Title: Interphotoreceptor retinoid binding protein as biomarker in systemic autoimmunity with eye inflictions
Authors: Descamps, Francis J ×
Kangave, Dustan
Cauwe, Bénédicte
Martens, Erik
Geboes, Karel
El-Asrar, Ahmed Abu
Opdenakker, Ghislain #
Issue Date: Dec-2008
Publisher: Wiley-Blackwell Publishing Ltd.
Series Title: Journal of Cellular and Molecular Medicine vol:12 issue:6A pages:2449-2456
Abstract: Autoimmune diseases of the eye, exemplified by Behçet disease and Vogt-Koyanagi-Harada disease, are a major cause of blindness. We studied interphotoreceptor retinoid binding protein (IRBP), a dominant autoimmune antigen in the eye. Aqueous humor samples from 28 patients with active uveitis were analysed for immunoglobulin G (IgG) content as a marker for blood-ocular barrier breakdown and by gelatinase B zymography for the detection of inflammation. The data were correlated with the presence of intact IRBP ( asymptotically equal to 140 kD) as determined by Western blot analysis and with the clinical disease activity. Aqueous humor samples from control eyes and eyes with low disease activity showed positive immunoreactivity for intact IRBP. The IRBP signal weakened or disappeared with higher disease activity. Significant positive correlations were observed between disease activity and levels of matrix metalloproteinase-9 (r(s)= 0.713; p<0.001) and IgG (r(s)= 0.580; p = 0.001). Significant negative correlations were found between levels of IRBP and disease activity (r(s)= -0.520; p = 0.005) and levels of MMP-9 (r(s)= -0.727; p<0.001) and of IgG (r(s)= 0.834; p<0.001). Whereas neutrophil elastase converted intact IRBP into an immunoreactive 55 kD peptide in vitro, the conversion by neutrophil degranulates resembled more the in vivo context with a complete degradation of IRBP. Reversal of inflammation with immunosuppressive therapy was accompanied with reappearance of intact IRBP and disappearance of IgG and MMP-9. The analysis of IRBP proteolysis is useful as a biomarker for uveitis and suggests that inhibition of proteinases might become a therapeutic strategy in an inflammatory context of a damaged blood-ocular barrier.
ISSN: 1582-4934
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Immunobiology (Rega Institute)
Translational Cell & Tissue Research
Laboratory of Genetics of Autoimmunity
× corresponding author
# (joint) last author

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