadina/genética , Gliadina/imunologia , Glutens/imunologia , Interferência de RNA , Triticum/genética , Triticum/imunologia , Adulto , Doença Celíaca/genética , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Interferência de RNA/imunologia , Triticum/química , Adulto Jovem
8.
Nutrients ; 13(7)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34210037

RESUMO

A gluten-free diet (GFD) is currently the only effective treatment for celiac disease (CD); an individual's daily intake of gluten should not exceed 10 mg. However, it is difficult to maintain a strict oral diet for life and at least one-third of patients with CD are exposed to gluten, despite their best efforts at dietary modifications. It has been demonstrated that both natural and certified gluten-free foods can be heavily contaminated with gluten well above the commonly accepted threshold of 20 mg/kg. Moreover, meals from food services such as restaurants, workplaces, and schools remain a significant risk for inadvertent gluten exposure. Other possible sources of gluten are non-certified oat products, numerous composite foods, medications, and cosmetics that unexpectedly contain "hidden" vital gluten, a proteinaceous by-product of wheat starch production. A number of immunochemical assays are commercially available worldwide to detect gluten. Each method has specific features, such as format, sample extraction buffers, extraction time and temperature, characteristics of the antibodies, recognition epitope, and the reference material used for calibration. Due to these differences and a lack of official reference material, the results of gluten quantitation may deviate systematically. In conclusion, incorrect gluten quantitation, improper product labeling, and poor consumer awareness, which results in the inadvertent intake of relatively high amounts of gluten, can be factors that compromise the health of patients with CD.


Assuntos
Doença Celíaca/dietoterapia , Dieta Livre de Glúten , Exposição Dietética/análise , Contaminação de Alimentos/análise , Glutens/análise , Exposição Dietética/prevenção & controle , Contaminação de Alimentos/prevenção & controle , Inocuidade dos Alimentos/métodos , Glutens/efeitos adversos , Humanos
9.
Nutrients ; 13(7)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201435

RESUMO

To date, the only treatment for celiac disease (CD) consists of a strict lifelong gluten-free diet (GFD), which has numerous limitations in patients with CD. For this reason, dietary transgressions are frequent, implying intestinal damage and possible long-term complications. There is an unquestionable need for non-dietary alternatives to avoid damage by involuntary contamination or voluntary dietary transgressions. In recent years, different therapies and treatments for CD have been developed and studied based on the degradation of gluten in the intestinal lumen, regulation of the immune response, modulation of intestinal permeability, and induction of immunological tolerance. In this review, therapeutic lines for CD are evaluated with special emphasis on phase III and II clinical trials, some of which have promising results.


Assuntos
Doença Celíaca/terapia , Doença Celíaca/imunologia , Doença Celíaca/microbiologia , Ensaios Clínicos como Assunto , Dieta Livre de Glúten , Microbioma Gastrointestinal , Glutens/efeitos adversos , Humanos , Imunomodulação
10.
Nutrients ; 13(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209138

RESUMO

Celiac disease (CD) is a chronic gluten-responsive immune mediated enteropathy and is treated with a gluten-free diet (GFD). However, a strict diet for life is not easy due to the ubiquitous nature of gluten. This review aims at examining available evidence on the degree of adherence to a GFD, the methods to assess it, and the barriers to its implementation. The methods for monitoring the adherence to a GFD are comprised of a dietary questionnaire, celiac serology, or clinical symptoms; however, none of these methods generate either a direct or an accurate measure of dietary adherence. A promising advancement is the development of tests that measure gluten immunogenic peptides in stools and urine. Causes of adherence/non-adherence to a GFD are numerous and multifactorial. Inadvertent dietary non-adherence is more frequent than intentional non-adherence. Cross-contamination of gluten-free products with gluten is a major cause of inadvertent non-adherence, while the limited availability, high costs, and poor quality of certified gluten-free products are responsible for intentionally breaking a GFD. Therefore, several studies in the last decade have indicated that many patients with CD who follow a GFD still have difficulty controlling their diet and, therefore, regularly consume enough gluten to trigger symptoms and damage the small intestine.


