Interphotoreceptor retinoid-binding protein as biomarker in systemic autoimmunity with eye inflictions

Autoimmune diseases of the eye, exemplified by Beh cet 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 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 (≈140 kD) as determined by Western blot analysis and with the clinical disease activity. 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) (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.