Celiac disease: antibody recognition against native and selectively deamidated gliadin peptides.
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 alpha-type gliadin; and peptide-2, with residues 134-153 of gamma-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.
Aleanzi
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Cátedra de Bioquímica Básica de Macromoléculas, INTEBIO, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Pje. el Pozo. CC 242, 3000 Santa Fe, Argentina. maleanzi@fbcb.unl.edu.ar
Demonte
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AM
Esper
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Garcilazo
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Waggener
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D000293:Adolescent; D000595:Amino Acid Sequence; D002446:Celiac Disease / Q000178:diet therapy / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D019204:GTP-Binding Proteins / Q000276:immunology; D005903:Gliadin / Q000737:chemistry / Q000276:immunology*; D005983:Glutens / Q000008:administration & dosage; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology
D000939:Epitopes; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010446:Peptide Fragments; D005983:Glutens; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins