Autoantigens in the trabecular meshwork and glaucoma-specific alterations in the natural autoantibody repertoire

Clinical & Translational Immunology
Vanessa M BeutgenFranz H Grus

Abstract

Primary open-angle glaucoma (POAG) is a neurodegenerative disorder leading to a gradual vision loss caused by progressive damage to the optic nerve. Immunological processes are proposed to be involved in POAG pathogenesis. Altered serological autoantibody levels have been frequently reported, but complete analyses of the natural autoantibodies with respect to disease-related alterations are scarce. Here, we provide an explorative analysis of pathways and biological processes that may involve naturally immunogenic proteins and highlight POAG-specific alterations. Mass spectrometry-based antibody-mediated identification of autoantigens (MS-AMIDA) was carried out in healthy and glaucomatous trabecular meshwork (TM) cell lines, using antibody pools purified from serum samples of 30 POAG patients and 30 non-glaucomatous subjects. Selected antigens were validated by protein microarray (n = 120). Bioinformatic assessment of identified autoantigens, including Gene Ontology (GO) enrichment analysis and protein-protein interaction networks, was applied. Overall, we identified 106 potential autoantigens [false discovery rate (FDR) < 0.01], from which we considered 66 as physiological targets of natural autoantibodies. Twenty-one autoantig...Continue Reading

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Methods Mentioned

BETA
immunoprecipitation
acetylation
PCA

Software Mentioned

AMIDA
Metascape
DAVID
MCODE
MaxQuant
MS
Statistica
Imagene
Perseus

Related Concepts

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