Anti-glutamine synthetase and other potential autoantibody biomarkers in the sera of patients with age-related macular degeneration

Recent findings indicate that immunological factors, in particular a possible autoimmune response, 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 analysis of serum samples from patients with AMD and healthy controls. Sera from the AMD groups contained higher levels of IgG and IgM antibodies to various ocular antigens and immune molecules, respectively, when compared to the normal group. 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 AMD patients contained high reactivity to glutamine synthetase (GS) and inhibited activity of GS 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 the disease.