Celiac Disease

Abstract

Background: Selective deamidation of glutamine residues by tissue transglutaminase (tTG) turns gliadin peptides into stronger activators of T cells from celiac disease (CD) patients. We examined the possibility that these modified peptides could be more specific epitopes for circulating antibodies than are native peptides. Methods: Two native synthetic peptides and their respective modified sequences were used as antigens for ELISA assays: peptide-1, with residues 56–75 of α-type gliadin; and peptide-2, with residues 134–153 of γ-type gliadin. We examined 40 CD patients [31 not being treated with a gluten-free diet (GFD) and 9 being treated with a GFD] and 30 non-CD patients. Results: An enhanced response against deamidated peptides was observed in 4 (IgA) and 22 (IgG) of 31 untreated CD patients for peptide-1 and in 25 (IgA) and 29 (IgG) patients for peptide-2. Higher anti-gliadin antibody and anti-tTG IgA concentrations correlated with increased IgA reactivity to modified peptides. Among the nine treated CD patients, eight also displayed an improved IgG signal for the deamidated sequence. Deamidation of peptides did not increase the reactivity of non-CD sera. Conclusions: Selective deamidation specifically increases circulating antibody recognition of gliadin peptides in CD patients. This suggests that deamidated gliadin peptides are more specific CD B-cell epitopes than native peptides; this finding may be relevant for designing improved diagnostic tests.

Natural History of Antibodies to Deamidated Gliadin Peptides and Transglutaminase in Early Childhood Celiac Disease

“…It is intriguing to consider how antibodies to DGP could be specific to celiac disease. Two possible explanations have been offered as to why antibodies to deamidated gliadin epitopes exist in celiac patients, as cited by Aleanzi et al (16). Given that T cell reactivity is enhanced by deamidated (as opposed to native) gliadin sequences, B cell activation may be more robust to previously deamidated peptides.…”

Use of Deamidated Gliadin Peptide Antibodies to Monitor Diet Compliance in Childhood Celiac Disease

“…Dietary gluten is partially digested into gliadin peptides that pass through the small bowel epithelium and are bound to the human leukocyte antigen HLA-DQ2 or DQ8 on the surface of antigen-presenting cells. This binding is strongly enhanced by deamidation, catalyzed by anti-tTG, thus resulting in a greatly enhanced T-cell (9,10) and antibody response (11). Recent studies have shown that deamidation increases binding of antibodies to gliadin in the sera of patients with CD but not of controls (11)(12)(13)(14).…”

Novel Screening Assay Performance in Pediatric Celiac Disease and Adult Dermatitis Herpetiformis

“…In several studies, selective deamidation of gliadin increased performance for both IgA and IgG in adult and pediatric patients with CD (11,12). In fact, the sensitivity and specificity of EIA using synthetic deamidated gliadin peptides (DGP) is considerably superior to whole gliadin (11,13). Studies have shown IgA anti-DGP to have up to 97% concordance with IgA anti-tTG and EMA with sensitivities exceeding 92% and specificities more than or equal to 99% (12,14,15).…”

“…However, the reported sensitivity and specificity for IgA anti-AGA in CD vary widely (9). In several studies, selective deamidation of gliadin increased performance for both IgA and IgG in adult and pediatric patients with CD (11,12). In fact, the sensitivity and specificity of EIA using synthetic deamidated gliadin peptides (DGP) is considerably superior to whole gliadin (11,13).…”