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Title: Identification of gp130 - an antigenic target in small vessel vasculitis expressed on glomerular endothelium
Author: Kain, Renate
ISNI:       0000 0004 2682 6636
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2009
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The purpose of my thesis was to capitalise on the development of mammalian expression cloning and the advanced proteomics facilities in Aberdeen to identify gp130.  My thesis had four specific objectives: (i) to undertake biochemical experiments to characterise the glycosylation pattern of gp130 and to improve the efficiency of techniques for purifying it both in its native state and after deglycosylation; (ii) to develop a mammalian expression cloning strategy for identifying gp130; (iii) to purify sufficient gp130 for separation on 2-D gels to permit identification of potential candidate molecules by amino acid sequencing using mass spectrometry and Edmann degradation; and (iv) to characterise proteins that co-immunoprecipitate with gp130 and use existing knowledge about these associated proteins to suggest potential candidate molecules for gp130 itself. None of the approaches proved decisive but by combining knowledge gained from all of them I was ultimately able to hypothesise that gp130 was a unique form of aminopeptidase N/CD13 (APN/CD13) and to prove it by showing 293T17 cells transfected with a cDNA encoding CD13 expressed gp130 on their plasma membranes.  APN/CD13 in an ectoenzyme otherwise expressed on neo-angiogenic endothelial cells, monocytes and lymphocytes. It has essential roles in angiogenesis and vascular control, and in immunity and inflammation.  Future studies will need to determine how Ag11 binding APN/CD13 differs from other forms of CD13 and why this form is selectively expressed by renal microvascular and placental microvascular endothelium.  My thesis opens the way for detailed studies of the role of antibodies to APN/CD13 in pauci-immune FNGN.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available