Location: Crop Improvement and Genetics ResearchTitle: Specific nongluten proteins of wheat are novel target antigens in celiac disease humoral response
|HUEBENER, S - Columbia University - New York|
|UHDE, M - Columbia University - New York|
|ZONE, J - University Of Utah|
|BEAMS, L - Columbia University - New York|
|BRIANI, C - Universita Di Padova|
|GREEN, P - Columbia University - New York|
|ALAEDINI, A - Columbia University - New York|
Submitted to: Journal of Proteome Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/20/2014
Publication Date: 10/20/2014
Citation: Moeller, S., Tanaka, C.K., Green, P.H., Zone, J.J., Vensel, W.H., Kasarda, D.D., Briani, C., Altenbach, S.B., Alaedini, A. 2014. Specific nongluten proteins of wheat are novel target antigens in celiac disease humoral response. Journal of Proteome Research. 14:503-511.
Interpretive Summary: It is well-known that celiac disease is triggered by the ingestion of gluten proteins from wheat and related cereals. However, the roles of other wheat proteins in the pathogenesis of celiac disease and the related condition dermatitis herpetiformis have not been investigated. As a result, two-dimensional immunoblotting was used to identify non-gluten proteins from wheat flour that reacted with sera from seventy individuals with celiac disease or dermatitis herpetiformis. Several types of proteins showed strong reactions with the patient sera, including serpins, '-amylase/protease inhibitors, purinins, globulins and farinins. These proteins did not react with sera from control patients. The data suggest that certain non-gluten proteins may also be important in the pathogenesis of celiac disease and dermatitis herpetiformis and therefore warrant further study.
Technical Abstract: Background: Celiac disease is an immune-mediated enteropathy that is generally understood to be triggered by the ingestion of gluten proteins of wheat and related cereals. The skin manifestation of the condition is known as dermatitis herpetiformis. Antibody response to native and deamidated sequences of gluten proteins is one of the hallmarks of celiac disease. While the target specificity and pathogenic relevance of immunologic reactivity to gluten have been extensively researched, little is known about the existence or molecular specificity of immune response to non-gluten proteins of wheat in celiac disease. Methods: Study participants included patients with celiac disease or dermatitis herpetiformis (n=70) and healthy controls (n=50). Serum samples were tested by ELISA for IgG and IgA antibodies to a total extract of non-gluten proteins from the extensively characterized wheat cultivar Triticum aestivum 'Butte 86'. Sera with the highest detected antibody levels were further analyzed by two-dimensional immunoblotting for reactivity to separated proteins. Identities of immunoreactive molecules were determined by software-assisted comparison of blots to a generated proteomic map in which ‘Butte 86’ wheat proteins had been identified by mass spectrometry. Results: Patients with celiac disease or dermatitis herpetiformis had significantly higher IgG and IgA levels of antibody to the non-gluten protein extract compared with healthy controls, as determined by ELISA. Two-dimensional immunoblotting confirmed the presence of antibody reactivity to specific non-gluten proteins in the affected patients. Patient antibodies were found to be most frequently reactive towards a serpin protein. Other highly immunoreactive proteins included a-amylase/protease inhibitors, purinins, globulins, and farinins. Conclusion: In addition to the well-recognized immune reaction to gluten proteins, celiac disease is associated with a robust humoral response directed at specific non-gluten proteins of wheat. Immune reactivity to the identified non-gluten antigens may have implications for the pathogenic mechanism and treatment of celiac disease.