Comparisons of Celiac Disease and Non-Celiac Gluten Sensitivity

Celiac disease (CD) and non-celiac gluten sensitivity (NCGS) are often confused or grouped together due to their commonalities. However, this is careless behavior because there are clinically significant differences between the two diseases. Similarities between them include varying degrees of damage or permeability in the lining of the small intestine, involvement of the innate immune system, alleviation of symptoms upon implementation of a gluten-free diet (GFD), and the possibility for complications if the pathology is not adequately treated. Despite these similarities, minor details such as the following make CD and NCGS worth differentiating: the question of gluten as the true trigger for NCGS, severity of villous atrophy present in only CD, psychiatric comorbidities present in NCGS, and possibility of a less restrictive treatment for NCGS using gluten detoxification

IL-1 regulates the IL-23 response to wheat gliadin, the etiologic agent of Celiac Disease

Celiac disease (CD) is an autoimmune disease prevalent in ~1% of the general population. CD is unique because both the major genetic (Human Leukocyte Antigen-DQ2/DQ8 alleles) and etiologic factors (dietary glutens) for susceptibility are known. While these alleles are responsible for the inappropriate T cell response that characterizes CD, they are not sufficient since most HLA-DQ2+/DQ8+ individuals exposed to glutens never develop disease. The reasons for this have not been explained; however our novel findings strongly advocate a role for interleukin-23 (IL-23) in the immunopathogenesis of CD. We demonstrate that wheat gliadin stimulates monocytes to produce significantly higher amounts of inflammatory cytokines IL-1b, IL-23, and tumor necrosis factor-a (TNFa) in CD patients compared to HLA-DQ2+ healthy individuals. Furthermore, we determine that IL-1 signalling is obligatory for production of IL-23, since IL-1b triggers IL-23 secretion in a dose-dependent manner and IL-1 receptor antagonist (IL-1ra) blocks IL-23 responses to gliadin. Our results suggest that gliadin activation of monocytes and the subsequent robust secretion of IL-1b and IL-23 initiate the immune response cascade that is manifest as CD, and reveal for the first time that the IL-1 system regulates production of IL-23. The discovery of IL-23 has highlighted the critical role of the innate immune response in autoimmunity and other inflammatory conditions. We anticipate that our novel findings will lead to the discovery of therapeutic targets for this disease and other inflammatory diseases mediated by IL-23

Emerging patterns of genetic overlap across autoimmune disorders.

Most of the recently identified autoimmunity loci are shared among multiple autoimmune diseases. The pattern of genetic association with autoimmune phenotypes varies, suggesting that certain subgroups of autoimmune diseases are likely to share etiological similarities and underlying mechanisms of disease. In this review, we summarize the major findings from recent studies that have sought to refine genotype-phenotype associations in autoimmune disease by identifying both shared and distinct autoimmunity loci. More specifically, we focus on information from recent genome-wide association studies of rheumatoid arthritis, ankylosing spondylitis, celiac disease, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes and inflammatory bowel disease. Additional work in this area is warranted given both the opportunity it provides to elucidate pathogenic mechanisms in autoimmunity and its potential to inform the development of improved diagnostic and therapeutic tools for this group on complex human disorders

Health related effects of wheat varieties

Summarises the different effects wheat digestion has on human healt

Efficient Replication of Over 180 Genetic Associations with Self-Reported Medical Data

While the cost and speed of generating genomic data have come down dramatically in recent years, the slow pace of collecting medical data for large cohorts continues to hamper genetic research. Here we evaluate a novel online framework for amassing large amounts of medical information in a recontactable cohort by assessing our ability to replicate genetic associations using these data. Using web-based questionnaires, we gathered self-reported data on 50 medical phenotypes from a generally unselected cohort of over 20,000 genotyped individuals. Of a list of genetic associations curated by NHGRI, we successfully replicated about 75% of the associations that we expected to (based on the number of cases in our cohort and reported odds ratios, and excluding a set of associations with contradictory published evidence). Altogether we replicated over 180 previously reported associations, including many for type 2 diabetes, prostate cancer, cholesterol levels, and multiple sclerosis. We found significant variation across categories of conditions in the percentage of expected associations that we were able to replicate, which may reflect systematic inflation of the effects in some initial reports, or differences across diseases in the likelihood of misdiagnosis or misreport. We also demonstrated that we could improve replication success by taking advantage of our recontactable cohort, offering more in-depth questions to refine self-reported diagnoses. Our data suggests that online collection of self-reported data in a recontactable cohort may be a viable method for both broad and deep phenotyping in large populations

HLA Class I or Class II and Disease Association: Catch the Difference if You Can

The association of autoimmune diseases with HLA has been known for many decades. To date, however, the underlying mechanisms have not been fully understood. The recently introduced genome-wide association studies (GWAS) have suggested that several genes converging in common pathways contribute to the genetic susceptibility in such disorders. Nevertheless, for most autoimmune/autoinflammatory diseases, the HLA genes are by far the strongest risk factors. The basis of some associations has now been elucidated, particularly in those cases in which exogenous factors are involved

Bezglutenski proizvodi namijenjeni osobama s celijakijom nisu dobar izvor folata i vitamina B12

