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1.
Medicine (Baltimore) ; 99(35): e21488, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871870

RESUMO

BACKGROUND: Celiac disease is an autoimmune enteropathy characterized by an aberrant immune response to ingested gluten in genetically predisposed individuals. Studies have pointed to a rising prevalence of celiac disease in recent decades. Changes in diet and use of medication that may impact the gut microbiome have been suggested as potential contributors. Exposure to proton pump inhibitors (PPIs) was recently found to be associated with an increased risk for subsequent diagnosis of celiac disease. We aimed to investigate potential mechanisms for this link by examining the relationship between PPI use and gluten-related immune responses in the context of changes in gut microbiome. METHODS: We performed a post hoc analysis of blood and fecal samples from a recent randomized trial in order to assess the potential association between PPI use and development of celiac disease serology in conjunction with alterations in gastrointestinal microbial composition. The study included 12 healthy participants who were administered a PPI (Omeprazole; 40 mg twice daily) for 4 or 8 weeks. RESULTS: The analysis did not reveal an overall significant change in levels of serologic markers of celiac disease for the study cohort in response to PPI treatment. However, one individual developed a marked increase in the celiac disease-specific autoantibody response to transglutaminase 2 in conjunction with enhanced immune reactivity to gluten during the trial. Genotyping revealed positivity for the celiac disease-associated HLA-DQ2 and -DQ8 alleles. Furthermore, the observed elevation in antibody responses was closely associated with a sharp increase in fecal abundance of bacteria of the order Actinomycetales. CONCLUSIONS: The results of this exploratory analysis support further investigation of molecular mechanisms involved in the contribution of PPIs to celiac disease risk through the potential enhancement of gluten immunopathology and changes in gut microbial population.


Assuntos
Doença Celíaca/sangue , Doença Celíaca/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Omeprazol/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Actinomycetales/crescimento & desenvolvimento , Adulto , Alelos , Doença Celíaca/epidemiologia , Doença Celíaca/metabolismo , Fezes/microbiologia , Feminino , Proteínas de Ligação ao GTP/sangue , Proteínas de Ligação ao GTP/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Genótipo , Glutens/efeitos adversos , Glutens/imunologia , Antígenos HLA-DQ/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/uso terapêutico , Prevalência , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Transglutaminases/sangue , Transglutaminases/efeitos dos fármacos
2.
Am J Gastroenterol ; 115(10): 1584-1595, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32740074

RESUMO

INTRODUCTION: Many patients with celiac disease (CD) experience persistent symptoms despite adhering to the gluten-free diet. Different studies have assessed the use of probiotics as an adjuvant treatment for CD. We performed a systematic review and meta-analysis to evaluate the efficacy of probiotics in improving gastrointestinal (GI) symptoms and quality of life (QOL) in patients with CD. METHODS: We searched EMBASE, MEDLINE, CINAHL, Web of Science, CENTRAL, and DARE databases up to February 2019 for randomized controlled trials (RCTs) evaluating probiotics compared with placebo for treating CD. We collected data on GI symptoms, QOL, adverse events, serum tumor necrosis factor-α, intestinal permeability, and microbiota composition. RESULTS: We screened 2,831 records and found that 7 articles describing 6 RCTs (n = 5,279 participants) were eligible for quantitative analysis. Probiotics improved GI symptoms when assessed by the GI Symptoms Rating Scale (mean difference symptom reduction: 228.7%; 95% confidence interval [CI] 243.96-213.52; P = 0.0002). There was no difference in GI symptoms after probiotics when different questionnaires were pooled. The levels of Bifidobacteria increased after probiotics (mean difference: 0.85 log colony-forming units (CFU) per gram; 95% CI 0.38-1.32 log CFU per gram; P = 0.0003). There were insufficient data on tumor necrosis factor-a levels or QOL for probiotics compared with placebo. No difference in adverse events was observed between probiotics and placebo. The overall certainty of the evidence ranged from very low to low. DISCUSSION: Probiotics may improve GI symptoms in patients with CD. High-quality clinical trials are needed to improve the certainty in the evidence (see Visual abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B595).


Assuntos
Doença Celíaca/terapia , Dieta Livre de Glúten , Microbioma Gastrointestinal , Probióticos/uso terapêutico , Qualidade de Vida , Doença Celíaca/sangue , Doença Celíaca/microbiologia , Doença Celíaca/fisiopatologia , Humanos , Mucosa Intestinal/metabolismo , Permeabilidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa/sangue
3.
J Pediatr ; 224: 158-161.e2, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32593411

RESUMO

Current screening guidelines in North America for celiac disease recommend additional IgG based testing for younger children. Our multicenter retrospective study showed that the anti-tissue transglutaminase IgA antibody test should be the recommended initial test in all children, including those ≤24 months of age.


