Antibody responses to deamidated gliadin peptide show high specificity and parallel antibodies to tissue transglutaminase in developing coeliac disease

Abstract

SummaryCoeliac disease (CD) is an enteropathy induced in genetically susceptible individuals by gluten components, gliadin, hordein and secalin, polypeptides present in cereals such as wheat, barley and rye, respectively. Although the disease starts as intolerance to gliadins, antibodies to tissue transglutaminase (tTG) in the gut epithelium are characteristic of the disease. Whereas serum autoantibodies against tTG (tTGA) are highly specific for CD, antibodies to gliadin are less informative as they can also be detected in other enteropathies, and even in healthy individuals. However, it was shown recently that antibodies to certain gliadin peptides occur with high specificity in CD patient sera. We developed a solid phase lanthanide-based immunofluorometric assay for simultaneous detection of serum IgA and IgG antibodies to a synthetic peptide derived from gamma gliadin of wheat comprising amino acids 86-103. Three glutamine residues of this native 18-mer peptide were replaced by glutamic acids and the peptide was biotinylated. Sera from 87 individuals who had undergone duodenal biopsy and were diagnosed with CD and from 81 healthy individuals were analysed for the presence of both IgA and IgG anti-gliadin peptide antibodies. The performance of the peptide AGA assay was excellent, showing a specificity and sensitivity of 90% and 92% for IgA, and 98% and 75% for IgG, respectively. The corresponding values for conventional anti-gliadin antibody (AGA) enzyme-linked immunosorbent assay (ELISA) tests were 72% specificity and 87% sensitivity for IgA, and 64% specificity and 78% sensitivity for IgG. In a prospective study, almost all the tTGA-positive sera drawn from children who later developed CD were also positive for gliadin peptide antibodies.

Immunoreactivity of Antibodies Against Transglutaminase-Deamidated Gliadins in Adult Celiac Disease

“…The use of deamidated gliadin peptides-based ELISA (DGP-AGA) could be useful in patient diagnosis and follow-up [21]. Although there are no population-based studies on the employment of DGP-AGA, recent data from various tertiary clinics have shown DGP-AGA sensitivity and specificity comparable to tTGA [23][24][25] and anti-actin antibodies assays [26], higher than those of AGA assay [23,25]. In particular, Liu et al [27] demonstrated the usefulness of DGP-AGA in early diagnosis of children affected by CD, because antibodies against deamidated gliadin seem to appear before tTGA.…”

Is this really celiac disease? Pitfalls in diagnosis

“…The reason for the false positivity in these clinical conditions is not known, but it is possible that increased absorption of gluten or of its peptide fragments can be followed by a humoral immune response to the non-self antigen. The diagnostic accuracy of serum antibodies directed against deamidated gliadin seems to be higher [ 31 ], a recent fi nding that requires further confi rmation. The determination of IgG anti-tTG is useful in patients with selective IgA defi ciency (serum IgA < 5 mg/dL), but this condition should be kept separate from transient IgA defi ciency, a developmental and transient condition that is typical of infants and does not affect the possibility of an IgA-based antibody response.…”

Deamidated Gliadin Peptide Antibodies as a Routine Test for Celiac Disease

“…5 Antibodies to deamidated gliadin peptides (DGP-AGA) have recently been introduced into the wide spectrum of serologic tests for CD. [6][7][8][9][10][11][12] tTG selectively deamidates gliadin peptides by eliciting a strongly enhanced T-cell stimulatory activity, which plays a pivotal role in the development of the intestinal lesions. 13 DGP display more specific CD B-cell epitopes than the native nondeamidated peptides that are the target antigens of AGA.…”