Assuntos
Doença Celíaca/dietoterapia , Dieta Livre de Glúten , Cooperação do Paciente , Doença Celíaca/epidemiologia , Seguimentos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Fatores de Risco
11.
Foods ; 10(3)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808639

RESUMO

One of the main concerns in gluten analysis is to achieve efficient extraction of gluten proteins. Conventional ethanol-based extraction solutions are inefficient and, because of this, it is necessary to use reducing agents or acids for proper solubilization. The extraction recommended by CODEX Standard 118-1979 (revised 2008) utilizes Cocktail solution (patent WO 02/092633 A1). However, it is harmful with a disgusting odor and is not compatible with some immunological techniques. Here, the versatility and extraction capacity of a new Universal Gluten Extraction Solution (UGES) (patent ES 2 392 412 A1) were evaluated using different methodological conditions, food matrices, and various immunological methods. UGES includes safer compounds for both the user and the environment, and it displayed similar extraction efficiency to that of the extraction method recommended for sandwich enzyme-linked immunosorbent assay (ELISA). The extraction time was significantly reduced from 100 to 40 min, depending on the type of the sample. Furthermore, unlike the currently used solution, UGES is compatible with competitive ELISA.

12.
Am J Gastroenterol ; 116(5): 1036-1043, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33491958

RESUMO

INTRODUCTION: A substantial proportion of adult patients with celiac disease on a gluten-free diet exhibit persistent villous atrophy, and inadvertent gluten exposure may be one of the causes. The aim of the present study was to evaluate villous atrophy persistence after 2 years on a gluten-free diet in de novo adult patients with celiac disease with strict control of gluten exposure. METHODS: Symptomatic de novo adult patients with celiac disease were prospectively included. Clinical visits and dietary surveillance were scheduled every 6 months during a 2-year follow-up period. At each visit, fecal samples were collected and stored at -20 °C until analysis for gluten immunogenic peptides (f-GIPs). A follow-up duodenal biopsy was performed at 2 years. We evaluated the variables associated with persistent villous atrophy. RESULTS: Seventy-six patients completed the study (36.5 ± 1.6 years, 73% women); persistent villous atrophy was observed in 40 (53%), whereas 72.5% were asymptomatic and 75% had negative serology. Detectable f-GIP >0.08 µg/g in at least 1 fecal sample was seen in 69% of patients. There were no significant differences in the median f-GIP at each visit and median area under the curve over the serial measurements between patients with persistent villous atrophy and those who recovered. On multivariate analysis, only older age was associated with persistent villous atrophy (32% for 16-30 years; 67% for >30 years; P = 0.016). DISCUSSION: The rate of persistent villous atrophy after 2 years was high in adult patients with celiac disease on an intentionally strict gluten-free diet. Low-level ongoing inadvertent gluten exposure could be a contributing factor to persistent villous atrophy.


Assuntos
Doença Celíaca/dietoterapia , Doença Celíaca/patologia , Dieta Livre de Glúten , Mucosa Intestinal/patologia , Microvilosidades/patologia , Adulto , Atrofia , Biópsia , Fezes/química , Feminino , Humanos , Masculino , Estudos Prospectivos , Espanha
13.
Aliment Pharmacol Ther ; 52(9): 1469-1479, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32981131

RESUMO

BACKGROUND: A major deficit in understanding and improving treatment in coeliac disease (CD) is the lack of empiric data on real world gluten exposure. AIMS: To estimate gluten exposure on a gluten-free diet (GFD) using immunoassays for gluten immunogenic peptides (GIP) and to examine relationships among GIP detection, symptoms and suspected gluten exposures METHODS: Adults with biopsy-confirmed CD on a GFD for 24 months were recruited from a population-based inception cohort. Participants kept a diary and collected urine samples for 10 days and stools on days 4-10. 'Doggie bags' containing » portions of foods consumed were saved during the first 7 days. Gluten in food, stool and urine was quantified using A1/G12 ELISA. RESULTS: Eighteen participants with CD (12 female; age 21-70 years) and three participants on a gluten-containing diet enrolled and completed the study. Twelve out of 18 CD participants had a median 2.1 mg gluten per exposure (range 0.2 to >80 mg). Most exposures were asymptomatic and unsuspected. There was high intra-individual variability in the interval between gluten ingestion and excretion. Participants were generally unable to identify the food. CONCLUSIONS: Gluten exposure on a GFD is common, intermittent, and usually silent. Excretion kinetics are highly variable among individuals. The amount of gluten varied widely, but was typically in the milligram range, which was 10-100 times less than consumed by those on an unrestricted diet. These findings suggest that a strict GFD is difficult to attain, and specific exposures are difficult to detect due to variable time course of excretion.


