{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:38:28Z","timestamp":1794008308413,"version":"4.8.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Increasing evidence suggests that autoimmune responses are involved in the pathogenesis of age-related macular degeneration (AMD). This study aimed to characterize changes in serum autoantibody-captured retinal antigens in patients with different AMD subtypes, in order to gain further insight into the immunological mechanisms associated with AMD progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum samples were collected from healthy controls (CTRL, n = 15) and patients with early AMD (n = 15), intermediate AMD (Int. AMD, n = 15), late AMD (n = 15), neovascular AMD with type 1 macular neovascularization (nAMD type 1, n = 10), and neovascular AMD with type 2 macular neovascularization (nAMD type 2, n = 10). Serum antibodies were isolated using Protein G magnetic beads and incubated with porcine retinal lysates to capture antigen\u2013antibody complexes. After elution, the captured retinal antigens were subjected to proteomic analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mass spectrometry identified 91 differentially captured retinal antigen targets across AMD subtypes. Compared with controls, 11, 9, 11, 18, and 22 retinal antigen targets were significantly increased in serum samples from patients with early AMD, intermediate AMD, late AMD, nAMD type 1, and nAMD type 2, respectively. Conversely, 14, 11, 9, 10, and 20 retinal antigen targets were decreased in the corresponding AMD subtypes, respectively (FDR &amp;lt; 0.05; p &amp;lt; 0.05). Selected mass spectrometryderived retinal antigen targets were further evaluated in serum and tear samples using antigen microarray analysis. Consistent with the proteomics results, anti-ATP5A1, anti-HIST2H2AA3, and anti-PFKM autoantibody levels were significantly increased in tears from patients with nAMD type 2 (p = 0.03, p = 0.01, and p = 0.04, respectively). In addition, anti-FTH1 autoantibody levels were decreased in serum from patients with nAMD type 1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Comprehensive screening of serum autoantibody-captured retinal antigens across AMD stages, together with pathway enrichment and STRING network analyses, revealed subtype-specific immune alterations. These findings provide new insights into the immunopathological features of AMD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1824524","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:59:14Z","timestamp":1783490354000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Stage-associated immunoproteomic profiling of serum autoantibody-captured retinal antigens in age-related macular degeneration"],"prefix":"10.3389","volume":"17","author":[{"given":"Hao","family":"Lin","sequence":"first","affiliation":[{"name":"Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz","place":["Mainz, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Wolfrum","sequence":"additional","affiliation":[{"name":"Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz","place":["Mainz, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia F.","family":"Kempf","sequence":"additional","affiliation":[{"name":"Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz","place":["Mainz, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Wolters","sequence":"additional","affiliation":[{"name":"Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz","place":["Mainz, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natarajan","family":"Perumal","sequence":"additional","affiliation":[{"name":"Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical 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