RESUMEN
IgE-mediated wheat allergy can take on various forms, including childhood food allergy to wheat, wheat-dependent exercise-induced anaphylaxis in young adults, baker's respiratory allergy/asthma in workers exposed to wheat flour inhalation, and contact urticaria that is caused by hydrolyzed wheat proteins in some cosmetics, and that is sometimes associated with a food allergy. Singleplex and multiplex immunoassays detect specific IgE antibodies to wheat allergenic molecular biomarkers such as omega-5 gliadin Tri a 19, lipid transfer protein Tri a 14, and alpha-amylase inhibitors. The fluorescence enzyme immunoassay with capsulated cellulose polymer solid-phase coupled allergens is a commonly used singleplex assay. Multiplex methods include the ELISA-based macroarray immunoassay using nano-bead technology and a microarray immunoassay on polymer-coated slides. Another promising diagnostic tool is the basophil activation test performed with omega-5 gliadin and other wheat protein types. Detailed comprehension of the structural and immunological features of the numerous wheat allergens significant in clinical settings is imperative for advancing diagnostic biomarkers for IgE-mediated wheat allergies.
Asunto(s)
Alérgenos , Biomarcadores , Gliadina , Inmunoglobulina E , Hipersensibilidad al Trigo , Hipersensibilidad al Trigo/diagnóstico , Hipersensibilidad al Trigo/inmunología , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina E/sangre , Alérgenos/inmunología , Gliadina/inmunología , Triticum/inmunología , Antígenos de Plantas/inmunología , Inmunoensayo/métodosRESUMEN
Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points ⢠The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. ⢠We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. ⢠The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies.
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Autoanticuerpos , Enfermedad Celíaca , Miositis , Humanos , Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/sangre , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/complicaciones , Estudios Transversales , Femenino , Masculino , Persona de Mediana Edad , Adulto , Prevalencia , Autoanticuerpos/sangre , Miositis/inmunología , Miositis/epidemiología , Miositis/sangre , México/epidemiología , Transglutaminasas/inmunología , Anciano , Inmunoglobulina A/sangre , Gliadina/inmunología , Inmunoglobulina G/sangre , Proteína Glutamina Gamma Glutamiltransferasa 2RESUMEN
One-third of people with schizophrenia have elevated levels of anti-gliadin antibodies (AGA IgG). A 5-week randomized double-blind pilot study was performed in 2014-2017 in an inpatient setting to test the effect of a gluten-free diet (GFD) on participants with schizophrenia or schizoaffective disorder who also had elevated AGA IgG (≥ 20 U) but were negative for celiac disease. This earlier pilot study reported that the GFD-group showed improved gastrointestinal and psychiatric symptoms, and also improvements in TNF-α and the inflammatory cytokine IL-23. Here, we performed measurements of these banked plasma samples to detect levels of oxidative stress (OxSt) using a recently developed iridium (Ir)-reducing capacity assay. Triplicate measurements of these samples showed an Intraclass Correlation Coefficient of 0.84 which indicates good reproducibility. Further, a comparison of the OxSt measurements at the baseline and 5-week end-point for this small sample size shows that the GFD-group (N = 7) had lowered OxSt levels compared to the gluten-containing diet group (GCD; N = 9; p = 0.05). Finally, we showed that improvements in OxSt over these 5 weeks were correlated to improvements in gastrointestinal (r = +0.64, p = 0.0073) and psychiatric (r = +0.52, p = 0.039) symptoms. Also, we showed a possible association between the decrease in OxSt and the lowered levels of IL-23 (r = +0.44, p = 0.087), although without statistical significance. Thus, the Ir-reducing capacity assay provides a simple, objective measure of OxSt with the results providing further evidence that inflammation, redox dysregulation and OxSt may mediate interactions between the gut and brain.