Assuntos
Doença Celíaca/sangue , Proteínas de Ligação ao GTP/sangue , Transglutaminases/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Celíaca/diagnóstico , Feminino , Humanos , Deficiência de IgA/sangue , Imunoglobulina A/sangue , Lactente , Masculino , Estudos Retrospectivos
4.
Arch Gynecol Obstet ; 302(5): 1263-1269, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32594297

RESUMO

PURPOSE: The aim of the study was to determine whether celiac disease affects ovarian reserve assessed by antral follicle counting, ovarian volume, and anti-müllerian hormone in adolescent patients. METHODS: This case-control multicenter trial was performed from January 1, 2017 to May 31, 2018 and included 45 girls. On days 2-5 of the menstrual cycle, measurements of serum follicle stimulating hormone, luteinizing hormone, estradiol, prolactin, and anti-müllerian hormone were performed. Antral follicle counts and ovarian volumes were determined on the same day. RESULTS: Evaluation was made of 21 (47.7%) celiac patients with a mean age of 15.8 ± 1.3 years, and 24 (52.3%) healthy control subjects with a mean age of 16.2 ± 1.2. There was no difference between the groups in respect of right and left ovarian volumes (p = 0.790 and p = 0.670, respectively). Serum levels of anti-müllerian hormone of the celiac patients and controls were found comparable [(3.7 ± 2.9 (0.5-12) and 3.6 ± 1.8 (1.2-8.1)] ng/mL, respectively, p = 0.915). CONCLUSIONS: Celiac disease may not affect the ovarian reserve determined with established ovarian reserve markers including antral follicle counting, ovarian volume, and anti-müllerian hormone in adolescent patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier (NCT number): NCT04024449 https://clinicaltrials.gov/ct2/show/NCT04024449.


Assuntos
Hormônio Antimülleriano/sangue , Doença Celíaca/fisiopatologia , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Reserva Ovariana , Adolescente , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Celíaca/sangue , Estradiol/sangue , Feminino , Humanos , Ciclo Menstrual , Folículo Ovariano , Ovário , Prolactina/sangue , Adulto Jovem
5.
J Pediatr ; 223: 87-92.e1, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32381465

RESUMO

OBJECTIVE: To study the optimal cut-off value for anti-tissue transglutaminase type 2 IgA antibodies (TG2A) in serum to select for diagnostic small bowel biopsies for celiac disease in children with type 1 diabetes mellitus. STUDY DESIGN: Children with type 1 diabetes mellitus with elevated TG2A titers and duodenal biopsies performed during the course of their diabetes treatment were included. Anti-endomysial antibodies were recorded if present. The optimal TG2A cut-off value, expressed as the ratio between obtained value and upper limit of normal (ULN), was determined using receiver operating characteristic curve analysis and compared with the cut-off value used in the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines in terms of sensitivity, specificity, positive and negative predictive value. RESULTS: We included 63 children. The optimal cut-off value for performing biopsies is demonstrated to be 11 times the ULN. Raising the cut-off value from 3 times the ULN to 11 times the ULN changed sensitivity from 96% to 87% and increased specificity from 36% to 73%, increased the positive predictive value from 88% to 94% and lowered negative predictive value from 67% to 53%. The percentage of normal histology was decreased from 12% to 6%. CONCLUSIONS: Increasing the TG2A cut-off value for performing duodenal biopsies in children with type 1 diabetes mellitus and suspected celiac disease leads to a substantial reduction of unnecessary biopsies. We advocate to adapt the European Society for Pediatric Gastroenterology, Hepatology and Nutrition 2012 guidelines for this group of children, including monitoring patients with TG2A levels of less than 11 times the ULN over time.


