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

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Kei Morohoshi Chuan-Hui Kuo Masaharu Ohbayashi Nishal Patel Victor N. Chong Alan C. Bird Santa J. Ono

Abstract

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.

Article Details

How to Cite
MOROHOSHI, Kei et al. Anti-glutamine synthetase and other potential autoantibody biomarkers in the sera of patients with age-related macular degeneration. Medical Research Archives, [S.l.], n. 3, july 2015. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/121>. Date accessed: 28 mar. 2024.
Keywords
age-related macular degeneration; anti-retinal antibody; autoantibody; autoimmunity; biomarker; glutamine synthetase; proteomics
Section
Research Articles