Autoantibody signature for age-related macular degeneration

Recent findings indicate that immunologic factors, in particular autoantibodies, are involved in the pathogenesis of age-related macular degeneration (AMD). To reveal an autoantibody profile for AMD and identify biomarkers for progression of this disease, we performed an antigen microarray printed with 66 kinds of AMD-associated molecules using serum samples from patients with dry and wet AMD and from age-matched healthy controls. Sera from the AMD groups contained significantly higher levels of IgG and IgM antibodies to 32 ocular antigens and immune molecules, respectively, than sera from the control group and demonstrated the highest IgG reactivity to Helicobacter pylori antigen and highest IgM reactivity to complement C3. Anti–complement C4 IgG (odds ratio, OR = 16.4) and anti-cytomegalovirus IgM (OR = 13.0) were best correlated with the development of dry AMD, and anti–apolipoprotein E IgG (OR = 14.5) and anti–complement factor H IgM (OR = 6.0) were the most reliable biomarkers for progression from dry to wet AMD. Moreover, IgGs purified from sera of patients with AMD contained high reactivity to glutamine synthetase (GS) and inhibited GS activity in a dose-dependent manner. Ocular expression of GS decreased with age in mice, suggesting that the accumulation of glutamate, which has strong neurotoxicity, contributes to retinal degeneration. Our data demonstrate that patient seroreactivities to specific ocular antigens might be used as biomarkers for AMD and that anti-GS IgG could be associated with the pathogenesis of AMD. Medical Research Archives July 2015 Issue 3 Copyright © 2015, Knowledge Enterprises Incorporated. All rights reserved. 2 Keywords— age-related macular degeneration; anti-retinal antibody; autoantibody; autoimmunity; biomarker; glutamine synthetase; proteomics Medical Research Archives July 2015 Issue 3 Copyright © 2015, Knowledge Enterprises Incorporated. All rights reserved. 3