Assuntos
Doença Celíaca/diagnóstico , Diabetes Mellitus Tipo 1/complicações , Proteínas de Ligação ao GTP/sangue , Transglutaminases/sangue , Adolescente , Anticorpos , Biópsia/efeitos adversos , Doença Celíaca/sangue , Doença Celíaca/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Intestino Delgado/imunologia , Masculino , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Procedimentos Desnecessários
6.
Nutrients ; 12(4)2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32230847

RESUMO

Background: Adults with celiac disease (CeD) show low bone mineral density (BMD) and high fracture risk. CeD guidelines suggest measurements of serum minerals and vitamin D. However, studies on vitamin levels in CeD patients are contradictory. Aim: To investigate in CeD, 25-hydroxy-vitamin D [25(OH)D], 1,25-dihydroxy-vitamin D [1,25(OH)2D], and related analytes and to evaluate their relationships to peripheral BMD as assessed by peripheral quantitative computed tomography (pQCT). Methods: Gluten-free diet (GFD)-treated, and untreated adult CeD patients naïve to vitamin D and calcium supplementation underwent measurements of serum 25(OH)D, 1,25(OH)2D, parathyroid hormone (PTH), total calcium, phosphate, and of radius BMD by pQCT. Results: Complete data were collected in 105 patients for lab tests and 87 patients for BMD. For lab tests, untreated CeD differed from treated CeD for 22.0% lower serum 25(OH)D (p = 0.023), 42.5% higher serum PTH (p < 0.001), and 13.0% higher serum 1,25(OH)2D (p = 0.029) in the presence of similar serum calcium and phosphorus (p > 0.35). For BMD, untreated CeD differed from treated CeD for lower diaphyseal cortical BMD (1133 and 1157 mg/cm3, p = 0.004) but not for distal BMD (total, trabecular, and subcortical, p > 0.13). Independent correlates of diaphyseal cortical BMD were GFD treatment and body mass index (p < 0.05). Conclusions: Data indicated that, compared to CeD patients on a gluten-free diet, untreated adult CeD patients at diagnosis had lower 25(OH)D, higher PTH, and higher 1,25(OH)2D in the absence of difference in serum calcium and phosphorus. 25(OH)D and 1,25(OH)2D, even below the normal range, were not associated with BMD. Our findings do not support the use of vitamin D supplementation for all CeD adults.


Assuntos
Densidade Óssea/fisiologia , Doença Celíaca , Vitamina D/análogos & derivados , Adulto , Doença Celíaca/sangue , Doença Celíaca/dietoterapia , Doença Celíaca/epidemiologia , Doença Celíaca/fisiopatologia , Dieta Livre de Glúten , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Estudos Prospectivos , Vitamina D/sangue
7.
Nutrients ; 12(3)2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32245180

RESUMO

The current study assesses whether the use of a gluten-free diet (GFD) is sufficient for maintaining correct iron status in children with celiac disease (CD). The study included 101 children. The celiac group (n = 68) included children with CD, with long (> 6 months) (n = 47) or recent (< 6 months) (n = 21) adherence to a GFD. The control group (n = 43) included healthy children. Dietary assessment was performed by a food frequency questionnaire and a 3-day food record. Celiac children had lower iron intake than controls, especially at the beginning of GFD (p < 0.01). The group CD-GFD >6 months showed a higher intake of cobalamin, meat derivatives and fish compared to that of CD-GFD <6 months (all, p < 0.05). The control group showed a higher consumption of folate, iron, magnesium, selenium and meat derivatives than that of children CD-GFD >6 months (all, p < 0.05). Control children also showed a higher consumption of folate and iron compared to that of children CD-GFD <6 months (both, p < 0.05). The diet of celiac children was nutritionally less balanced than that of the control. Participation of dietitians is necessary in the management of CD to guide the GFD as well as assess the inclusion of iron supplementation and other micronutrients that may be deficient.


Assuntos
Doença Celíaca/dietoterapia , Doença Celíaca/epidemiologia , Dieta Livre de Glúten , Micronutrientes , Avaliação Nutricional , Estado Nutricional , Adolescente , Biomarcadores , Análise Química do Sangue , Pesos e Medidas Corporais , Estudos de Casos e Controles , Doença Celíaca/sangue , Criança , Feminino , Humanos , Masculino
8.
Autoimmun Rev ; 19(5): 102513, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32173515

