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Measuring autoantibodies against IL17F and IL-22 in  autoimmune polyendocrine syndromme type I by radioligand binding assay using fusion proteins
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2011 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 74, no 3, 327-333 p.Article in journal (Refereed) Published
Abstract [en]

Autoantibodies against interleukin (IL)-17A, IL-17F and IL-22 have recently been described in patients with autoimmune polyendocrine syndrome type I (APS I), and their presence is reported to be highly correlated with chronic mucocutaneous candidiasis (CMC). The aim of this study was to develop a robust high-throughput radioligand binding assays (RLBA) measuring IL-17F and IL-22 antibodies, to compare them with current enzyme-linked immunosorbent assays (ELISA) of IL-17F and IL-22 and, moreover, to correlate the presence of these antibodies with the presence of CMC. Interleukins are small molecules, which makes them difficult to express in vitro. To overcome this problem, they were fused as dimers, which proved to increase the efficiency of expression. A total of five RLBAs were developed based on IL-17F and IL-22 monomers and homo- or heterodimers. Analysing the presence of these autoantibodies in 25 Norwegian APS I patients revealed that the different RLBAs detected anti-IL-17F and anti-IL-22 with high specificity, using both homo- and heterodimers. The RLBAs based on dimer proteins are highly reproducible with low inter- and intravariation and have the advantages of high throughput and easy standardization compared to ELISA, thus proving excellent choices for the screening of IL-17F and IL-22 autoantibodies.

Place, publisher, year, edition, pages
2011. Vol. 74, no 3, 327-333 p.
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-153870DOI: 10.1111/j.1365-3083.2011.02573.xISI: 000293635900014PubMedID: 21535082OAI: oai:DiVA.org:uu-153870DiVA: diva2:418184
Available from: 2011-05-20 Created: 2011-05-20 Last updated: 2015-08-12Bibliographically approved
In thesis
1. Immunological Studies using Human and Canine Model Disorders
Open this publication in new window or tab >>Immunological Studies using Human and Canine Model Disorders
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Immunologiska studier av modellsjukdomar i människa och hund
Abstract [en]

The studies presented in this thesis focus on human and canine models for autoimmune disease, with the main aim to gain new knowledge about disease mechanisms and to further evaluate the dog as a model for autoimmune disease.

Autoimmune Polyendocrine Syndrome type 1 (APS-1) is a hereditary human multiorgan disease caused by mutations in the autoimmune regulator (AIRE) gene. Hallmarks of APS-1 are chronic mucocutaneous candidiasis caused by Candida albicans, together with the autoimmune endocrine disorders hypoparathyroidism and adrenocortical failure. Many human diseases have an equivalent disease in dogs. Because humans share environment, and in part life style with the dogs they provide an interesting model for further genetic studies.

Immune responses to Candida albicans in APS-1 patients displayed an increased secretion of the proinflammatory cytokine IL-17A and similar results were also found in AIRE deficient mice. Anticytokine autoantibodies to IL-17A, IL-17F and IL-22 were detected in APS-1 patients, and a radioligand binding assay for measuring these autoantibodies was developed and evaluated.

In the canine studies we investigated whether canine diabetes mellitus could serve as a model for human autoimmune diabetes mellitus. Furthermore, we investigated type I IFN responses in Nova Scotia duck tolling retriever dogs with a systemic autoimmune disease resembling human SLE.

Four assays were used in search for signs of humoral autoimmunity in diabetic dogs. However, no evidence for a type 1 diabetes-like phenotype in dogs was found. Sera from Nova Scotia duck tolling retrievers suffering from steroid-responsive meningitis arteritis elicited an increased expression of IFN-inducible genes in the canine MDCK cell line. This suggests that these dogs have an IFN signature, as seen in human SLE.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 49 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 721
Keyword
Autoimmunity, T cell, T helper cell, B cell, Autoantibodies, Interferon, Interleukin, Dogs, APS-1, Candida albicans, fungus
National Category
Basic Medicine
Research subject
Immunology; Medicine
Identifiers
urn:nbn:se:uu:diva-160550 (URN)978-91-554-8211-4 (ISBN)
Public defence
2011-12-08, Enghoffsalen, Akademiska sjukhuset. Ingång 50, bv, Uppsala, 09:15 (Swedish)
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Supervisors
Available from: 2011-11-16 Created: 2011-10-25 Last updated: 2011-11-23Bibliographically approved

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