Effect of Gliadin Stimulation on HLA-DQ2.5 Gene Expression in Macrophages from Adult Celiac Disease Patients

Macrophages play an important role in the pathogenesis of celiac disease (CD) because they are involved in both inflammatory reaction and antigen presentation. We analyzed the expression of CD-associated HLA-DQ2.5 risk alleles on macrophages isolated by two cohorts of adult patients, from the U.S. and Italy, at different stages of disease and with different genotypes. After isolating and differentiating macrophages from PBMC, we assessed the HLA genotype and quantified the HLA-DQ2.5 mRNAs by qPCR, before and after gliadin stimulation. The results confirmed the differences in expression between DQA1*05:01 and DQB1*02:01 predisposing alleles and the non-CD associated alleles, as previously shown on other types of APCs. The gliadin challenge confirmed the differentiation of macrophages toward a proinflammatory phenotype, but above all, it triggered an increase of DQA1*05:01 mRNA, as well as a decrease of the DQB1*02:01 transcript. Furthermore, we observed a decrease in the DRB1 genes expression and a downregulation of the CIITA transactivator. In conclusion, our findings provide new evidences on the non-coordinated regulation of celiac disease DQ2.5 risk genes and support the hypothesis that gliadin could interfere in the three-dimensional arrangement of chromatin at the HLA locus.

Evaluation of Thyroid Dysfunction in Adult Patients of Celiac Disease

OBJECTIVES: To assess free thyroxine (fT4), thyroid stimulating hormone (TSH), and anti thyroid peroxidase antibodies (anti TPO abs) in adult Celiac disease patients and non-celiac controls and to find out any statistically significant difference in their corresponding means between the two groups. METHODOLOGY: The study design was analytical cross sectional. Sixty adult patients of celiac disease (CD) and 30 apparently healthy non-celiac adults were included in the study. CD patients had earlier been diagnosed by elevated levels of serological evidence of elevated (greater than 15X ULN) anti tissue transglutaminase (TTG) (IgA class) antibodies. CD was ruled out in the control group by normal levels of the antibodies. TSH, fT4 and anti TPO abs were obtained from all individuals of CD patient and control groups. RESULTS: Mean age of Celiac disease in patients was 23.85±5.43 years. Mean age of individuals in the control group was 24.26±5.55 years. Statistically significant difference in mean TSH and anti-TPO abs levels between the CD patient group and control group (p values of 0.03 and 0.038, respectively) was present. No statistically significant difference was seen between mean fT4 of patients and control group (p=0.74). Subclinical and overt hypothyroidism was present in 10% and 5% of CD patients, while anti TPO abs was positive in 16.6% of CD patients. CONCLUSION: There is a considerably high prevalence of subclinical and overt hypothyroidism as well as serological evidence of thyroid dysfunction in adult patients of CD.

Association between systemic immune inflammation index and newly diagnosed adult celiac disease

Objectives The systemic immune inflammation index (SII) is a novel biomarker based on platelet, neutrophil and lymphocyte counts. SII serum levels have diagnostic, prognostic degrees and correlations with various immune, inflammatory diseases. Celiac disease (CD) is an immune-mediated chronic enteropathy with inflammatory situations. Here we aimed to evaluate clinical significance of SII and to compare SII with other inflammatory markers in CD. Methods 161 pathologically confirmed CD and 75 dyspeptic patients were enrolled. Hemogram, biochemical markers, SII, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), mean platelet volume-to-platelet ratio (MPR) and monocyte-to-high density lipoprotein cholesterol ratio (MHR) were evaluated. Results There was a statistically significant difference between groups for SII (p<0.001). SII was statistically correlated with and superior to inflammatory markers in relation with CD. There were also statistically significant differences between groups for hsCRP, PLR, NLR, MPR, haemoglobin, platelet count, platelet volume distribution width, plateletcrit, ferritin, total cholesterol and HDL cholesterol (p=0.034; 0.015; 0.032; <0.001; <0.001; <0.001; 0.030; 0.001; <0.001; <0.001; 0.048, respectively). Correlations between SII and NLR, PLR, MHR, hsCRP were statistically significant (p≤0.001; <0.001; 0.033; 0.030, respectively). ROC analysis was used to determine the optimal cut-off value for CD by SII. A baseline SII level >560.0 was associated with CD with 64% specificity, 78% sensitivity (p<0.001). Conclusions To the best of our knowledge, this is the first study analyzed the diagnostic value of SII in CD. SII may serve as a beneficial marker for the diagnosis of inflammatory state superior to that of hsCRP, PLR, NLR, MHR, MPR and WBC.

Modern understanding of adult celiac disease

The article presents a modern view of celiac disease within the framework of the classification concept of gluten- associated disorders. The prevalence of the disease, the modern model of the etiopathogenesis of celiac disease, clinical manifestations, and the possibilities of differential diagnosis are discussed. According to the European guidelines, a strategy for monitoring outpatients with celiac disease is presented, based on baseline characteristics of the disease, regular doctor- patient interaction, and prevention of gluten- associated disorders.