The gluten-free diet, the only treatment in coeliac disease, can be nutritionally unbalanced and deficient in several nutrients. Gluten-free products contain much lower levels of B vitamins, especially lower folate concentrations than their gluten-containing counterparts. Folate intake is considered as a major dietary determinant of plasma homocysteine concentration in healthy population. Elevated homocysteine is an independent risk factor for cardiovascular disease and has been associated with osteoporotic fractures, which are an increased risk factor in coeliac disease. The aim of this study is to determine dietary folate intake and plasma homocysteine concentration as metabolic markers of suboptimal intake of folate and B12 in Croatian coeliac patients living on a gluten-free diet. Subjects were 52 coeliac patients (83 % female, age 35±13) adhering to a gluten-free diet. Blood samples were analyzed for plasma homocysteine, serum and red blood cell folate and serum B12. Quantitative food frequency questionnaire was used to measure dietary folate intake. Mean dietary folate intake was 206 mg of dietary folate equivalents (DFE), which was far below the national recommendation of 400 µg of DFE (or 200 μg of folic acid). Mean homocysteine was (9±2) μmol/L (range from 5.42 to 13.90 μmol/L), while elevated homocysteine concentrations (>10 μmol/L) were found in 34 % of subjects. In conclusion, coeliac patients adhering to gluten-free diet included in this study showed low folate intake and suboptimal folate and vitamin B12 status, possibly due to low folate content in gluten-free products. Therefore, folate fortification or enrichment of gluten-free products could be beneficial for coeliac patients and it would be of great interest for the food industry.Bezglutenska prehrana, jedini lijek za oboljele od celijakije, može biti neuravnotežena zbog nedostataka nekih hranjivih tvari. Bezglutenski proizvodi sadrže manju količinu vitamina B, osobito folata, nego slični proizvodi koji sadrže gluten. U zdravih osoba koncentracija homocisteina u plazmi uglavnom ovisi o prehrambenom unosu folata. Povećana vrijednost homocisteina u posljednje se vrijeme povezuje s osteoporozom koja je učestala u osoba s celijakijom. Svrha je ovoga rada utvrditi unos folata i status homocisteina kao metaboličkoga biljega suboptimalnog unosa folata i vitamina B12 u osoba s celijakijom na području Republike Hrvatske. U istraživanju su sudjelovale 52 osobe s celijakijom koje su na bezglutenskoj prehrani (83 % žena, dobi 35±13 godina). Analizom krvi utvrđena je koncentracija homocisteina, folata u serumu i eritrocitima te vitamina B12 u serumu. Kvantitativni je upitnik za procjenu unosa hrane i pića upotrijebljen radi utvrđivanja prehrambenog unosa folata. Prosječni je unos folata bio 206 µg ekvivalenata folata (eng. dietary folate equivalents-DFE), što je kudikamo manje od nacionalne preporuke koja navodi 400 µg DFE odnosno 200 µg folne kiseline. Prosječna vrijednost homocisteina iznosila je 9±2 µmol/L (raspon 5,42-13,90 µmol/L). Povećana vrijednost homocisteina (>10 µmol/L) utvrđena je u 34 % ispitanika. Može se zaključiti da osobe s celijakijom koje se pridržavaju bezglutenske prehrane, a sudjelovale su u ovom istraživanju, imaju mali unos folata i suboptimalan status folata i vitamina B12, vjerojatno zbog unosa folatom siromašnih bezglutenskih proizvoda. Stoga bi obogaćivanje ili dodatak folata u bezglutenske proizvode mogao povoljno utjecati na osobe s celijakijom, te predstavljati izazov prehrambenoj industriji

Production of the main celiac disease autoantigen by transient expression in Nicotiana benthamiana

Celiac Disease (CD) is a gluten sensitive enteropathy that remains widely undiagnosed and implementation of massive screening tests is needed to reduce the long term complications associated to untreated CD. The main CD autoantigen, human tissue transglutaminase (TG2), is a challenge for the different expression systems available since its cross-linking activity affects cellular processes. Plant-based transient expression systems can be an alternative for the production of this protein. In this work, a transient expression system for the production of human TG2 in Nicotiana benthamiana leaves was optimized and reactivity of plant-produced TG2 in CD screening test was evaluated. First, a subcellular targeting strategy was tested. Cytosolic, secretory, endoplasmic reticulum (C-terminal SEKDEL fusion) and vacuolar (C-terminal KISIA fusion) TG2 versions were transiently expressed in leaves and recombinant protein yields were measured. ER-TG2 and vac-TG2 levels were 9- to 16-fold higher than their cytosolic and secretory counterparts. As second strategy, TG2 variants were co-expressed with a hydrophobic elastin-like polymer (ELP) construct encoding for 36 repeats of the pentapeptide VPGXG in which the guest residue X were V and F in ratio 8:1. Protein bodies (PB) were induced by the ELP, with a consequent two-fold-increase in accumulation of both ER-TG2 and vac-TG2. Subsequently, ER-TG2 and vac-TG2 were produced and purified using immobilized metal ion affinity chromatography. Plant purified ER-TG2 and vac-TG2 were recognized by three anti-TG2 monoclonal antibodies that bind different epitopes proving that plant-produced antigen has immunochemical characteristics similar to those of human TG2. Lastly, an ELISA was performed with sera of CD patients and healthy controls. Both vac-TG2 and ER-TG2 were positively recognized by IgA of CD patients while they were not recognized by serum from non-celiac controls. These results confirmed the usefulness of plant-produced TG2 to develop screening assays. In conclusion, the combination of subcellular sorting strategy with co-expression with a PB inducing construct was sufficient to increase TG2 protein yields. This type of approach could be extended to other problematic proteins, highlighting the advantages of plant based production platforms.Fil: Marin Viegas, Vanesa Soledad. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; ArgentinaFil: Acevedo, Gonzalo Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bayardo, Mariela Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Petruccelli, Silvana. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; Argentin