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Dieta Sin Gluten , Estrés Oxidativo , Esquizofrenia , Humanos , Esquizofrenia/dietoterapia , Esquizofrenia/sangre , Proyectos Piloto , Estrés Oxidativo/fisiología , Masculino , Adulto , Femenino , Persona de Mediana Edad , Método Doble Ciego , Trastornos Psicóticos/dietoterapia , Trastornos Psicóticos/sangre , Trastornos Psicóticos/inmunología , Gliadina/inmunologíaRESUMEN
Background: Wheat allergy (WA), characterized by immunological responses to wheat proteins, is a gluten-related disorder that has become increasingly recognized in recent years. Bibliometrics involves the quantitative assessment of publications within a specific academic domain. Objectives: We aimed to execute an extensive bibliometric study, focusing on the past 30 years of literature related to wheat allergy. Methods: We searched the Web of Science database on 5th Dec 2023. We used the keywords "wheat allergy or wheat anaphylaxis or wheat hypersensitivity," "gliadin allergy or gliadin anaphylaxis or gliadin hypersensitivity," "wheat-dependent exercise-induced anaphylaxis," and "baker's asthma" for our search. All items published between 1993 and 2023 were included. The top 100 most cited articles were identified and analyzed. Results: Our study conducted an in-depth bibliometric analysis of the 100 most-cited articles in the field of wheat allergy, published between 2002 and 2019. These articles originated from 20 different countries, predominantly Japan and Germany. The majority of these articles were centered on the pathogenesis and treatment of wheat allergy (WA). The Journal of Allergy and Clinical Immunology (JACI) was the most prolific contributor to this list, publishing 14 articles. The article with the highest citation count was published by Biomed Central (BMC) and garnered 748 citations. The peak citation year was 2015, with a total of 774 citations, while the years 1998, 2001, and 2005 saw the highest publication frequency, each with 7 articles. Conclusion: Our study aims to provide physicians and researchers with a historical perspective for the scientific progress of wheat allergy, and help clinicians effectively obtain useful articles that have a significant impact on the field of wheat allergy.
Asunto(s)
Bibliometría , Hipersensibilidad al Trigo , Hipersensibilidad al Trigo/inmunología , Hipersensibilidad al Trigo/epidemiología , Humanos , Triticum/inmunología , Triticum/efectos adversos , Gliadina/inmunología , Publicaciones Periódicas como Asunto/tendencias , Alérgenos/inmunologíaRESUMEN
Directed evolution is a pivotal strategy for new antibody discovery, which allowed the generation of high-affinity Fabs against gliadin from two antibody libraries in our previous studies. One of the libraries was exclusively derived from celiac patients' mRNA (immune library) while the other was obtained through a protein engineering approach (semi-immune library). Recent advances in high-throughput DNA sequencing techniques are revolutionizing research across genomics, epigenomics, and transcriptomics. In the present work, an Oxford Nanopore in-lab sequencing device was used to comprehensively characterize the composition of the constructed libraries, both at the beginning and throughout the phage-mediated selection processes against gliadin. A customized analysis pipeline was used to select high-quality reads, annotate chain distribution, perform sequence analysis, and conduct statistical comparisons between the different selection rounds. Some immunological attributes of the most representative phage variants after the selection process were also determined. Sequencing results revealed the successful transfer of the celiac immune response features to the immune library and the antibodies derived from it, suggesting the crucial role of these features in guiding the selection of high-affinity recombinant Fabs against gliadin. In summary, high-throughput DNA sequencing has improved our understanding of the selection processes aimed at generating molecular binders against gliadin.
Asunto(s)
Gliadina , Fragmentos Fab de Inmunoglobulinas , Secuenciación de Nanoporos , Biblioteca de Péptidos , Humanos , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/genética , Técnicas de Visualización de Superficie Celular/métodos , Gliadina/inmunología , Gliadina/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Fragmentos Fab de Inmunoglobulinas/genética , Fragmentos Fab de Inmunoglobulinas/inmunologíaRESUMEN
The long-term value of efficient antigen discovery includes gaining insights into the variety of potential cancer neoantigens, effective vaccines lacking adverse effects, and adaptive immune receptor (IR) targets for blocking adaptive IR-antigen interactions in autoimmunity. While the preceding goals have been partially addressed via big data approaches to HLA (human leukocyte antigen)-epitope binding, there has been little such progress in the big data setting for adaptive IR-epitope binding. This delay in progress for the latter is likely due to, among other things, the much more complicated adaptive IR repertoire in an individual compared to individual HLA alleles. Thus, results described here represent the application of an algorithm for efficient assessment of immunoglobulin heavy chain complementarity determining region-3 (IGH CDR3)-gliadin epitope interactions, with a focus on epitopes known to be associated with an immune response in celiac disease. The hydrophobic, chemical complementarity between celiac case IGH CDR3s and known celiac epitopes was found to be greater in comparison to the hydrophobic, chemical complementarity between the same celiac case IGH CDR3s and a series of control epitopes. Thus, the approaches indicated here likely offer guidance for the development of conveniently applied algorithms for antigen verification and discovery.