Assuntos
Doença Celíaca/metabolismo , Dieta Livre de Glúten , Exposição Dietética/análise , Glutens/farmacocinética , Adulto , Idoso , Doença Celíaca/urina , Ingestão de Alimentos , Fezes/química , Feminino , Contaminação de Alimentos/análise , Glutens/análise , Glutens/urina , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Am J Clin Nutr ; 112(5): 1240-1251, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-32692806

RESUMO

BACKGROUND: The treatment of celiac disease (CD) is a lifelong gluten-free diet (GFD). The current methods for monitoring GFD conformance, such as a dietary questionnaire or serology tests, may be inaccurate in detecting dietary transgressions, and duodenal biopsies are invasive, expensive, and not a routine monitoring technique. OBJECTIVES: Our aim was to determine the clinical usefulness of urine gluten immunogenic peptides (GIP) as a biomarker monitoring GFD adherence in celiac patients and to evaluate the concordance of the results with the degree of mucosal damage. METHODS: A prospective observational study was conducted involving 22 de novo CD patients, 77 celiac patients consuming a GFD, and 13 nonceliac subjects. On 3 d of the week, urine samples were collected and the GIP concentrations were tested. Simultaneously, anti-tissue transglutaminase antibodies, questionnaire results, clinical manifestations, and histological findings were analyzed. RESULTS: Approximately 24% (18 of 76) of the celiac patients consuming a GFD exhibited Marsh II-III mucosal damage. Among this population, 94% (17 of 18) had detectable urine GIP; however, between 60% and 80% were asymptomatic and exhibited negative serology and appropriate GFD adherence based on the questionnaire. In contrast, 97% (31 of 32) of the celiac patients without duodenal damage had no detectable GIP. These results demonstrated the high sensitivity (94%) and negative predictive value (97%) of GIP measurements in relation to duodenal biopsy findings. In the de novo CD-diagnosed cohort, 82% (18 of 22) of patients had measurable amounts of GIP in the urine. CONCLUSIONS: Determining GIP concentrations in several urine samples may be an especially convenient approach to assess recent gluten exposure in celiac patients and appears to accurately predict the absence of histological lesions. The introduction of GIP testing as an assessment technique for GFD adherence may help in ascertaining dietary compliance and to target the most suitable intervention during follow-up.


Assuntos
Doença Celíaca/urina , Dieta Livre de Glúten , Glutens/imunologia , Mucosa Intestinal/patologia , Adulto , Idoso , Doença Celíaca/dietoterapia , Doença Celíaca/imunologia , Doença Celíaca/patologia , Feminino , Humanos , Mucosa Intestinal/metabolismo , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Valor Preditivo dos Testes , Urinálise , Adulto Jovem
15.
Aliment Pharmacol Ther ; 49(12): 1484-1492, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31074004

RESUMO

BACKGROUND: Treatment for coeliac disease is a lifelong strict gluten-free diet. Although guidelines recommend regular follow-up with dietary interviews and coeliac serology, these methods may be inaccurate. AIM: To evaluate the usefulness of faecal gluten immunogenic peptides to support the diagnosis and to determine the adherence to the gluten-free diet in coeliac children. METHODS: Multicentre prospective observational study including 64 coeliac children. Faecal gluten peptides, and tissue transglutaminase and deamidated gliadin peptide antibodies were analyzed at diagnosis, and 6, 12 and 24 months thereafter. Gluten consumption was estimated from gluten peptide levels. RESULTS: Most children (97%) had detectable gluten peptides at diagnosis. On a gluten-free diet, the rate of gluten peptides increased from 13% at 6 months to 25% at 24 months. Mean estimated gluten exposure dropped from 5543 mg/d at diagnosis to 144 mg/d at 6 months, then increased to 606 mg/d by 24 months. In contrast, deamidated gliadin peptide antibodies normalised and only 20% had elevated tissue transglutaminase antibody by 24 months. The elevation of tissue transglutaminase antibody was more prolonged in patients with detectable gluten peptides (P < 0.05). Nevertheless, absolute levels of tissue transglutaminase antibody had low sensitivity to identify patients with detectable gluten peptides (P > 0.1). Dietitian assessment was only moderately correlated with gluten peptide detection (κ = 0.5). CONCLUSIONS: Faecal gluten peptides testing may guide treatment of coeliac disease prior to diagnosis and during the assessment diet adherence. Further studies could determine if early identification of gluten exposure reduces the need for expensive/invasive investigations for non-responsive coeliac disease. ClinicalTrials.gov Number: NCT02711397.


