The autoimmune condition, Celiac Disease (CeD), displays broad clinical symptoms due to gluten exposure. Its genetic association with DQ variants in the human leukocyte antigen (HLA) system has been recognised. Monocyte-derived mature dendritic cells (MoDCs) present gluten peptides through HLA-DQ and co-stimulatory molecules to T lymphocytes, eliciting a cytokine-rich microenvironment. Having access to CeD associated families prevalent in the Czech Republic, this study utilised an in vitro model to investigate their differential monocyte profile. The higher monocyte yields isolated from PBMCs of CeD patients versus control individuals also reflected the greater proportion of dendritic cells derived from these sources following lipopolysaccharide (LPS)/ peptic-tryptic-gliadin (PTG) fragment stimulation. Cell surface markers of CeD monocytes and MoDCs were subsequently profiled. This foremost study identified a novel bio-profile characterised by elevated CD64 and reduced CD33 levels, unique to CD14++ monocytes of CeD patients. Normalisation to LPS stimulation revealed the increased sensitivity of CeD-MoDCs to PTG, as shown by CD86 and HLA-DQ flow cytometric readouts. Enhanced CD86 and HLA-DQ expression in CeD-MoDCs were revealed by confocal microscopy. Analysis highlighted their dominance at the CeD-MoDC membrane in comparison to controls, reflective of superior antigen presentation ability. In conclusion, this investigative study deciphered the monocytes and MoDCs of CeD patients with the identification of a novel bio-profile marker of potential diagnostic value for clinical interpretation. Herein, the characterisation of CD86 and HLA-DQ as activators to stimulants, along with robust membrane assembly reflective of efficient antigen presentation, offers CeD targeted therapeutic avenues worth further exploration.
- MeSH
- Autoimmune Diseases immunology MeSH
- Biomarkers metabolism MeSH
- Cell Membrane metabolism MeSH
- Antigens, CD metabolism MeSH
- Celiac Disease epidemiology immunology MeSH
- T-Lymphocytes, Cytotoxic immunology MeSH
- Dendritic Cells immunology MeSH
- Adult MeSH
- Gliadin adverse effects MeSH
- HLA-DQ Antigens metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Lipopolysaccharides MeSH
- Adolescent MeSH
- Young Adult MeSH
- Monocytes metabolism MeSH
- Disease Susceptibility MeSH
- Antigen Presentation immunology MeSH
- Family MeSH
- Pedigree MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Celiakie je onemocněním autoimunního charakteru s geneticky podmíněnou vazbou HLA třídy II DQ2 nebo DQ8 charakterizovanou reakcemi střevních T buněk na proteiny pšeničného lepku v potravě. Unikátní peptidový fragment α2-gliadinu, gliadin-33mer, je považován za nejdůležitější imunogenní sekvenci v glutenu, peptid je zcela rezistentní na gastrointestinální peptidázy, a je zcela specifický pro prolaminy. Gliadin 33-mer je stimulátorem CD4-T buněk po deamidaci tkáňovou transglutaminázou. Jedinou ověřenou léčbou celiakie je celoživotní bezlepková dieta a v současné době se vyvíjí několik nových terapeutických přístupů. Enzymatické štěpení lepku pomocí glutenáz se zaměřením na cytotoxický gliadin 33-mer bylo ověřeno v řadě klinických studií. Detekce glutenových imunogenních peptidů, gliadin 33-meru, ve stolici a moči se stává novým neinvazivním biomarkerem a nabízí nový jednoduchý a objektivní způsob hodnocení příjmu lepku a ověření souladu s dodržováním bezlepkové diety u pacientů s celiakií. V diagnostice celiakie umožňuje spolehlivě ověřit non-responzibilní celiakii.
Celiac disease is an autoimmune disease with genetically determined HLA class II binding DQ2 or DQ8 characterized by intestinal T cell responses to wheat gluten proteins in the diet. The unique α2-gliadin peptide fragment, gliadin-33mer, is considered to be the most important immunogenic sequence in gluten, this peptide is completely resistant to gastrointestinal peptidases and is completely specific for prolamins. Gliadin 33-mer is a stimulator of CD4-T cells after deamidation by tissue transglutaminase. The only proven treatment for celiac disease is a lifelong gluten-free diet, and several new therapeutic approaches are currently being developed. The enzymatic cleavage of gluten by glutenases with a focus on the cytotoxic gliadin 33-mer has been verified in a number of clinical studies. Detection of gluten immunogenic peptides, gliadin 33-mer, in faeces and urine is becoming a new non-invasive biomarker and offers a new simple and objective way to assess gluten intake and verify compliance with a gluten-free diet in patients with celiac disease. In the diagnosis of celiac disease allows you to reliably verify non-responsive celiac disease.