Asunto(s)
Enfermedad Celíaca , Regiones Determinantes de Complementariedad , Gliadina , Cadenas Pesadas de Inmunoglobulina , Humanos , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/genética , Regiones Determinantes de Complementariedad/genética , Regiones Determinantes de Complementariedad/inmunología , Regiones Determinantes de Complementariedad/química , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas Pesadas de Inmunoglobulina/inmunología , Gliadina/inmunología , Gliadina/química , Epítopos/inmunología , AlgoritmosRESUMEN
BACKGROUND: Wheat proteins can be divided into water/salt-soluble protein (albumin/globulin) and water/salt-insoluble protein (gliadins and glutenins (Glu)) according to solubility. Gliadins (Glia) are one of the major allergens in wheat. The inhibition of Glia antigenicity by conventional processing techniques was not satisfactory. RESULTS: In this study, free radical oxidation was used to induce covalent reactions. The effects of covalent reactions by high-intensity ultrasound (HIU) of different powers was compared. The enhancement of covalent grafting effectiveness between gliadin and (-)-epigallo-catechin 3-gallate (EGCG) was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry and Folin-Ciocalteu tests. HIU caused protein deconvolution and disrupted the intrastrand disulfide bonds that maintain the tertiary structure, causing a shift in the side chain structure, as proved by Fourier, fluorescence and Raman spectroscopic analysis. Comparatively, the antigenic response of the conjugates formed in the sonication environment was significantly weaker, while these conjugates were more readily hydrolyzed and less antigenic during simulated gastrointestinal fluid digestion. CONCLUSION: HIU-enhanced free radical oxidation caused further transformation of the spatial structure of Glia, which hid or destroyed the antigenic epitope, effectively inhibiting protein antigenicity. This study widened the application of polyphenol modification in the inhibition of wheat allergens. © 2024 Society of Chemical Industry.
Asunto(s)
Gliadina , Triticum , Gliadina/química , Gliadina/inmunología , Triticum/química , Triticum/inmunología , Oxidación-Reducción , Humanos , Alérgenos/química , Alérgenos/inmunología , UltrasonidoRESUMEN
BACKGROUND: Anti-endomysial antibodies (EMA) and anti-tissue transglutaminases (a-tTg) play a pivotal role in coeliac disease (CD) diagnosis. Deamidated anti-gliadin peptides (DGP) were added to the CD diagnostic workup. AIMS: We aimed to compare the diagnostic accuracies of ELISA-based (a-tTg/DGP) and immunofluorescence-ELISA-based strategies (EMA/a-tTg) for CD diagnosis. METHODS: From November 2020 to November 2022, we undertook an observational prospective study including consecutive adult patients with suspected CD. All subjects were tested for EMA, a-tTg and DGP IgA. An ROC curve was plotted to establish the best specificity cut-off of a-tTg and DGP levels, which would predict the presence of Marsh≥2 and Marsh=3. The diagnostic accuracies of a-tTg/DG and EMA/a-tTg were compared. RESULTS: The study included 275 CD patients. Histology showed Marsh=1 in 9.9%, Marsh=2 in 4.5%, and Marsh=3 in 85.6.%. The best cut-off value of a-tTg for predicting Marsh≥2 was 42 U/mL, while the best cut-off for predicting atrophy was 68.4 U/mL. The best cut-off value of DGP for predicting Marsh≥2 was 56 U/mL, while the best cut-off for predicting atrophy was 78 U/mL. A-tTg/EMA showed 97% sensitivity and 100% specificity, whereas a-tTg/DGP showed 94% sensitivity and 100% specificity. CONCLUSION: A-tTg/DGP is accurate for CD diagnosis and could reduce costs and operator-dependency of EMA. DGP, together with a-tTg, could replace EMA in CD diagnosis.
