Author: Christina Korb
Co-authors: Katrin Lorenz, Vanessa Beutgen, Dominik Wolters, Norbert Pfeiffer, Franz H. Grus
Abstract
Purpose: Anti-retinal autoantibodies might play an important role in the pathogenesis of AMD. We identified antibodies against retinal antigens in patients with neovascular AMD treated with ranibizumab and healthy subjects.Setting/Venue: Department of Ophthalmology, University Medical Center, Johannes Gutenberg-University Mainz, Germany.
Methods: This study was designed as a prospective parallel-group interventional phase IV single center trial. Serological levels of IgG immunreactivities were analysed by protein microarrays in patients suffering from neovascular AMD treated with intravitreal ranibizumab. Fifty patients ≥ 50 years of age with neovascular AMD and a visual acuity of 20/400 or better in the study eye were included and followed over six months. Initially, three intravitreal ranibizumab injections were given, followed by an individual intravitreal therapy interval based on the clinical progress (pro re nata). Blood samples were taken every 4 weeks to assess time and treatment dependent changes. As a control group, 20 healthy volunteers were recruited. To assess the group differences of the tested autoantibodies between the groups at different time points a non-parametric test was applied.
Results: Anti-transthyretin levels were significantly decreased after six months in the AMD group compared to the control group (p=0.004). Anti carbonic anhydrase 2 (p=0.042), aconitate hydratase (p=0.043), 60 kDa heat shock protein (p=0.034), myelin basic protein (p=0.001), super oxid dismutase (p=0.015), gamma-synuclein (p=0.043) and serum albumin (p=0.048) antibodies were significantly increased, when comparing these two groups. Also, a significant increase in autoantibody levels from baseline to six months in the AMD group was observed for mucin (p=0.019), brain-derived neurotrophic factor (p=0.005), calreticulin (p=0.026) and neurotrophin-3 (p=0.011). For some autoantibodies, a significant increase between the control group and the AMD group at six months, as well as between AMD at baseline and at month six was observed. These antibodies target the proteins serotransferrin, opioid growth factor receptor, 60kDa chaperonin 2, neurotrophin-4, dermcidin, clusterin and vascular endothelial growth factor.
Conclusions: Significant increased and decreased levels of some autoantibodies could be demonstrated between the control group and the AMD group at month six Several autoantibodies show significant increased serological levels between the AMD patients and the control group, as well as between baseline and after six months of intravitreal ranibizumab treatment.
Financial Disclosure: A grant was provided by Novartis Pharma GmbH.