- MeSH
- Treatment Adherence and Compliance MeSH
- Diet, Gluten-Free MeSH
- Biomarkers MeSH
- Celiac Disease * diagnosis diet therapy therapy MeSH
- Gliadin * analysis urine MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathy that is primarily treated with a gluten-free diet (GFD). Mucosal healing is the main target of the therapy. Currently, duodenal biopsy is the only way to evaluate mucosal healing, and non-invasive markers are challenging. Persistent elevation of anti-tissue transglutaminase antibodies (aTTG) is not an ideal predictor of persistent villous atrophy (VA). Data regarding prediction of atrophy using anti-deamidated gliadin peptide antibodies (aDGP) and abdominal ultrasonography are lacking. AIM: To evaluate the ability of aTTG, aDGP, small bowel ultrasonography, and clinical and laboratory parameters in predicting persistent VA determined using histology. METHODS: Patients with CD at least 1 year on a GFD and available follow-up duodenal biopsy, levels of aTTG and aDGP, and underwent small bowel ultrasonography were included in this retrospective cohort study. We evaluated the sensitivity, specificity, and positive and negative predictive values of aTTG, aDGP, small bowel ultrasonography, laboratory and clinical parameters to predict persistent VA. A receiver operating characteristic (ROC) curve analysis of antibody levels was used to calculate cut off values with the highest accuracy for atrophy prediction. RESULTS: Complete data were available for 82 patients who were followed up over a period of four years (2014-2018). Among patients included in the analysis, women (67, 81.7%) were predominant and the mean age at diagnosis was 33.8 years. Follow-up biopsy revealed persistent VA in 19 patients (23.2%). The sensitivity and specificity of aTTG using the manufacturer's diagnostic cutoff value to predict atrophy was 50% and 85.7%, respectively, while the sensitivity and specificity of aDGP (using the diagnostic cutoff value) was 77.8% and 75%, respectively. Calculation of an optimal cutoff value using ROC analysis (13.4 U/mL for aTTG IgA and 22.6 U/mL for aDGP IgA) increased the accuracy and reached 72.2% [95% confidence interval (CI): 46.5-90.3] sensitivity and 90% (95%CI: 79.5-96.2) specificity for aDGP IgA and 66.7% (95%CI: 41.0-86.7) sensitivity and 93.7% (95%CI: 84.5-98.2) specificity for aTTG IgA. The sensitivity and specificity of small bowel ultrasonography was 64.7% and 73.5%, respectively. A combination of serology with ultrasound imaging to predict persistent atrophy increased the positive predictive value and specificity to 88.9% and 98% for aTTG IgA and to 90.0% and 97.8% for aDGP IgA. Laboratory and clinical parameters had poor predictive values. CONCLUSION: The sensitivity, specificity, and negative predictive value of aTTG and aDGP for predicting persistent VA improved by calculating the best cutoff values. The combination of serology and experienced bowel ultrasound examination may achieve better accuracy for the detection of atrophy.
- MeSH
- Atrophy MeSH
- Autoantibodies * analysis MeSH
- Biopsy MeSH
- Celiac Disease * diagnosis pathology MeSH
- Gliadin MeSH
- Immunoglobulin A MeSH
- Humans MeSH
- Retrospective Studies MeSH
- Sensitivity and Specificity MeSH
- Transglutaminases MeSH
- Ultrasonography MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Pro vysokou prevalenci je celiakie jedním z nejdůležitějších onemocnění trávicího ústrojí. Pacientů je přibližně 1 % v populaci, a proto je vyhledávání tohoto onemocnění nezbytné. Prvním krokem v diagnostice celiakie je vyšetření protilátek proti tkáňové transglutamináze ve třídě A imunoglobulinů (anti‑TG‑IgA) a vyloučení deficitu IgA stanovením jeho celkové hodnoty. Tato kombinace dvou vyšetření je nejpřesnějším a nejrentabilnějším úvodním vyšetřením. Během prvního vyšetření není potřeba stanovovat protilátky proti endomysiu ve třídě IgA (EMA‑IgA) a protilátky proti deamidovanému gliadinu ve třídě G imunoglobulinů (anti‑DGP- IgG). Pokud má dítě dvakrát, tj. i ve druhém vzorku krve 10× vyšší hodnoty anti‑TG‑IgA a současně je také pozitivní EMA -IgA, je možno stanovit diagnózu celiakie bez následné biopsie. Děti, u kterých byla nalezena hodnota anti‑TG‑IgA nižší než 10násobek normální hodnoty, mají podstoupit střevní biopsii ke snížení rizika falešně pozitivní diagnózy. HLA vyšetření a přítomnost symptomů nejsou potřeba ke stanovení diagnózy celiakie bez biopsie.
For high prevalence celiac disease (CD) is one of the most important diseases of the digestive tract. Patients are approximately 1% in the population and therefore a search for this disease is necessary. The first step in the diagnosis of CD is to test antibodies to tissue transglutaminase in class A immunoglobulins (anti-TG-IgA) and to eliminate IgA deficiency by determining its total value. This combination of total IgA and anti-TG- IgA is the most accurate and cost-effective initial testing. At this time, there is no need to test antibodies to endomysium in class IgA (EMA-IgA) and antibodies to deamided gliadin in class G immunoglobulins (anti-DGP-IgG). If the child was twice found high values of the anti-TG-IgA >10 times the upper normal limit (ULN), i.e. even in the second blood sample and at the same time was also positive EMA-IgA, it is possible to make the diagnosis of CD without biopsy. Children who have been found to have an anti-TG-IgA value <10 times ULN should undergo an intestinal biopsy to reduce the risk of false positive diagnosis. HLA testing and presence of symptoms are not needed for a sérology based diagnosis without biopsy.