Asunto(s)
Enfermedad Celíaca , Ensayo de Inmunoadsorción Enzimática , Gliadina , Transglutaminasas , Humanos , Enfermedad Celíaca/diagnóstico , Gliadina/inmunología , Masculino , Femenino , Adulto , Ensayo de Inmunoadsorción Enzimática/métodos , Estudios Prospectivos , Transglutaminasas/inmunología , Persona de Mediana Edad , Sensibilidad y Especificidad , Autoanticuerpos/sangre , Curva ROC , Inmunoglobulina A/sangre , Anciano , Adulto JovenRESUMEN
BACKGROUND: A prior small-scale single center study suggested an association between celiac disease (CD)-type immunity and refractory temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). The present study addresses this putative association in a large, well-characterized group of drug-resistant epilepsy (DRE) patients. These patients were grouped based on the spectrum of CD and gluten sensitivity-associated antibodies. METHODS: In this cross-sectional study, 253 consecutive adult epilepsy patients (135 females, 118 males; age 16-76 years) were categorized into three groups: (i) CD-positive group with either prior diagnosis of CD or CD-specific TG2/EmA antibodies, (ii) AGA-positive group with antigliadin antibodies (AGA) but without CD, and (iii) CD/AGA-negative group without any gluten sensitivity-associated antibodies or CD. Clinical and immunological findings were then compared among the groups. RESULTS: TLE with HS was more common in the CD-positive group compared to CD/AGA-negative group (31.8% versus 11.9%, P = 0.019). Autoimmune disorders were more common in the AGA-positive group than in the CD/AGA-negative group (P = 0.025). Considering HS lateralization; left lateralization was more common in CD-positive group compared to CD/AGA-negative group (71.4% versus 25%, P = 0.030). TG6 seropositivity did not differ among the groups (P > 0.05). CONCLUSIONS: This study provides further evidence linking TLE with HS and CD-type autoimmunity suggesting that CD-type immune response to gluten can be one potential mechanism as a disease modifier leading to DRE and HS. Understanding these immunological factors is imperative for developing immunomodulatory or dietary treatments for DRE potentially preventing HS progression.
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Enfermedad Celíaca , Epilepsia Refractaria , Epilepsia del Lóbulo Temporal , Esclerosis del Hipocampo , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Autoanticuerpos/sangre , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/inmunología , Estudios Transversales , Epilepsia Refractaria/inmunología , Epilepsia Refractaria/etiología , Epilepsia del Lóbulo Temporal/inmunología , Epilepsia del Lóbulo Temporal/complicaciones , Gliadina/inmunología , Proteínas de Unión al GTP/inmunología , Esclerosis del Hipocampo/inmunología , Proteína Glutamina Gamma Glutamiltransferasa 2 , Transglutaminasas/inmunologíaRESUMEN
BACKGROUND: Low-dose oral food challenge (LD-OFC) is an approach to avoid complete elimination in high-risk patients with wheat allergy (WA). We examined the 3-year prognosis after LD-OFC among patients who passed and failed LD-OFC. METHODS: Children with immediate-type WA aged ≤6 years with a history of reaction to ≤390 mg of wheat protein underwent their first LD-OFC with 52 mg (baseline LD-OFC). After passing the LD-OFC, children stepped up to 390, 1300, and 5200 mg step-by-step every 3-6 months. After failing LD-OFC, children repeated LD-OFC every 6-12 months. We assessed wheat tolerance defined as consuming 5200 mg without symptoms for 3 years after baseline LD-OFC. RESULTS: The median age of 124 children was 2.4 years, and the wheat- and ω-5-gliadin-specific immunoglobulin E (IgE) levels (kUA/L) were 23.6 and 2.1, respectively. Upon baseline LD-OFC, 57% passed (LD-tolerant), whereas 43% failed (LD-reactive). Within 3 years, 38% of the LD-reactive group passed re-administered LD-OFC, and 70% of all participants avoided complete elimination. The percentage of the participants who became capable of consuming 390 mg (87% vs. 18%), 1300 mg (78% vs. 13%), and acquired tolerance (70% vs. 13%) was significantly higher in the LD-tolerant group than in the LD-reactive group (p < 0.001). Predictors of persistent WA in the LD-tolerant group were older age (adjusted odds ratio, 1.63), ω-5-gliadin-specific IgE level (1.62 per 10-fold increase), and other food allergies (1.94). CONCLUSIONS: LD-tolerant patients frequently acquired wheat tolerance within 3 years. Even if once positive, one-third could pass the re-administered LD-OFC within 3 years.