Assuntos
Doença Celíaca/metabolismo , Fezes/química , Glutens/química , Peptídeos/análise , Adolescente , Anticorpos/sangue , Doença Celíaca/dietoterapia , Criança , Pré-Escolar , Dieta Livre de Glúten , Feminino , Humanos , Lactente , Masculino , Peptídeos/imunologia , Transglutaminases/imunologia
16.
Nutrients ; 11(2)2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30678169

RESUMO

The high global demand of wheat and its subsequent consumption arise from the physicochemical properties of bread dough and its contribution to the protein intake in the human diet. Gluten is the main structural complex of wheat proteins and subjects affected by celiac disease (CD) cannot tolerate gluten protein. Within gluten proteins, α-gliadins constitute the most immunogenic fraction since they contain the main T-cell stimulating epitopes (DQ2.5-glia-α1, DQ2.5-glia-α2, and DQ2.5-glia-α3). In this work, the celiac immunotoxic potential of α-gliadins was studied within Triticeae: diploid, tetraploid, and hexaploid species. The abundance and immunostimulatory capacity of CD canonical epitopes and variants (with one or two mismatches) in all α-gliadin sequences were determined. The results showed that the canonical epitopes DQ2.5-glia-α1 and DQ2.5-glia-α3 were more frequent than DQ2.5-glia-α2. A higher abundance of canonical DQ2.5-glia-α1 epitope was found to be associated with genomes of the BBAADD, AA, and DD types; however, the abundance of DQ2.5-glia-α3 epitope variants was very high in BBAADD and BBAA wheat despite their low abundance in the canonical epitope. The most abundant substitution was that of proline to serine, which was disposed mainly on the three canonical DQ2.5 domains on position 8. Interestingly, our results demonstrated that the natural introduction of Q to H at any position eliminates the toxicity of the three T-cell epitopes in the α-gliadins. The results provided a rational approach for the introduction of natural amino acid substitutions to eliminate the toxicity of three T-cell epitopes, while maintaining the technological properties of commercial wheats.


Assuntos
Aegilops/química , Doença Celíaca/imunologia , Epitopos/genética , Variação Genética , Gliadina/imunologia , Triticum/química , Aegilops/genética , Aegilops/imunologia , Sequência de Aminoácidos , Proliferação de Células , Criança , Gliadina/genética , Humanos , Leucócitos Mononucleares/fisiologia , Ploidias , Linfócitos T , Triticum/genética , Triticum/imunologia
17.
Nutrients ; 10(12)2018 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-30545051

RESUMO

The study evaluated the symptoms, acceptance, and digestibility of bread made from transgenic low-gliadin wheat, in comparison with gluten free bread, in Non-coeliac gluten sensitivity (NCGS) patients, considering clinical/sensory parameters and gut microbiota composition. This study was performed in two phases of seven days each, comprising a basal phase with gluten free bread and an E82 phase with low-gliadin bread. Gastrointestinal clinical symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, and stool samples were collected for gluten immunogenic peptides (GIP) determination and the extraction of gut microbial DNA. For the basal and E82 phases, seven and five patients, respectively, showed undetectable GIPs content. The bacterial 16S rRNA gene V1-V2 hypervariable regions were sequenced using the Illumina MiSeq platform and downstream analysis was done using a Quantitative Insights into Microbial Ecology (QIIME) pipeline. No significant differences in the GSRS questionnaires were observed between the two phases. However, we observed a significantly lower abundance of some gut genera Oscillospira, Dorea, Blautia, Bacteroides, Coprococcus, and Collinsella, and a significantly higher abundance of Roseburia and Faecalibacterium genera during the E82 phase compared with the basal phase. The consumption of low-gliadin bread E82 by NCGS subjects induced potentially positive changes in the gut microbiota composition, increasing the butyrate-producing bacteria and favoring a microbial profile that is suggested to have a key role in the maintenance or improvement of gut permeability.


