Prevalence of coexisting autoimmune thyroidal diseases in coeliac disease is decreasing.

Background: Coeliac disease (CD) is associated with an increased risk of other immune-mediated conditions. : To investigate the prevalence of coexistent immune-mediated diseases in CD patients, and changes in the prevalence of autoimmune thyroidal diseases over the last 50 years.

Methods: Medical record data were collected retrospectively from 749 CD patients in Ireland.

Protein kinase C delta is a substrate of tissue transglutaminase and a novel autoantigen in coeliac disease.

Post-translational modification of proteins by deamidation or transamidation by tissue transglutaminase (tTG) has been suggested as a possible mechanism for the development of autoimmunity. Sequence analysis of protein kinase C delta (PKCδ) identified an amino acid motif that suggested the possibility that PKCδ was a glutamine substrate of tTG and MALDI-TOF analysis of synthesised peptides from PKCδ proved that this was the case. Polymerisation experiments using recombinant tTG and biotinylated hexapeptide substrate incorporation assays demonstrated that PKCδ is a substrate for tTG-mediated transamidation.

Coeliac disease autoantibodies mediate significant inhibition of tissue transglutaminase.

The detection of antibodies directed against tissue transglutaminase (tTG) in serum is a sensitive and specific test for suspected coeliac disease. tTG is a ubiquitous, multifunctional enzyme that has been implicated in many important physiological processes as well as the site-specific deamidation of glutamine residues in gluten-derived peptides. This modification of gluten peptides facilitates their binding to HLA-DQ2, which results in amplification of the T-cell response to gluten.

Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine kinase.

Toll-like receptors (TLRs) are a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense. TLR7 and TLR8 sense single-stranded RNA from viruses or host ribonucleoproteins and synthetic imidazoquinolines such as R848, whereas TLR9 senses unmethylated CpG motifs in viral and bacterial DNA and in host DNA. Here we report the endogenous interaction between Brutons's tyrosine kinase (Btk) and human TLR8 and TLR9 in the monocytic cell line THP1.

A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21.

We tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls. Outside the HLA region, the most significant finding (rs13119723; P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block.

Mutagenesis of the catalytic triad of tissue transglutaminase abrogates coeliac disease serum IgA autoantibody binding.

Background And Aims: Tissue transglutaminase (tTG) is an autoantigen in coeliac disease and the related disorder, dermatitis herpetiformis. The detection of autoantibodies directed against tTG is a highly specific marker of coeliac disease; however, it is unclear if there is a role for these autoantibodies in the disease process. The aim of this study was to investigate whether the catalytic triad of tTG is targeted by coeliac disease autoantibodies.