1. Circulating Autoantibody Profiling Identifies LIMS1 as a Potential Target for Pathogenic Autoimmunity in pathologic Myopia.
- Author
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Qi J, Li H, Du Y, Liu Y, He W, Meng J, Wei L, Zhang K, Lu Y, and Zhu X
- Subjects
- Humans, Male, Female, Immunoglobulin G immunology, Immunoglobulin G blood, Middle Aged, Myopia, Degenerative immunology, Myopia immunology, Adult, Autoantibodies immunology, Autoantibodies blood, Retinal Pigment Epithelium pathology, Retinal Pigment Epithelium metabolism, Autoimmunity
- Abstract
High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using a HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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