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Alérgenos , Inmunoglobulina E , Hipersensibilidad al Trigo , Humanos , Hipersensibilidad al Trigo/inmunología , Hipersensibilidad al Trigo/diagnóstico , Preescolar , Femenino , Masculino , Pronóstico , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Alérgenos/inmunología , Alérgenos/administración & dosificación , Lactante , Administración Oral , Niño , Tolerancia Inmunológica , Triticum/inmunología , Gliadina/inmunología , Antígenos de Plantas/inmunología , Antígenos de Plantas/administración & dosificaciónRESUMEN
Gastrointestinal health depends on the adaptive immune system tolerating the foreign proteins in food1,2. This tolerance is paradoxical because the immune system normally attacks foreign substances by generating inflammation. Here we addressed this conundrum by using a sensitive cell enrichment method to show that polyclonal CD4+ T cells responded to food peptides, including a natural one from gliadin, by proliferating weakly in secondary lymphoid organs of the gut-liver axis owing to the action of regulatory T cells. A few food-specific T cells then differentiated into T follicular helper cells that promoted a weak antibody response. Most cells in the expanded population, however, lacked canonical T helper lineage markers and fell into five subsets dominated by naive-like or T follicular helper-like anergic cells with limited capacity to form inflammatory T helper 1 cells. Eventually, many of the T helper lineage-negative cells became regulatory T cells themselves through an interleukin-2-dependent mechanism. Our results indicate that exposure to food antigens causes cognate CD4+ naive T cells to form a complex set of noncanonical hyporesponsive T helper cell subsets that lack the inflammatory functions needed to cause gut pathology and yet have the potential to produce regulatory T cells that may suppress it.
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Linfocitos T CD4-Positivos , Alimentos , Tolerancia Inmunológica , Alérgenos/inmunología , Formación de Anticuerpos , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , Proteínas en la Dieta/inmunología , Tracto Gastrointestinal/citología , Tracto Gastrointestinal/inmunología , Gliadina/inmunología , Tolerancia Inmunológica/inmunología , Inflamación , Interleucina-2/inmunología , Hígado/citología , Hígado/inmunología , Tejido Linfoide/citología , Tejido Linfoide/inmunología , Fragmentos de Péptidos/inmunología , Células T Auxiliares Foliculares/citología , Células T Auxiliares Foliculares/inmunología , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Células TH1/citología , Células TH1/inmunologíaRESUMEN
AIM: Deamidated gliadin peptide-IgG (DGP-IgG) antibody serology testing is widely utilised in screening for coeliac disease in Australia; however, it is used sparingly in Europe. The aim of this study was to assess the diagnostic value of a positive DGP-IgG in the setting of a negative tissue transglutaminase-IgA (tTG-IgA) for gastrointestinal pathology among paediatric patients. METHODS: We conducted a retrospective cohort study of all children with an elevated DGP-IgG in the setting of a negative tTG-IgA who underwent gastroscopy over a 48-month period (January 2015-December 2018) at a tertiary paediatric centre. They were identified utilising the electronic pathology database and demographic and clinical data were collected from electronic medical records. Patients who had previously been diagnosed with coeliac disease were on a gluten-free diet or over the age of 18 were excluded from the study. RESULTS: Twenty-six patients with an elevated DGP-IgG in the setting of a negative tTG-IgA underwent gastroscopy. Our study yielded a positive predictive value of 1/26 (3.9% CI 95% 0.7%, 18.9%) for the diagnosis of coeliac disease. Overall, there were 25 histopathological diagnoses including 1 diagnosis of coeliac disease among the total 26 patients who were positive DGP-IgG and negative tTG-IgA and underwent gastroscopy. CONCLUSIONS: Our findings suggest that an isolated positive DGP-IgG has a very low diagnostic yield for coeliac disease in children and may be indicative of other gastrointestinal pathology.