Salivary Microbiome in Pediatric and Adult Celiac Disease

The human salivary microbiota includes hundreds of bacterial species. Alterations in gut microbiota have been explored in Celiac Disease (CD), but fewer studies investigated the characteristics of salivary microbiome in these patients, despite the potential implications in its pathogenesis. Indeed, some recent studies suggested that the partial digestion of gluten proteins by some bacteria may affect the array of gluten peptides reaching the gut and the way by which those are presented to the intestinal immune system. The available clinical studies investigating the salivary microbiota in children and adults, are insufficient to make any reliable conclusion, even though some bacterial species/phyla differences have been reported between celiac patients and controls. However, the salivary microbiome could correlate better with the duodenal microbiota, than the fecal one. Therefore, further clinical studies on salivary microbiome by different and independent research groups and including different populations, are advisable in order to explore the usefulness of the salivary microbiome analysis and understand some aspects of CD pathogenesis with potential clinical and practical implications.

Comparative Study of Salivary, Duodenal, and Fecal Microbiota Composition Across Adult Celiac Disease

Background: Growing evidence suggests that an altered microbiota composition contributes to the pathogenesis and clinical features in celiac disease (CD). We performed a comparative analysis of the gut microbiota in adulthood CD to evaluate whether: (i) dysbiosis anticipates mucosal lesions, (ii) gluten-free diet restores eubiosis, (iii) refractory CD has a peculiar microbial signature, and (iv) salivary and fecal communities overlap the mucosal one. Methods: This is a cross-sectional study where a total of 52 CD patients, including 13 active CD, 29 treated CD, 4 refractory CD, and 6 potential CD, were enrolled in a tertiary center together with 31 controls. A 16S rRNA-based amplicon metagenomics approach was applied to determine the microbiota structure and composition of salivary, duodenal mucosa, and stool samples, followed by appropriate bioinformatic analyses. Results: A reduction of both α- and β-diversity in CD, already evident in the potential form and achieving nadir in refractory CD, was evident. Taxonomically, mucosa displayed a significant abundance of Proteobacteria and an expansion of Neisseria, especially in active patients, while treated celiacs showed an intermediate profile between active disease and controls. The saliva community mirrored the mucosal one better than stool. Conclusion: Expansion of pathobiontic species anticipates villous atrophy and achieves the maximal divergence from controls in refractory CD. Gluten-free diet results in incomplete recovery. The overlapping results between mucosal and salivary samples indicate the use of saliva as a diagnostic fluid.

Neurological disorder in celiac patient after third molars extraction: is there a relation?

Celiac disease is an immune-mediated gluten-dependent systemic disorder characterized by a specific profile associated with small intestinal lesion. Some of the classical symptoms observed in patients with this condition are nutrient malabsorption, diarrhea, abdominal pain, fatigue and, more recently, neurological symptoms were associated with the disease. Therefore, the objective is to inform an unusual case of a patient with celiac disease that developed severe permanent paresthesia in the superior and inferior gingiva, tongue and palate after tooth extraction e to discuss the relation between both things.Descriptors: Nervous System Disease; Celiac Disease; Molar, Third.ReferencesFasano A, Catassi C. Clinical practice. Celiac disease. N Engl J Med 2012; 367(25):2419-26.Guandalini S, Assiri A. Celiac disease: a review. JAMA Pediatr. 2014;168(3):272-78.de Carvalho FK, de Queiroz AM, Bezerra da Silva RA, Sawamura R, Bachmann L, Bezerra da Silva LA et al. Oral aspects in celiac disease children: clinical and dental enamel chemical evaluation. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015,119(6):636-43.Sanders DS, Patel D, Stephenson TJ, Ward AM, McCloskey EV, Hadjivassiliou M et al. A primary care cross-sectional study of undiagnosed adult celiac disease. Eur J Gastroenterol Hepatol 2003;15(4):407-13.Briani C, Zara G, Alaedini A, Grassivaro F, Ruggero S, Toffanin E et al. Neurological complications of coeliac disease and autoimmune mechanisms: a prospective study. J Neuroimmunol 2008;195(1-2):171-75.Bataineh AB. Sensory nerve impairment following mandibular third molar surgery. J Oral Maxillofac Surg. 2001;59(9):1012-17.Green PH. The many faces of celiac disease: clinical presentation on celiac disease in the adult population. Gastroenterology. 2005;128(4Suppl1): S74-8.Muller AF, Donnelly MT, Smith CM, et al. Neurological complications of celiac disease: a rare but continuing problem. Am J Gastroenterol. 1996; 91(7):1430-35.Chin RL, Snader HW, Brannagan TH, Green PH, Hays AP, Alaedini A et al. Celiac neuropathy. Neurology. 2003;60(10):1581-85.Alaedini A, Green PH, Sander HW, Hays AP, Gamboa AT, Fasano A et al. Ganglioside reactive antibodies in the neuropathy associated with celiac disease. J Neuroimmunol. 2002; 127(1-2):145-48.Oh SJ, Melo AC, Lee DK, Cichy SW, Kim DS, Demerci M et al. Large fiber neuropathy in distal sensory neuropathy with normal routine nerve conduction. Neurology.2001;56(11):1570-72.