Autoantibody biomarker discovery in primary open angle glaucoma using serological proteome analysis (SERPA)

Abstract

Glaucoma is an optic neurological disorder and the leading cause of irreversible blindness worldwide worldwide, with primary open angle glaucoma (POAG) as its most prevalent form. An early diagnosis of of the disease is crucial to prevent loss of vision. Mechanisms behind glaucoma pathogenesis are not completely understood, but disease related alterations in the serological autoantibody profile indicate indicate an immunologic component. These changes in immunoreactivity may serve as potential biomarkers biomarkers for glaucoma diagnostics. We aimed to identify novel disease related autoantibodies targeting targeting antigens in the trabecular meshwork as biomarkers to support early detection of POAG. We used used serological proteome analysis (SERPA) for initial autoantibody profiling in a discovery sample set set. The identified autoantibodies were validated by protein microarray analysis in a larger cohort with with 60 POAG patients and 45 control subjects. In this study, we discovered CALD1, PGAM1 and VDAC2 as as new biomarker candidates. With the use of artificial neural networks, the panel of these candidates candidates and the already known markers HSPD1 and VIM was able to classify subjects into POAG patients patients and healthy controls with a sensitivity of 81% and a specificity of 93%. These results suggest suggest the benefit of these potential autoantibody biomarkers in utilization in glaucoma diagnostics diagnostics.