RESUMO

BACKGROUND: The clinical presentation of celiac disease (CD) varies between children. The objective of this study was to document the pre-test probability for CD based on symptoms and routine laboratory test and to evaluate the performance of two IgA anti-tissue transglutaminase (tTG) assays. We critically reviewed the concept of using multiples of the manufacturer's upper limit of normal (ULN), as proposed in the ESPGHAN guidelines (if IgA tTG is >10 times ULN, no biopsy is needed). METHODS: The retrospective study included 91 children with newly diagnosed CD and 605 controls (<16 years). All underwent upper endoscopy with small bowel biopsies. Four laboratory parameters and 16 symptoms were registered. All patients were tested for IgA anti-tTG antibodies with assays from Inova Diagnostics and Thermo Fisher Scientific. RESULTS: Some combinations of clinical symptoms and laboratory parameters had a high pre-test probability for CD, such as (combinations of) anorexia, failure to thrive, low ferritin level and elevated AST. The diagnostic performance of both IgA anti-tTG assays was excellent and comparable (no difference in ROC curve area under the curve). At a threshold that corresponds to a specificity of 100% (5 times ULN for Inova Diagnostics and 2 times ULN for Thermo Fisher), the sensitivity was 82% for both assays. At the 10 times ULN threshold, the sensitivity differed between the assays (77% vs. 57%), indicating that such threshold does not completely align interpretation across companies. CONCLUSIONS: Our study showed that some combinations of symptoms and aberrant laboratory parameters had a high pre-test probability. The use of the ESPGHAN non-biopsy approach could reduce small bowel biopsies, but thresholds for IgA-tTG levels are not aligned across assays and should be based on predefined likelihood ratios or specificity.


Assuntos
Doença Celíaca/sangue , Doença Celíaca/diagnóstico , Adolescente , Autoanticorpos/sangue , Autoanticorpos/imunologia , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade , Transglutaminases/imunologia
9.
Gastroenterology ; 158(6): 1667-1681.e12, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32032584

RESUMO

BACKGROUND & AIMS: Celiac disease could be treated, and potentially cured, by restoring T-cell tolerance to gliadin. We investigated the safety and efficacy of negatively charged 500-nm poly(lactide-co-glycolide) nanoparticles encapsulating gliadin protein (TIMP-GLIA) in 3 mouse models of celiac disease. Uptake of these nanoparticles by antigen-presenting cells was shown to induce immune tolerance in other animal models of autoimmune disease. METHODS: We performed studies with C57BL/6; RAG1-/- (C57BL/6); and HLA-DQ8, huCD4 transgenic Ab0 NOD mice. Mice were given 1 or 2 tail-vein injections of TIMP-GLIA or control nanoparticles. Some mice were given intradermal injections of gliadin in complete Freund's adjuvant (immunization) or of soluble gliadin or ovalbumin (ear challenge). RAG-/- mice were given intraperitoneal injections of CD4+CD62L-CD44hi T cells from gliadin-immunized C57BL/6 mice and were fed with an AIN-76A-based diet containing wheat gluten (oral challenge) or without gluten. Spleen or lymph node cells were analyzed in proliferation and cytokine secretion assays or by flow cytometry, RNA sequencing, or real-time quantitative polymerase chain reaction. Serum samples were analyzed by gliadin antibody enzyme-linked immunosorbent assay, and intestinal tissues were analyzed by histology. Human peripheral blood mononuclear cells, or immature dendritic cells derived from human peripheral blood mononuclear cells, were cultured in medium containing TIMP-GLIA, anti-CD3 antibody, or lipopolysaccharide (controls) and analyzed in proliferation and cytokine secretion assays or by flow cytometry. Whole blood or plasma from healthy volunteers was incubated with TIMP-GLIA, and hemolysis, platelet activation and aggregation, and complement activation or coagulation were analyzed. RESULTS: TIMP-GLIA did not increase markers of maturation on cultured human dendritic cells or induce activation of T cells from patients with active or treated celiac disease. In the delayed-type hypersensitivity (model 1), the HLA-DQ8 transgenic (model 2), and the gliadin memory T-cell enteropathy (model 3) models of celiac disease, intravenous injections of TIMP-GLIA significantly decreased gliadin-specific T-cell proliferation (in models 1 and 2), inflammatory cytokine secretion (in models 1, 2, and 3), circulating gliadin-specific IgG/IgG2c (in models 1 and 2), ear swelling (in model 1), gluten-dependent enteropathy (in model 3), and body weight loss (in model 3). In model 1, the effects were shown to be dose dependent. Splenocytes from HLA-DQ8 transgenic mice given TIMP-GLIA nanoparticles, but not control nanoparticles, had increased levels of FOXP3 and gene expression signatures associated with tolerance induction. CONCLUSIONS: In mice with gliadin sensitivity, injection of TIMP-GLIA nanoparticles induced unresponsiveness to gliadin and reduced markers of inflammation and enteropathy. This strategy might be developed for the treatment of celiac disease.