- MeSH
- Autoantibodies blood MeSH
- Biopsy standards MeSH
- Celiac Disease * diagnosis genetics immunology MeSH
- IgA Deficiency MeSH
- Child MeSH
- Duodenum pathology MeSH
- Gliadin immunology MeSH
- Glutens adverse effects MeSH
- HLA-DQ Antigens genetics MeSH
- Humans MeSH
- Practice Guidelines as Topic MeSH
- Transglutaminases immunology MeSH
- Check Tag
- Child MeSH
- Humans MeSH
Bread wheat (Triticum aestivum L.) is one of the most valuable cereal crops for human consumption. Its grain storage proteins define bread quality, though they may cause food intolerances or allergies in susceptible individuals. Herein, we discovered a diversity of grain proteins in three Ukrainian wheat cultivars: Sotnytsia, Panna (both modern selection), and Ukrainka (landrace). Firstly, proteins were isolated with a detergent-containing buffer that allowed extraction of various groups of storage proteins (glutenins, gliadins, globulins, and albumins); secondly, the proteome was profiled by the two-dimensional gel electrophoresis. Using multi-enzymatic digestion, we identified 49 differentially accumulated proteins. Parallel ultrahigh-performance liquid chromatography separation followed by direct mass spectrometry quantification complemented the results. Principal component analysis confirmed that differences among genotypes were a major source of variation. Non-gluten fraction better discriminated bread wheat cultivars. Various accumulation of clinically relevant plant proteins highlighted one of the modern genotypes as a promising donor for the breeding of hypoallergenic cereals.
- MeSH
- Electrophoresis, Gel, Two-Dimensional MeSH
- Albumins chemistry genetics metabolism MeSH
- Bread analysis MeSH
- Gliadin chemistry genetics MeSH
- Globulins chemistry genetics MeSH
- Glutens chemistry genetics MeSH
- Edible Grain chemistry genetics MeSH
- Humans MeSH
- Grain Proteins chemistry classification MeSH
- Proteome genetics MeSH
- Triticum chemistry genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
A therapeutic gluten-free diet often has nutritional limitations. Nutritional qualities such as high protein content, the presence of biologically active and beneficial substances (fiber, beta-glucans, polyunsaturated fatty acids, essential amino acids, antioxidants, vitamins, and minerals), and tolerance by the majority of celiac patients make oat popular for use in gluten-free diet. The health risk of long-time consumption of oat by celiac patients is a matter of debate. The introduction of oat into the diet is only recommended for celiac patients in remission. Furthermore, not every variety of oat is also appropriate for a gluten-free diet. The risk of sensitization and an adverse immunologically mediated reaction is a real threat in some celiac patients. Several unsolved issues still exist which include the following: (1) determination of the susceptibility markers for the subgroup of celiac patients who are at risk because they do not tolerate dietary oat, (2) identification of suitable varieties of oat and estimating the safe dose of oat for the diet, and (3) optimization of methods for detecting the gliadin contamination in raw oat used in a gluten-free diet.
- MeSH
- Diet, Gluten-Free * adverse effects MeSH
- Celiac Disease diagnosis diet therapy immunology MeSH
- Gliadin adverse effects immunology MeSH
- Risk Assessment MeSH
- Edible Grain * adverse effects classification immunology MeSH
- Clinical Decision-Making MeSH
- Food Contamination MeSH
- Humans MeSH
- Nutritive Value MeSH
- Avena * adverse effects classification immunology MeSH
- Patient Selection MeSH
- Recommended Dietary Allowances MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Biomarkers MeSH
- Celiac Disease * diagnosis classification MeSH
- Gliadin analysis urine MeSH
- Congresses as Topic MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- News MeSH
Antibodies to deamidated gliadin peptides (DGP-AGA) have newly been presented into the extensive variety of serologic examinations for celiac disease (CD). In compare with the modern AGA, DGP-AGA indicated a higher sensitivity and specificity for CD and simply identified by ELISA kits. Nevertheless, even though the very favorable outcomes, DGP-AGA are not yet regularly used in the serologic checkup for CD. An antibody approach could initiate development in the diagnostic precision of serology for CD screening.
The gluten ataxia is one of the commonest neurological manifestations of gluten-related disorders: prevalence was estimated at 15% amongst all ataxias and 40% of all idiopathic sporadic ataxias; its diagnosis should be confirmed by the prsence of anti-gliadin antibodies. Gluten ataxia is, by its management, very peculiar: few etiologies, among the large pannel of childhood ataxias, may respond to dietary treatments. We present an instructive case of gluten ataxia in a teenage girl.
- MeSH
- Ataxia * diagnosis diet therapy physiopathology MeSH
- Diet, Gluten-Free MeSH
- Child MeSH
- Gliadin immunology MeSH
- Glutens * adverse effects MeSH
- Humans MeSH
- Antibodies MeSH
- Diarrhea etiology MeSH
- Transglutaminases MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