Assuntos
Dieta Livre de Glúten/estatística & dados numéricos , Microbioma Gastrointestinal/fisiologia , Gliadina/efeitos adversos , Gliadina/análise , Síndromes de Malabsorção/dietoterapia , Adulto , Fezes/química , Fezes/microbiologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Plantas Geneticamente Modificadas/genética , Triticum/genética
19.
Metas enferm ; 20(2): 54-60, mar. 2017. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-161334

RESUMO

El tratamiento con fármacos anticoagulantes hace que el paciente que lo toma tenga el riesgo de presentar un hematoma subcutáneo ante un mínimo traumatismo, cuyas consecuencias serán variables en función de la zona donde se produzca, las condiciones del paciente, así como del adecuado tratamiento del mismo. Se expone el caso de un paciente varón de 85 años de edad en tratamiento con acecumarol, que tras sufrir una caída accidental presentó hematoma subcutáneo en extremidad inferior izquierda, siendo derivado al Hospital Comarcal de Alcañiz (Teruel) ante la persistencia y mala evolución del mismo. Se realiza una valoración enfermera según el modelo de Virginia Henderson y se establecen diagnósticos de Enfermería desarrollando el plan de cuidados, para ello se utilizan las clasificaciones de North American Nursing Diagnosis Association (NANDA), Nursing Outcome Classification (NOC) y Nursing Interventions Classification (NIC). Al seguir un plan de cuidados individualizado y con el uso de la terapia de presión negativa (TPN) como eje principal del tratamiento de heridas complejas y de amplia extensión, se consiguió una rápida y satisfactoria resolución de la herida gracias al trabajo de un equipo multidisciplinar


Anticoagulant drug treatment leads patients to be at risk of presenting a subcutaneous hematoma caused even by a minor injury, with consequences that will vary according to the area where it appears and patient status, as well as to the adequate treatment received. We present the case of a male 85-year-old patient on treatment with acecoumarol who, after an accidental fall, presented a subcutaneous hematoma in his lower left limb, and was referred to the Hospital Comarcal de Alcañiz (Teruel) due to its persistence and bad evolution. Nursing assessment was conducted according to Virginia Henderson’s model, and nursing diagnosis was established for developing the plan of care, using the classifications by the North American Nursing Diagnosis Association (NANDA), Nursing Outcome Classification (NOC) and Nursing Interventions Classification (NIC). By following an individualized plan of care and using Negative Pressure Therapy (NTP) as the cornerstone for the treatment of complex and large wounds, a fast and satisfactory solution was found for the wound, through the work of a multidisciplinary team


Assuntos
Humanos , Masculino , Idoso de 80 Anos ou mais , Tratamento de Ferimentos com Pressão Negativa/métodos , Cicatrização/fisiologia , Anticoagulantes , Técnicas de Fechamento de Ferimentos , Diagnóstico de Enfermagem/métodos
20.
Am J Gastroenterol ; 111(10): 1456-1465, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27644734

RESUMO

OBJECTIVES: Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring. METHODS: We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously. RESULTS: Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP. CONCLUSIONS: Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397.


Assuntos
Autoanticorpos/imunologia , Doença Celíaca/dietoterapia , Registros de Dieta , Dieta Livre de Glúten , Fezes/química , Proteínas de Ligação ao GTP/imunologia , Gliadina/imunologia , Glutens/análise , Imunoglobulina A/imunologia , Cooperação do Paciente , Transglutaminases/imunologia , Adolescente , Fatores Etários , Anticorpos/imunologia , Estudos de Casos e Controles , Doença Celíaca/imunologia , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Proteína 2 Glutamina gama-Glutamiltransferase , Testes Sorológicos , Inquéritos e Questionários , Adulto Jovem
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