Assuntos
Doença Celíaca/tratamento farmacológico , Gliadina/administração & dosagem , Tolerância Imunológica/efeitos dos fármacos , Nanopartículas/administração & dosagem , Administração Intravenosa , Animais , Linfócitos T CD4-Positivos , Doença Celíaca/sangue , Doença Celíaca/imunologia , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Gliadina/imunologia , Gliadina/toxicidade , Glutens/administração & dosagem , Glutens/imunologia , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/imunologia , Humanos , Mucosa Intestinal , Leucócitos Mononucleares , Camundongos , Camundongos Transgênicos , Nanopartículas/química , Nanopartículas/toxicidade , Poliglactina 910/química , Cultura Primária de Células , Testes de Toxicidade Aguda
10.
Aliment Pharmacol Ther ; 51(7): 699-705, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32048756

RESUMO

BACKGROUND: The causes of seronegative villous atrophy can be grouped as coeliac or noncoeliac related. There is no consensus on how to approach subjects with seronegative coeliac disease. AIM: To evaluate the accuracy of both an increase in CD3+ T-cell receptor gamma delta+ (TCRγδ+ ) intraepithelial lymphocytes and coeliac lymphogram for the diagnosis of coeliac disease in patients with seronegative villous atrophy. METHODS: Sixty-seven consecutive patients with seronegative villous atrophy were included. Duodenal biopsies to assess TCRγδ+ and CD3- by flow cytometry were performed at the index endoscopy. Coeliac lymphogram was defined as an increase in TCRγδ+ plus a decrease in CD3- intraepithelial lymphocytes. Sensitivity, specificity and Fagan's nomogram were calculated. RESULTS: Coeliac disease was diagnosed in 37 patients and noncoeliac villous atrophy in 30. Coeliac patients were younger (39 ± 3 vs 55 ± 3 years; P = 0.001), more often showed HLA-DQ2/8 (97.6% vs 61%; P = 0.002) and had a more severe histology (61% vs 32% Marsh 3b-c; P = 0.055), as compared to noncoeliac ones. Coeliac lymphogram was associated with a sensitivity of 87% (CI, 73.7-95) and specificity of 96.7% (82.7-99.9), whereas evaluating only TCRγδ+ yielded a sensitivity of 91.3% (79.2-97.6) and specificity of 83.3% (65.3-94.3). Among patients with a pre-test coeliac disease probability of 30%, post-test probabilities were 92% and 5% for positive and negative coeliac lymphogram, and 70% and 4% for positive and negative TCRγδ+ . CONCLUSIONS: Coeliac lymphogram was associated with a high level of diagnostic evidence either against or in favour of coeliac disease in patients with seronegative villous atrophy.


Assuntos
Doença Celíaca/diagnóstico , Mucosa Intestinal/patologia , Linfócitos Intraepiteliais/metabolismo , Linfócitos Intraepiteliais/patologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Adulto , Atrofia/complicações , Atrofia/diagnóstico , Atrofia/imunologia , Atrofia/patologia , Biópsia , Estudos de Casos e Controles , Doença Celíaca/sangue , Doença Celíaca/imunologia , Doença Celíaca/patologia , Progressão da Doença , Feminino , Citometria de Fluxo , Humanos , Mucosa Intestinal/imunologia , Intestinos/imunologia , Intestinos/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sintomas Prodrômicos , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Testes Sorológicos
11.
Expert Rev Gastroenterol Hepatol ; 14(3): 147-154, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32011187

RESUMO

Introduction: This article provides a comprehensive overview of the development and application of serological tests used routinely in clinical practice for the diagnosis and management of adult celiac disease.Areas covered: We summarize existing scientific literature related to anti-endomyseal, anti-tissue transglutaminase, and anti-deamidated gliadin peptide antibodies and detail the current and potential future applications of these tests in celiac disease.Expert commentary: Current serological tests in celiac disease have some of the best performance characteristics among disease-specific tests. However, in adult celiac disease, current diagnostic algorithms still rely on duodenal biopsies to confirm the diagnosis. A 'biopsy avoidance strategy' has been implemented in pediatric celiac disease. Future high-quality studies will help inform on whether this approach can be implemented into adult gastroenterology services. It is envisaged that the next 5 years will see an increasing reliance on serology in the diagnosis of adult celiac disease.


