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Inflammatory mediators in the aqueous humor from patients with uveitis associated with Behçet’s disease and Vogt‐Koyanagi‐Harada disease
Author(s) -
ABU EL ASRAR A,
DESCAMPS F,
KANGAVE D,
CAUWE B,
MARTENS E,
GEBOES K,
OPDENAKKER G
Publication year - 2010
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2010.4156.x
Subject(s) - zymography , uveitis , medicine , context (archaeology) , gelatinase , autoimmune disease , immunology , inflammation , endocrinology , matrix metalloproteinase , antibody , biology , paleontology
Purpose We studied interphotoreceptor retinoid‐binding protein (IRBP), a dominant autoimmune antigen in the eye. Methods Aqueous humour 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 (approximately 140 kD) as determined by Western blot analysis and with the clinical disease activity. Results Aqueous humour 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 gelatinase B/matrix metalloproteinase‐9 (MMP‐9) (rs=0.713; P<0.001) and IgG (rs=0.580; P=0.001). Significant negative correlations were found between levels of IRBP and disease activity (rs=‐0.520; P=0.005) and levels of MMP‐9 (rs=‐0.727; P<0.001) and of IgG (rs=‐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. Conclusion 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.