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Specific nongluten proteins of wheat are novel target antigens in celiac disease humoral response.

Huebener S, Tanaka CK, Uhde M, Zone JJ, Vensel WH, Kasarda DD, Beams L, Briani C, Green PH, Altenbach SB, Alaedini A - J. Proteome Res. (2014)

Bottom Line: Immunoreactive molecules were identified by tandem mass spectrometry.The main immunoreactive nongluten antibody target proteins were identified as serpins, purinins, α-amylase/protease inhibitors, globulins, and farinins.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Columbia University , New York, New York 10032, United States.

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.

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Antibody reactivity to gluten and to nongluten proteins of wheat.(A) Gel electrophoresis profile of the Butte 86 proteinpreparations used for the antibody assays: (1) gluten extract (5 μg)and (2) nongluten protein extract (5 μg). Molecular weight markers,shown to the left of the panel, are in kDa. (B,C) Comparison of meanlevels of IgA and IgG antibodies to gluten (B) and nongluten (C) proteinsin patients with celiac disease or dermatitis herpetiformis in comparisonwith unaffected controls, as determined by ELISA. Error bars representthe standard error of the mean.
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fig2: Antibody reactivity to gluten and to nongluten proteins of wheat.(A) Gel electrophoresis profile of the Butte 86 proteinpreparations used for the antibody assays: (1) gluten extract (5 μg)and (2) nongluten protein extract (5 μg). Molecular weight markers,shown to the left of the panel, are in kDa. (B,C) Comparison of meanlevels of IgA and IgG antibodies to gluten (B) and nongluten (C) proteinsin patients with celiac disease or dermatitis herpetiformis in comparisonwith unaffected controls, as determined by ELISA. Error bars representthe standard error of the mean.

Mentions: The gel electrophoresis profiles of the gluten and nonglutenprotein extracts used for the ELISA analyses are shown in Figure 2A. Levels of IgA and IgG class antibodies to theextracted gluten and nongluten protein fractions were measured inall patients and controls. Compared with healthy controls, the twopatient groups displayed significantly higher mean levels of IgA (p < 0.0001 for celiac disease; p <0.001 for dermatitis herpetiformis) and IgG (p <0.0001 for both) antibody to gluten proteins (Figure 2B). In addition, compared with healthy controls, the celiacdisease and dermatitis herpetiformis patient cohorts exhibited significantlyincreased serum IgA (p < 0.0001 for both) andIgG (p < 0.0001 for both) antibody reactivityto the proteins of the nongluten extract (Figure 2C).


Specific nongluten proteins of wheat are novel target antigens in celiac disease humoral response.

Huebener S, Tanaka CK, Uhde M, Zone JJ, Vensel WH, Kasarda DD, Beams L, Briani C, Green PH, Altenbach SB, Alaedini A - J. Proteome Res. (2014)

Antibody reactivity to gluten and to nongluten proteins of wheat.(A) Gel electrophoresis profile of the Butte 86 proteinpreparations used for the antibody assays: (1) gluten extract (5 μg)and (2) nongluten protein extract (5 μg). Molecular weight markers,shown to the left of the panel, are in kDa. (B,C) Comparison of meanlevels of IgA and IgG antibodies to gluten (B) and nongluten (C) proteinsin patients with celiac disease or dermatitis herpetiformis in comparisonwith unaffected controls, as determined by ELISA. Error bars representthe standard error of the mean.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4285749&req=5

fig2: Antibody reactivity to gluten and to nongluten proteins of wheat.(A) Gel electrophoresis profile of the Butte 86 proteinpreparations used for the antibody assays: (1) gluten extract (5 μg)and (2) nongluten protein extract (5 μg). Molecular weight markers,shown to the left of the panel, are in kDa. (B,C) Comparison of meanlevels of IgA and IgG antibodies to gluten (B) and nongluten (C) proteinsin patients with celiac disease or dermatitis herpetiformis in comparisonwith unaffected controls, as determined by ELISA. Error bars representthe standard error of the mean.
Mentions: The gel electrophoresis profiles of the gluten and nonglutenprotein extracts used for the ELISA analyses are shown in Figure 2A. Levels of IgA and IgG class antibodies to theextracted gluten and nongluten protein fractions were measured inall patients and controls. Compared with healthy controls, the twopatient groups displayed significantly higher mean levels of IgA (p < 0.0001 for celiac disease; p <0.001 for dermatitis herpetiformis) and IgG (p <0.0001 for both) antibody to gluten proteins (Figure 2B). In addition, compared with healthy controls, the celiacdisease and dermatitis herpetiformis patient cohorts exhibited significantlyincreased serum IgA (p < 0.0001 for both) andIgG (p < 0.0001 for both) antibody reactivityto the proteins of the nongluten extract (Figure 2C).

Bottom Line: Immunoreactive molecules were identified by tandem mass spectrometry.The main immunoreactive nongluten antibody target proteins were identified as serpins, purinins, α-amylase/protease inhibitors, globulins, and farinins.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Columbia University , New York, New York 10032, United States.

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.

Show MeSH
Related in: MedlinePlus