Assuntos
Autoanticorpos/sangue , Doença Celíaca/diagnóstico , Testes Sorológicos , Adulto , Autoanticorpos/imunologia , Biópsia , Doença Celíaca/sangue , Doença Celíaca/imunologia , Doença Celíaca/terapia , Continuidade da Assistência ao Paciente , Dieta Livre de Glúten , Duodeno/patologia , Gliadina/sangue , Gliadina/imunologia , Humanos , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/imunologia , Testes Sorológicos/métodos , Testes Sorológicos/tendências , Transglutaminases/sangue , Transglutaminases/imunologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-31952137

RESUMO

Celiac disease (CD) is an immunological disorder that mainly affects the small intestine, generating an inflammatory process in response to the presence of gluten (a protein). Autoimmune diseases are part of a group of diseases that are difficult to diagnose without a specific protocol or consensus to detect them due to the number of symptoms and diseases with which it has a relationship. Therefore, the aim of this review was to analyze the diagnostic tools of CD used in middle-aged women, to compare the use and effectiveness of the different tools, and to propose a strategy for the use of the tools based on the results found in the literature. The present research followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The search was conducted in the following databases: Scielo, PubMed, Web of Science, and Worldwide Science org. In the initial literature search, 2004 titles and relevant abstracts were found. Among them, 687 were duplicates, leaving 1130 articles. Based on the inclusion criteria, only 41 articles passed the selection process; 4 main types of analyses appear in the studies: blood tests, questionnaires, clinical history, and biopsy. It can be said that none of the analyses have a 100% reliability since most of them can present false negatives; therefore, the best way to diagnose celiac disease up to now is through a combination of different tests (Immunoglobulin A and small intestinal biopsy).


Assuntos
Doença Celíaca/diagnóstico , Doença Celíaca/sangue , Doença Celíaca/patologia , Feminino , Humanos , Imunoglobulina A/sangue , Intestino Delgado/patologia , Reprodutibilidade dos Testes
13.
Clin Exp Immunol ; 199(1): 68-78, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505020

RESUMO

Cytokines have been extensively studied in coeliac disease, but cytokine release related to exposure to gluten and associated symptoms has only recently been described. Prominent, early elevations in serum interleukin (IL)-2 after gluten support a central role for T cell activation in the clinical reactions to gluten in coeliac disease. The aim of this study was to establish a quantitative hierarchy of serum cytokines and their relation to symptoms in patients with coeliac disease during gluten-mediated cytokine release reactions. Sera were analyzed from coeliac disease patients on a gluten free-diet (n = 25) and from a parallel cohort of healthy volunteers (n = 25) who underwent an unmasked gluten challenge. Sera were collected at baseline and 2, 4 and 6 h after consuming 10 g vital wheat gluten flour; 187 cytokines were assessed. Confirmatory analyses were performed by high-sensitivity electrochemiluminescence immunoassay. Cytokine elevations were correlated with symptoms. Cytokine release following gluten challenge in coeliac disease patients included significant elevations of IL-2, chemokine (C-C motif) ligand 20 (CCL20), IL-6, chemokine (C-X-C motif) ligand (CXCL)9, CXCL8, interferon (IFN)-γ, IL-10, IL-22, IL-17A, tumour necrosis factor (TNF)-α, CCL2 and amphiregulin. IL-2 and IL-17A were earliest to rise. Peak levels of cytokines were generally at 4 h. IL-2 increased most (median 57-fold), then CCL20 (median 10-fold). Cytokine changes were strongly correlated with one another, and the most severely symptomatic patients had the highest elevations. Early elevations of IL-2, IL-17A, IL-22 and IFN-γ after gluten in patients with coeliac disease implicates rapidly activated T cells as their probable source. Cytokine release after gluten could aid in monitoring experimental treatments and support diagnosis.


Assuntos
Doença Celíaca/imunologia , Citocinas/imunologia , Glutens/toxicidade , Ativação Linfocitária/efeitos dos fármacos , Linfócitos T/imunologia , Adulto , Doença Celíaca/sangue , Doença Celíaca/patologia , Citocinas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T/metabolismo , Linfócitos T/patologia
14.
Pediatrics ; 144(4)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31492765

