Kininogen in autoimmune uveitis: decrease in peripheral blood stream versus increase in target tissue.
OBJECTIVE
Equine recurrent uveitis (ERU) is an incurable disease affecting the inner eye that leads to blindness, through activated T cells that pass the blood-retinal barrier and destroy the retina. Serum markers are a desirable choice for monitoring development of disease, as serum is easy accessible and the markers could serve to predict the beginning of disease or an imminent relapse.


METHODS
In this study, serum proteomes (depleted of high-abundance serum proteins) of horses with ERU and healthy controls were compared with the 2-D DIGE (two-dimensional gel electrophoresis) technique to identify differentially expressed proteins. The expression pattern of a candidate protein in retina and vitreous was validated by Western blots and immunohistochemistry.


RESULTS
Ten differentially expressed proteins could be identified by mass spectrometry (MALDI-TOF/TOF). Five proteins--IgM, IgG4 hc, serotransferrin, alpha-2HS-glycoprotein, and complement factor B--were upregulated in the uveitic state, whereas the five proteins albumin, apolipoprotein A-IV and H, IgG5 hc, and high-molecular-weight kininogen (HK) showed a significantly lower expression in sera of uveitis cases. Of interest, kininogen was significantly upregulated in the target tissues vitreous and retina. HK is a plasma protein with multiple physiological functions, with an important role in inflammation and promoting neovascularization. Most interesting is the as of yet unaddressed association of HK with uveitis. Immunohistochemistry showed coexpression of kininogen and VEGF in inflamed eyes.


CONCLUSIONS
Since neovascularization plays a major role in the pathogenesis of uveitis, the identification of a proangiogenic factor in the retina presents an important finding and may contribute to elucidating the pathogenesis of uveitis.
Zipplies
Johanna K
JK
Institute of Animal Physiology, Department of Veterinary Sciences, Ludwig-Maximilians University, Munich, Germany.
Hauck
Stefanie M
SM
Schoeffmann
Stephanie
S
Amann
Barbara
B
van der Meijden
Christiaan H
CH
Stangassinger
Manfred
M
Ueffing
Marius
M
Deeg
Cornelia A
CA
D000818:Animals; D001324:Autoantigens / Q000097:blood; D001327:Autoimmune Diseases / Q000097:blood / Q000378:metabolism / Q000662:veterinary*; D001798:Blood Proteins / Q000378:metabolism; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D019084:Fluorescent Antibody Technique, Indirect; D006734:Horse Diseases / Q000097:blood* / Q000378:metabolism; D006736:Horses; D019679:Kininogen, High-Molecular-Weight / Q000097:blood*; D007704:Kininogens / Q000378:metabolism; D012008:Recurrence; D012160:Retina / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015854:Up-Regulation; D014605:Uveitis / Q000097:blood / Q000378:metabolism / Q000662:veterinary*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism
D001324:Autoantigens; D001798:Blood Proteins; D019679:Kininogen, High-Molecular-Weight; D007704:Kininogens; D042461:Vascular Endothelial Growth Factor A