Specificity of Tissue Transglutaminase Explains Cereal Toxicity in Celiac Disease

Celiac disease is caused by a selective lack of T cell tolerance for gluten. It is known that the enzyme tissue transglutaminase (tTG) is involved in the generation of T cell stimulatory gluten peptides through deamidation of glutamine, the most abundant amino acid in gluten. Only particular glutamine residues, however, are modified by tTG. Here we provide evidence that the spacing between glutamine and proline, the second most abundant amino acid in gluten, plays an essential role in the specificity of deamidation. On the basis of this, algorithms were designed and used to successfully predict novel T cell stimulatory peptides in gluten. Strikingly, these algorithms identified many similar peptides in the gluten-like hordeins from barley and secalins from rye but not in the avenins from oats. The avenins contain significantly lower percentages of proline residues, which offers a likely explanation for the lack of toxicity of oats. Thus, the unique amino acid composition of gluten and related proteins in barley and rye favors the generation of toxic T cell stimulatory gluten peptides by tTG. This provides a rationale for the observation that celiac disease patients are intolerant to these cereal proteins but not to other common food proteins

Small intestinal T cells of celiac disease patients recognize a natural pepsin fragment of gliadin

Celiac disease is a common severe intestinal disease resulting from intolerance to dietary wheat gluten and related proteins. The large majority of patients expresses the HLA-DQ2 and/or DQ8 molecules, and gluten-specific HLA-DQ-restricted T cells have been found at the site of the lesion in the gut. The nature of peptides that are recognized by such T cells, however, has been unclear so far. We now report the identification of a gliadin-derived epitope that dominantly is recognized by intestinal gluten-specific HLA-DQ8-restricted T cells. The characterization of such epitopes is a key step toward the development of strategies to interfere in mechanisms involved in the pathogenesis of celiac disease

A longitudinal study on determinants of HPV vaccination uptake in parents/guardians from different ethnic backgrounds in Amsterdam, the Netherlands

Human papillomavirus (HPV) vaccination coverage in the Netherlands is low (~60%) compared to other childhood vaccinations (>90%), and even lower among ethnic minorities. The aim of this study was to explore the possible impact of ethnicity on the determinants of both HPV vaccination intention and HPV vaccination uptake among parents/guardians having a daughter that is invited for the HPV vaccination. In February 2014, parents/guardians living in Amsterdam were invited to complete a questionnaire about social-psychological determinants of their decision making process regarding the HPV vaccination of their daughter and socio-demographic characteristics. This questionnaire was sent approximately one month before the daughter was scheduled to receive her first HPV vaccine dose. Their daughters' HPV vaccination status was retrieved from the national vaccination database. We distinguished four ethnic groups: Dutch (NL), Surinamese, Netherlands Antillean, and Aruban (SNA), Middle-Eastern and North-African (MENA), and Other. To assess the impact of determinants on both intention and uptake, linear and logistic regression analyses were used respectively. Missing data were imputed using multiple imputation by chained equation. In total 1,309 parents/guardians participated (33% participation rate). In all groups we found the mothers' intention to be the strongest predictor of their daughters' HPV vaccination uptake. Explained variance of uptake was highest in the NL-group (pseudo-R(2):0.56) and lower in the other ethnic groups (pseudo-R(2) varied between 0.23 and 0.29). The lower explained variance can be attributed to the relative large proportion of participants with a positive intention that finally did not go for vaccination in the SNA-group (11%) and MENA-group (30%). Explained variance (R(2)) of intention varied between 0.66 and 0.77 across ethnic groups, and was best explained by the proximal social-psychological determinants. The strength of association of these determinants with both intention and uptake were largely similar across ethnic groups. We conclude that the same determinants should be targeted in the different ethnic groups, although the mode of delivery of the intervention needs to be tailored to the different cultural backgrounds. Further research is needed to explain the observed discrepancy between intention and uptake, especially among parents/guardians in the non-Dutch group

Additional file 1: Table S1. of A longitudinal study on determinants of HPV vaccination uptake in parents/guardians from different ethnic backgrounds in Amsterdam, the Netherlands

Overview of social-psychological scale measures used in the questionnaire for HPV vaccine acceptability among parents/guardians in Amsterdam, the Netherlands, 2014. Table S2. Response rate stratified by country of birth of the mother of the invited girl, HPV vaccination acceptability study in Amsterdam, the Netherlands, 2014. Table S3. HPV vaccination uptake: bivariable logistic regression analyses of social-psychological, socio-demographic and other factors. HPV vaccination acceptability study in Amsterdam, the Netherlands, 2014. Table S4. HPV vaccination intention: bivariable linear regression analyses of social-psychological, socio-demographic and other factors, HPV vaccination acceptability study in Amsterdam, the Netherlands, 2014. Table S5. HPV vaccination uptake: multivariable logistic regression analyses of complete cases of social-psychological, socio-demographic and other factors. HPV vaccination acceptability study among parents/guardians, in Amsterdam, the Netherlands, 2014. Table S6. Complete case analyses: Odds ratios for the association between key determinants and vaccination uptake among Dutch parents/guardians, and interaction between ethnic group and these determinants. HPV vaccination acceptability study among parents/guardians, in Amsterdam, the Netherlands, 2014. Table S7. HPV vaccination intention: multivariable linear regression analyses of complete cases of socio-demographic, social-psychological and other factors. HPV vaccination acceptability study among parents/guardians, in Amsterdam, the Netherlands, 2014. Table S8. Complete case analyses: Regression coefficient for the association between key determinants and vaccination intention among Dutch parents/guardians, and interaction between ethnic group and these determinants. HPV vaccination acceptability study among parents/guardians, in Amsterdam, the Netherlands, 2014. Figure S1. Schematic representation of key dates and periods: HPV vaccination acceptability study, Amsterdam 2014 The vertical line indicates the time. Figure S2. Flow diagram of the recruitment and response of parents/guardians and their daughters of the HPV vaccination acceptability study, Amsterdam 2014. Figure S3. Proportion of girls that received two HPV vaccine doses by neighborhood in the health district of the Public Health Service of Amsterdam. (DOCX 389 kb