RESUMO

BACKGROUND AND OBJECTIVES: Celiac disease (CeD) is associated with psychopathology in children. It is unknown whether this association is present in children with celiac disease autoimmunity (CDA) identified by screening. We examined the associations between subclinical CDA and emotional and behavioral problems in children without previous CeD diagnosis. METHODS: In a population-based cohort study of 3715 children (median age: 6 years), blood titers of tissue transglutaminase autoantibodies were analyzed. CDA was defined as a measurement of tissue transglutaminase autoantibodies ≥7 U/mL (n = 51). Children with previous CeD diagnosis or children on a gluten-free diet, were excluded. The Child Behavior Checklist (CBCL) was filled in by parents and was used to assess behavioral and emotional problems of children at a median age of 5.9 years. Multiple linear regression models were applied to evaluate the cross-sectional associations between CDA and CBCL scores. Sensitivity analyses were done in a subgroup of children who were seropositive carrying the HLA antigen risk alleles for CeD. RESULTS: In basic models, CDA was not associated with emotional and behavioral problems on the CBCL scales. After adjustment for confounders, CDA was significantly associated with anxiety problems (ß = .29; 95% confidence interval 0.02 to 0.55; P = .02). After exclusion of children who did not carry the HLA-DQ2 and/or HLA-DQ8 risk alleles (n = 4), CDA was additionally associated with oppositional defiant problems (ß = .35; 95% confidence interval 0.02 to 0.69). Associations were not explained by gastrointestinal complaints. CONCLUSIONS: Our results reveal that CDA, especially combined with the HLA-DQ2 and HLA-DQ8 risk alleles, is associated with anxiety problems and oppositional defiant problems. Further research should be used to establish whether behavioral problems are a reflection of subclinical CeD.


Assuntos
Ansiedade/imunologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/imunologia , Doenças Autoimunes/psicologia , Doença Celíaca/imunologia , Doença Celíaca/psicologia , Autoanticorpos/sangue , Doenças Autoimunes/sangue , Doenças Autoimunes/genética , Doença Celíaca/sangue , Doença Celíaca/diagnóstico , Lista de Checagem , Criança , Pré-Escolar , Intervalos de Confiança , Feminino , Proteínas de Ligação ao GTP/imunologia , Antígenos HLA-DQ/sangue , Antígenos HLA-DQ/genética , Humanos , Lactente , Modelos Lineares , Masculino , Comportamento Problema/psicologia , Estudos Prospectivos , Sensibilidade e Especificidade , Fatores Sexuais , Transglutaminases/imunologia
15.
Int Arch Allergy Immunol ; 180(4): 250-254, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31522183

RESUMO

INTRODUCTION: Chronic spontaneous urticaria (CSU) in childhood affects the quality of life of the patient and may be associated with other autoimmune diseases. The aim of this study was to investigate the association of autoimmune diseases with CSU in children. METHODS: In a 3-year period, from 2015 to 2018, forty-nine children were diagnosed with CSU and monitored in the Outpatient Pediatric Allergy Clinic of the University Hospital of Ioannina in Northwestern Greece. The comorbidity with other autoimmune diseases was investigated in this population by autoantibody evaluation. RESULTS: Of the 49 children with CSU, 1 had autoantibodies for celiac disease (CD), which was confirmed by duodenal biopsy via gastroscopy. Four children had high serum levels of anti-thyroid peroxidase antibodies but normal thyroid function. No other specific autoantibodies were detected. CONCLUSION: The prevalence of autoimmune diseases among our children with CSU was low. Nevertheless, we think it is important to test children with CSU for other autoimmune diseases. CD can be diagnosed in children with CSU even in the absence of other indicative signs.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/imunologia , Doença Celíaca/sangue , Urticária Crônica/imunologia , Imunoglobulina E/sangue , Adolescente , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Criança , Pré-Escolar , Urticária Crônica/complicações , Urticária Crônica/patologia , Comorbidade , Feminino , Humanos , Lactente , Masculino , Mastócitos/imunologia
17.
Medicina (Kaunas) ; 55(7)2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31277328

RESUMO

Background and objective: Often micronutrient deficiencies cannot be detected when patient is already following a long-term gluten-free diet with good compliance (LTGFDWGC). The aim of this narrative review is to evaluate the most recent literature that considers blood micronutrient deficiencies in LTGFDWGC subjects, in order to prepare dietary supplementation advice (DSA). Materials and methods: A research strategy was planned on PubMed by defining the following keywords: celiac disease, vitamin B12, iron, folic acid, and vitamin D. Results: This review included 73 studies. The few studies on micronutrient circulating levels in long-term gluten-free diet (LTGFD) patients over 2 years with good compliance demonstrated that deficiency was detected in up to: 30% of subjects for vitamin B12 (DSA: 1000 mcg/day until level is normal, then 500 mcg), 40% for iron (325 mg/day), 20% for folic acid (1 mg/day for 3 months, followed by 400-800 mcg/day), 25% for vitamin D (1000 UI/day or more-based serum level or 50,000 UI/week if level is <20 ng/mL), 40% for zinc (25-40 mg/day), 3.6% of children for calcium (1000-1500 mg/day), 20% for magnesium (200-300 mg/day); no data is available in adults for magnesium. Conclusions: If integration with diet is not enough, starting with supplements may be the correct way, after evaluating the initial blood level to determine the right dosage of supplementation.