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Enfermedad Celíaca , Inmunoglobulina G , Autoanticuerpos , Enfermedad Celíaca/diagnóstico , Niño , Gliadina/inmunología , Humanos , Inmunoglobulina A , Inmunoglobulina G/análisis , Péptidos , Estudios Retrospectivos , Sensibilidad y Especificidad , TransglutaminasasRESUMEN
BACKGROUND: Autoimmune cerebellar ataxia (AICA) is a general term for diseases in which the cerebellum is damaged by an autoimmune mechanism. For the diagnosis of the AICA, anti-thyroid antibodies (anti-thyroid peroxidase antibody and anti-thyroglobulin antibody), anti-glutamic acid decarboxylase (GAD) antibodies, and anti-gliadin antibodies are measured. Immunotherapy is known to be effective for AICA, but some patients with effective immunotherapy lack autoantibodies associated with cerebellar ataxia. The purpose of this study was to clarify whether the effectiveness of immunotherapy in patients with suspected AICA could be predicted by anti-mouse cerebellar tissue-derived antigen antibody tests. METHODS: This study was conducted on 25 patients with idiopathic cerebellar ataxia (excluding multiple system atrophy, hereditary spinocerebellar degeneration, cancer-bearing patients, and patients taking phenytoin) who received immunotherapy from 2005 to 2016 at Tokyo Medical University Hachioji Medical Center. The patients were suspected of having AICA because they were positive for cerebellar ataxia-related autoantibodies (anti-thyroid antibody, anti-GAD antibody, anti-gliadin antibody, or anti-transglutaminase 6 antibody) or other autoantibodies. Antibodies that bind to mouse cerebellar tissue-derived antigens were defined as "anti-mouse cerebellar tissue-derived antigen antibodies" in this study, and their IgG-class antibodies were comprehensively measured using a slot blot. RESULTS: Anti-mouse cerebellar tissue-derived antigen antibody test results were correlated with immunotherapy efficacy. Furthermore, the combination of anti-mouse cerebellar tissue-derived antigen and anti-GAD antibody tests could predict the effectiveness of immunotherapy with 83% sensitivity and 100% specificity, while the combination of the anti-mouse cerebellar tissue-derived antigen, anti-GAD, and anti-gliadin (IgA class) antibody tests could predict the effectiveness of immunotherapy with 94% sensitivity and 86% specificity. CONCLUSION: Anti-mouse cerebellar tissue-derived antigen antibody tests could help to provide useful information for immunotherapy administration to patients with idiopathic cerebellar ataxia suspected to be AICA.
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Ataxia Cerebelosa , Inmunoterapia , Animales , Autoanticuerpos , Ataxia Cerebelosa/diagnóstico , Cerebelo , Gliadina/inmunología , Glutamato Descarboxilasa/inmunología , Humanos , Inmunoglobulina G , Factores InmunológicosRESUMEN
BACKGROUND: The general practice is to screen patients with autoimmune thyroid disease for celiac disease (CD); however, optimal timing for CD screening for patients with Graves'Disease (GD) has not been identified yet. The aim of the study was to show whether positive celiac antibodies persist after euthyroidism is achieved. MATERIALS AND METHODS: Serum samples were collected from 35 patients with GD (23 female and 12 male) who applied to the endocrine outpatient clinic. Patients and healthy controls were screened for CD with IgG and IgA antigliadin antibodies (IgG - AGA and IgA - AGA), IgA endomysial antibody (IgA-EMA) and IgA tissue transglutaminase antibody (IgA anti-tTG). These antibodies were reevaluated when patients were euthyroid under antithyroid therapy. Small intestine biopsy was offered to the patients who remained antibody positive after being euthyroid. RESULTS: Screening 35 patients with GD revealed positive results for IgA-AGA (n = 6/35, 17%), IgG-AGA (n = 9/35, 26%), IgA-EmA (n = 2/35, 6%) and IgA-tTG (n = 2/35, 6%). No patient had multiple antibodies positive. Selective IgA deficiency was not detected in patients and controls. When patients were euthyroid, baseline positive IgA-AGA, IgG-AGA, and IgA-EmA became negative, while positive anti-tTG persisted in two patients. Endoscopic duodenal biopsy showed a normal villi/crypts ratio in these patients. None of the controls had positive antibodies. CONCLUSION: Due to possibility of false seropositivity of celiac antibodies in patients with Graves' thyrotoxicosis, one should defer testing for CD until euthyroidism has been achieved.
