Dubucquoi, S., Proust-Lemoine, E., Kemp, E.H. et al. (8 more authors) (2015) Serological proteome analysis reveals new specific biases in the IgM and IgG autoantibody repertoires in autoimmune polyendocrine syndrome type 1. Autoimmunity. ISSN 0891-6934
Abstract
Objective: Autoimmune polyendocrine syndrome type 1 (APS 1) is caused by mutations in the AIRE gene that induce intrathymic T-cell tolerance breakdown, which results in tissue-specific autoimmune diseases.
Design: To evaluate the effect of a well-defined T-cell repertoire impairment on humoral self-reactive fingerprints, comparative serum self-IgG and self-IgM reactivities were analyzed using both one- and two-dimensional western blotting approaches against a broad spectrum of peripheral tissue antigens. Methods: Autoantibody patterns of APS 1 patients were compared with those of subjects affected by other autoimmune endocrinopathies (OAE) and healthy controls.
Results: Using a Chi-square test, significant changes in the Ab repertoire were found when intergroup patterns were compared. A singular distortion of both serum self-IgG and self-IgM repertoires was noted in APS 1 patients. The molecular characterization of these antigenic targets was conducted using a proteomic approach. In this context, autoantibodies recognized more significantly either tissue-specific antigens, such as pancreatic amylase, pancreatic triacylglycerol lipase and pancreatic regenerating protein 1α, or widely distributed antigens, such as peroxiredoxin-2, heat shock cognate 71-kDa protein and aldose reductase. As expected, a well-defined self-reactive T-cell repertoire impairment, as described in APS 1 patients, affected the tissue-specific self-IgG repertoire. Interestingly, discriminant IgM reactivities targeting both tissue-specific and more widely expressed antigens were also specifically observed in APS 1 patients. Using recombinant targets, we observed that post translational modifications of these specific antigens impacted upon their recognition.
Conclusions: The data suggest that T-cell-dependent but also T-cell-independent mechanisms are involved in the dynamic evolution of autoimmunity in APS 1.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 Taylor & Francis. This is an author produced version of a paper subsequently published in Autoimmunity. Uploaded in accordance with the publisher's self-archiving policy. This is an Accepted Manuscript of an article published by Taylor & Francis in Autoimmunity on 27.8.2015, available online: http://wwww.tandfonline.com/10.3109/08916934.2015.1077230. This is an Accepted Manuscript of an article published by Taylor & Francis in [JOURNAL TITLE] on [date of publication], available online: http://wwww.tandfonline.com/[Article DOI].” |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Human Metabolism (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 03 Dec 2015 16:21 |
Last Modified: | 31 Oct 2016 02:41 |
Published Version: | http://dx.doi.org/10.3109/08916934.2015.1077230 |
Status: | Published |
Publisher: | Taylor & Francis |
Refereed: | Yes |
Identification Number: | 10.3109/08916934.2015.1077230 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:90264 |