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An Interval on Rat Chromosome 4 Influences IgE Levels in Naive Rats and in Rats Developing Pristane-Induced Arthritis
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology.
Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-91731OAI: oai:DiVA.org:uu-91731DiVA: diva2:164559
Available from: 2004-04-28 Created: 2004-04-28 Last updated: 2010-01-13Bibliographically approved
In thesis
1. More or Less IgE: Therapeutic Vaccines, Adjuvants and Genes and Their Effect on IgE Levels
Open this publication in new window or tab >>More or Less IgE: Therapeutic Vaccines, Adjuvants and Genes and Their Effect on IgE Levels
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Immunoglobulin E (IgE) is an important mediator in atopic allergies. This thesis describes the development of a therapeutic vaccine against IgE and its effects in rats and dogs. The development of an assay to determine IgE levels in dogs, and the finding of a chromosome region in rats that affects IgE levels are also reported.

The vaccine is a chimeric molecule consisting of the constant domains Cε2, Cε3 and Cε4 from IgE. The target domain of the vaccine is the Cε3 domain in the recipient species, which is the domain directly involved in receptor binding, while the flanking regions, Cε2 and Cε4, are from a distantly related mammal. In rats, the vaccine induced an immune response against circulating IgE, which decreased IgE levels by 90% and substantially reduced their allergic symptoms. Further, the effects of adjuvants in rats and dogs were evaluated, and when co-administered with the vaccine certain adjuvants were shown to increase the immune response against IgE. Mineral-oils were the most potent adjuvants in inducing a response against IgE, but metabolizable oils spiked with immunostimulatory substances were also efficient.

It was also shown that the therapeutic vaccine could induce a decrease in IgE levels in adult dogs, even though their initial levels were exceptionally high compared with humans. The IgE levels in 76 dogs ranged between 1 and 41 μg/ml while humans normally have around 150 ng/ml. However, the high IgE levels did not correlate to any specific breed, nor did they distinguish between dogs that were diagnosed as healthy and those suffering from atopic eczema, autoimmunity or skin parasites.

Regulation of total IgE levels probably involves many genes. In the final phase of the study, one candidate locus known to be involved in arthritis susceptibility in rats was investigated, and was found also to affect IgE levels.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 61 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 975
Cell and molecular biology, IgE, Immunoglobulin, Atopic allergy, Vaccine, Adjuvant, Dog, Cell- och molekylärbiologi
National Category
Biochemistry and Molecular Biology
urn:nbn:se:uu:diva-4254 (URN)91-554-5959-5 (ISBN)
Public defence
2004-05-19, C8:305, BMC, Husargatan 3, Uppsala, 09:15
Available from: 2004-04-28 Created: 2004-04-28Bibliographically approved

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