| Activation-induced cytidine deaminase (AID)-associated multigene signature to assess impact of AID in etiology of diseases with inflammatory component. | |
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MedLine Citation:
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PMID: 21984922 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation-induced cytidine deaminase (AID) is expressed in B cells within germinal centers and is critically involved in class switch recombination and somatic hypermutation of immunoglobulin loci. Functionally active AID can additionally be detected within ectopic follicular structures developed at sites of chronic inflammation. Furthermore, AID may target non-Ig genes in B- and non-B-cell background. Therefore, AID-associated effects are of increasing interest in disease areas such as allergy, inflammation, autoimmunity, and cancer.Pathway- or disease-relevant multigene signatures have attracted substantial attention for therapeutic target proposal, diagnostic tools, and monitoring of therapy response. To delineate the impact of AID in etiology of multifactorial diseases, we designed the AID-associated 25-gene signature. Chronic rhinosinusitis with nasal polyps was used as an inflammation-driven airway disease model; high levels of IgE have been previously shown to be present within polyp tissue. Expression levels of 16 genes were found to be modulated in polyps including AID, IgG and IgE mature transcripts which reflect AID activity; clustering algorithm revealed an AID-specific gene signature for the disease state with nasal polyp. Complementary, AID-positive ectopic lymphoid structures were detected within polyp tissues by in situ immunostaining. Our data demonstrate the class switch recombination and somatic hypermutation events likely taking place locally in the airways and in addition to the previously highlighted markers and/or targets as IL5 and IgE suggest novel candidate genes to be considered for treatment of nasal polyposis including among others IL13 and CD23. Thus, the algorithm presented herein including the multigene signature approach, analysis of co-regularities and creation of AID-associated functional network gives an integrated view of biological processes and might be further applied to assess role of altered AID expression in etiology of other diseases, in particular, aberrant immunity and cancer. |
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Authors:
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Diana Mechtcheriakova; Yury Sobanov; Gabriele Holtappels; Erika Bajna; Martin Svoboda; Markus Jaritz; Claus Bachert; Erika Jensen-Jarolim |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-10-03 |
Journal Detail:
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Title: PloS one Volume: 6 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2011 |
Date Detail:
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Created Date: 2011-10-10 Completed Date: 2012-01-30 Revised Date: 2012-05-21 |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e25611 Citation Subset: IM |
Affiliation:
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Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. diana.mechtcheriakova@meduniwien.ac.at |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alternative Splicing
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genetics Chronic Disease Cluster Analysis Cytidine Deaminase / genetics*, metabolism Databases, Genetic Gene Expression Profiling* Gene Expression Regulation Gene Regulatory Networks / genetics Humans Inflammation / complications, enzymology*, etiology* Nasal Polyps / complications, enzymology, genetics, pathology RNA, Messenger / genetics, metabolism Sinusitis / enzymology, etiology*, genetics*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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P 22441-B13//Austrian Science Fund FWF |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase |
| Comments/Corrections | |
Erratum In:
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PLoS One. 2012;7(5): doi/10.1371/annotation/2eba0189-04c1-4dce-a85a-c7f2c7089938 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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