Assuntos
Doença Celíaca/dietoterapia , Dieta Livre de Glúten/efeitos adversos , Micronutrientes/análise , Adolescente , Adulto , Cálcio/análise , Cálcio/sangue , Doença Celíaca/sangue , Doença Celíaca/tratamento farmacológico , Criança , Dieta Livre de Glúten/métodos , Suplementos Nutricionais/normas , Feminino , Ácido Fólico/análise , Ácido Fólico/sangue , Humanos , Ferro/análise , Ferro/sangue , Masculino , Micronutrientes/sangue , Cooperação do Paciente/psicologia , Vitamina B 12/análise , Vitamina B 12/sangue , Vitamina D/análise , Vitamina D/sangue , Zinco/análise , Zinco/sangue
19.
Am J Gastroenterol ; 114(10): 1587-1592, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31274511

RESUMO

Celiac disease is a common inflammatory disease triggered by dietary gluten in genetically susceptible individuals. The strongest and best-characterized genetic susceptibilities in celiac disease are class II human leukocyte antigen (HLA) genes known as HLA-DQ2 and DQ8. HLA genetic testing is available through a number of commercial and academic laboratories and is used in the evaluation of celiac disease and to identify at-risk family members. Importantly, HLA genetic testing has a high negative predictive value for celiac disease, but a low positive predictive value. Therefore, for a practicing clinician, it is important to understand when to order HLA genetic testing, what test to order, and how to interpret the result. This review provides a practical primer on HLA genetics in celiac disease.


Assuntos
Doença Celíaca/diagnóstico , Testes Genéticos/normas , Antígenos HLA-DQ/genética , Guias de Prática Clínica como Assunto , Biomarcadores/sangue , Biópsia , Doença Celíaca/sangue , Doença Celíaca/genética , Doença Celíaca/imunologia , Duodeno/imunologia , Duodeno/metabolismo , Duodeno/patologia , Gastroenterologia/normas , Predisposição Genética para Doença , Glutens/imunologia , Glutens/metabolismo , Antígenos HLA-DQ/imunologia , Humanos , Absorção Intestinal/genética , Absorção Intestinal/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Valor Preditivo dos Testes
20.
Oxid Med Cell Longev ; 2019: 7384193, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31320984

RESUMO

Neutrophil-to-lymphocyte ratio (NLR) has been proposed as a bone loss index in postmenopausal women and as a marker of inflammation in coeliac patients. The aims of this work were to evaluate the effect of gluten-free diet (GFD) on NLR retrospectively and study the relationship between NLR and Mediterranean diet adherence and selected food groups (fruits, vegetables, red meat, potatoes, and unrefined and refined cereals). Adult individuals (n = 50), who had been on a strict GFD by at least 6 months, were recruited. The degree of adherence to the Mediterranean diet was calculated with two different scores: the Mediterranean Diet Score (MDS-14), assessed through the validated 14-item questionnaire of the PREDIMED study, and the MEDScore (Score-55) proposed by Panagiotakos. The latter includes the consumption of unrefined cereals (UC). High percentages of osteopenia and osteoporosis were found within the recruited subjects, who furnished the reports of bone mineral density (BMD), in particular in postmenopausal (Post-M) women. Recent NLR was higher in subjects with osteoporosis compared to osteopenia and normal BMD. However, retrospective analysis showed both increase and decrease in NLR after GFD, with no significant differences between Marsh grade, anemia, and BMD status. Moreover, premenopausal previous pregnancy (Pre-MPP) and Post-M had higher NLR at diagnosis compared to Men and premenopausal (Pre-M), but higher differences were observed in recent NLR between Pre-MPP and Men only. Chocolate consumption was associated with lower recent NLR, whereas the latter was correlated with Score-55, but not with MDS-14. Moreover, refined cereal consumption was correlated with recent NLR. Although large prospective studies are needed in order to clarify the relationship between UC and NLR in coeliac patients, in this pilot study, we have investigated for the first time the relationship between NLR, dietary habit, and osteoporosis in coeliac disease.


Assuntos
Doença Celíaca/sangue , Doença Celíaca/dietoterapia , Dieta Mediterrânea , Linfócitos/metabolismo , Neutrófilos/metabolismo , Adulto , Doença Celíaca/patologia , Feminino , Humanos , Masculino , Projetos Piloto
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