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Enfermedad Celíaca , Enfermedad de Graves , Autoanticuerpos/sangre , Enfermedad Celíaca/sangre , Enfermedad Celíaca/diagnóstico , Femenino , Gliadina/inmunología , Humanos , Inmunoglobulina A/sangre , Masculino , Sensibilidad y Especificidad , Transglutaminasas/inmunologíaRESUMEN
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.
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Pan , Enfermedad Celíaca/inmunología , Dieta Sin Gluten , Gliadina/genética , Gliadina/inmunología , Glútenes/inmunología , Interferencia de ARN , Triticum/genética , Triticum/inmunología , Adulto , Enfermedad Celíaca/genética , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Interferencia de ARN/inmunología , Triticum/química , Adulto JovenRESUMEN
A hallmark of celiac disease is the gluten-dependent production of antibodies specific for deamidated gluten peptides (DGP) and the enzyme transglutaminase 2 (TG2). Both types of antibodies are believed to result from B cells receiving help from gluten-specific CD4+ T cells and differentiating into antibody-producing plasma cells. We have here studied the collaboration between DGP- and TG2-specific B cells with gluten-specific CD4+ T cells using transgenic mice expressing celiac patient-derived T-cell and B-cell receptors, as well as between B-cell transfectants and patient-derived gluten-specific T-cell clones. We show that multivalent TG2-gluten complexes are efficient antigens for both TG2-specific and DGP-specific B cells and allow both types of B cells to receive help from gluten-specific T cells of many different specificities.
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Enfermedad Celíaca/genética , Glútenes/genética , Proteína Glutamina Gamma Glutamiltransferasa 2/genética , Receptores de Antígenos de Linfocitos B/genética , Animales , Linfocitos B/inmunología , Linfocitos B/metabolismo , Linfocitos B/patología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/patología , Gliadina/genética , Gliadina/inmunología , Glútenes/inmunología , Humanos , Ratones , Ratones Transgénicos , Proteína Glutamina Gamma Glutamiltransferasa 2/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/patologíaRESUMEN
BACKGROUND: Test utilization for the diagnosis of celiac disease may affect the prevalence and incidence of the disease in Korea. We aimed to investigate the test utilization of serological biomarkers for celiac disease in Korea. METHODS: We retrospectively investigated the test utilization of tissue transglutaminase IgA, gliadin IgA and IgG, and endomysial IgA antibody (Ab) assays between January 2011 and June 2020. RESULTS: During a nine-year-and-six-month study period, overall 307,322,606 clinical tests were requested from different clinical settings, such as local clinics, hospitals, university hospitals, and tertiary medical centers. Among them, only 58 tissue transglutaminase IgA, 22 gliadin IgA, 12 gliadin IgG, and 16 endomysial IgA Ab tests were performed on 79 Korean patients. Among them, one patient had positive transglutaminase IgA Ab result (1.3%). CONCLUSION: Low prevalence and incidence of celiac disease in Korea may be due to an underutilization of diagnostic assays.
