title: Specific nongluten proteins of wheat are novel target antigens in celiac disease humoral response.
abstract: While the antigenic specificity and pathogenic relevance of immunologic reactivity to gluten in celiac disease have been extensively researched, the immune response to nongluten proteins of wheat has not been characterized. We aimed to investigate the level and molecular specificity of antibody response to wheat nongluten proteins in celiac disease. Serum samples from patients and controls were screened for IgG and IgA antibody reactivity to a nongluten protein extract from the wheat cultivar Triticum aestivum Butte 86. Antibodies were further analyzed for reactivity to specific nongluten proteins by two-dimensional gel electrophoresis and immunoblotting. Immunoreactive molecules were identified by tandem mass spectrometry. Compared with healthy controls, patients exhibited significantly higher levels of antibody reactivity to nongluten proteins. The main immunoreactive nongluten antibody target proteins were identified as serpins, purinins, α-amylase/protease inhibitors, globulins, and farinins. Assessment of reactivity toward purified recombinant proteins further confirmed the presence of antibody response to specific antigens. The results demonstrate that, in addition to the well-recognized immune reaction to gluten, celiac disease is associated with a robust humoral response directed at a specific subset of the nongluten proteins of wheat.
authors.affiliation: Department of Medicine, Columbia University , New York, New York 10032, United States.
authors.forename: Sina
authors.initials: S
authors.lastname: Huebener
authors.forename: Charlene K
authors.initials: CK
authors.lastname: Tanaka
authors.forename: Melanie
authors.initials: M
authors.lastname: Uhde
authors.forename: John J
authors.initials: JJ
authors.lastname: Zone
authors.forename: William H
authors.initials: WH
authors.lastname: Vensel
authors.forename: Donald D
authors.initials: DD
authors.lastname: Kasarda
authors.forename: Leilani
authors.initials: L
authors.lastname: Beams
authors.forename: Chiara
authors.initials: C
authors.lastname: Briani
authors.forename: Peter H R
authors.initials: PH
authors.lastname: Green
authors.forename: Susan B
authors.initials: SB
authors.lastname: Altenbach
authors.forename: Armin
authors.initials: A
authors.lastname: Alaedini
mesh_terms: D000941:Antigens / Q000276:immunology*; D002446:Celiac Disease / Q000276:immunology*; D015180:Electrophoresis, Gel, Two-Dimensional; D000939:Epitopes; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D015151:Immunoblotting; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D010940:Plant Proteins / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D014908:Triticum / Q000378:metabolism*
chemical_list: D000941:Antigens; D000939:Epitopes; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010940:Plant Proteins
keywords: Celiac disease; antibody; farinin; globulin; immune response; purinin; serpin; α-amylase/protease inhibitor