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Enfermedad Celíaca/diagnóstico , Pruebas Serológicas/estadística & datos numéricos , Enfermedad Celíaca/epidemiología , Pruebas Diagnósticas de Rutina , Gliadina/inmunología , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Proteína Glutamina Gamma Glutamiltransferasa 2/inmunología , República de Corea/epidemiología , Estudios RetrospectivosRESUMEN
Gluten-related disorders (GRDs) are a group of diseases that involve the activation of the immune system triggered by the ingestion of gluten, with a worldwide prevalence of 5%. Among them, Celiac disease (CeD) is a T-cell-mediated autoimmune disease causing a plethora of symptoms from diarrhea and malabsorption to lymphoma. Even though GRDs have been intensively studied, the environmental triggers promoting the diverse reactions to gluten proteins in susceptible individuals remain elusive. It has been proposed that pathogens could act as disease-causing environmental triggers of CeD by molecular mimicry mechanisms. Additionally, it could also be possible that unrecognized molecular, structural, and physical parallels between gluten and pathogens have a relevant role. Herein, we report sequence, structural and physical similarities of the two most relevant gluten peptides, the 33-mer and p31-43 gliadin peptides, with bacterial pathogens using bioinformatics going beyond the molecular mimicry hypothesis. First, a stringent BLASTp search using the two gliadin peptides identified high sequence similarity regions within pathogen-derived proteins, e.g., extracellular proteins from Streptococcus pneumoniae and Granulicatella sp. Second, molecular dynamics calculations of an updated α-2-gliadin model revealed close spatial localization and solvent-exposure of the 33-mer and p31-43 peptide, which was compared with the pathogen-related proteins by homology models and localization predictors. We found putative functions of the identified pathogen-derived sequence by identifying T-cell epitopes and SH3/WW-binding domains. Finally, shape and size parallels between the pathogens and the superstructures of gliadin peptides gave rise to novel hypotheses about activation of innate immunity and dysbiosis. Based on our structural findings and the similarities with the bacterial pathogens, evidence emerges that these pathologically relevant gluten-derived peptides could behave as non-replicating pathogens opening new research questions in the interface of innate immunity, microbiome, and food research.
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Enfermedad Celíaca/inmunología , Epítopos de Linfocito T , Gliadina/metabolismo , Glútenes/metabolismo , Imitación Molecular , Fragmentos de Péptidos/metabolismo , Carnobacteriaceae/metabolismo , Biología Computacional , Gliadina/química , Gliadina/inmunología , Glútenes/química , Glútenes/inmunología , Humanos , Fragmentos de Péptidos/química , Fragmentos de Péptidos/inmunología , Streptococcus pneumoniae/metabolismoRESUMEN
The safety and health effects for celiac people of a novel beverage (SOFB) developed from sprouted oat flour by fermentation with Lactobacillus plantarum was explored. In vitro reactivity against anti-gliadin antibodies (AGA) and antioxidant/anti-inflammatory potential of SOFB in RAW 264.7 macrophages and Caco-2 cells were evaluated. Immunoreactivity against AGA and antioxidant activity were not detected in SOFB, but it exhibited significant anti-inflammatory activity. The tolerability and impact of SOFB consumption for 6 months on nutritional status and intestinal microbiota composition were investigated in 10 celiac adults (five treated and five control). SOFB consumption did not adversely affect duodenal mucosa nor the total IgA or anti-tissue transglutaminase antibody (IgA-tTG) levels in celiac participants, but it significantly decreased total cholesterol levels at all sampling times and folic acid levels at the end of the study compared to the placebo beverage. SOFB administration also shifted gut microbiota, leading to a higher relative abundance of some beneficial bacteria including the genera Subdoligranulum, Ruminococcus and Lactobacillus in the SOFB group. This study provides supporting evidence of the safety of health benefits of a novel functional beverage produced from sprouted oat.
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Avena , Enfermedad Celíaca/dietoterapia , Alimentos Fermentados , Plantones , Animales , Antiinflamatorios , Anticuerpos/inmunología , Antioxidantes , Avena/inmunología , Células CACO-2 , Alimentos Funcionales , Microbioma Gastrointestinal , Gliadina/inmunología , Glútenes/análisis , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina A/inmunología , Lactobacillus plantarum/metabolismo , Ratones , Estado Nutricional , Células RAW 264.7RESUMEN
Coeliac disease (CD) is an autoimmune gastroenteropathy triggered by gliadin and gliadin-tissue transglutaminase (tTG) complexes. CD is one of the few autoimmune diseases with an accurate, non-invasive serological test. Anti-endomysial, anti-tTG and anti-deaminated gliadin peptides (DGP) antibodies are currently used for serological tests with tTG ELISAs being the superior test. Duodenal biopsy, although invasive, is the gold standard for CD diagnosis. HLA genotyping and flow cytometry can also be used as supplementary tests. The incidence of CD is rising globally although the reasons for this remain unclear. In addition, the true incidence of coeliac disease in African populations remains unknown although recent work suggests that South African populations express the alleles associated with this disease. This review examines the pathogenesis and diagnosis of coeliac disease and considers novel and innovative biomarkers in its diagnosis specifically in an African population.