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Retinal pigment epithelium and microglia express the CD5 antigen-like protein, a novel autoantigen in age-related macular degeneration.

dc.contributor.author Iannaccone, Alessandro
dc.contributor.author Hollingsworth, TJ
dc.contributor.author Koirala, Diwa
dc.contributor.author New, David D
dc.contributor.author Lenchik, Nataliya I
dc.contributor.author Beranova-Giorgianni, Sarka
dc.contributor.author Gerling, Ivan C
dc.contributor.author Radic, Marko Z
dc.contributor.author Giorgianni, Francesco
dc.date.accessioned 2019-03-01T22:02:24Z
dc.date.available 2019-03-01T22:02:24Z
dc.date.issued 2017-02
dc.identifier S0014-4835(16)30537-1
dc.identifier.issn 0014-4835
dc.identifier.issn 1096-0007
dc.identifier.uri https://hdl.handle.net/10161/18120
dc.description.abstract We report on a novel autoantigen expressed in human macular tissues, identified following an initial Western blot (WB)-based screening of sera from subjects with age-related macular degeneration (AMD) for circulating auto-antibodies (AAbs) recognizing macular antigens. Immunoprecipitation, 2D-gel electrophoresis (2D-GE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), direct enzyme-linked immunosorbent assays (ELISA), WBs, immunohistochemistry (IHC), human primary and ARPE-19 immortalized cell cultures were used to characterize this novel antigen. An approximately 40-kDa autoantigen in AMD was identified as the scavenger receptor CD5 antigen-like protein (CD5L), also known as apoptosis inhibitor of macrophage (AIM). CD5L/AIM was localized to human RPE by IHC and WB methods and to retinal microglial cells by IHC. ELISAs with recombinant CD5L/AIM on a subset of AMD sera showed a nearly 2-fold higher anti-CD5L/AIM reactivity in AMD vs. Control sera (p = 0.000007). Reactivity ≥0.4 was associated with 18-fold higher odds of having AMD (χ2 = 21.42, p = 0.00063). Circulating CD5L/AIM levels were also nearly 2-fold higher in AMD sera compared to controls (p = 0.0052). The discovery of CD5L/AIM expression in the RPE and in retinal microglial cells adds to the known immunomodulatory roles of these cells in the retina. The discovery of AAbs recognizing CD5L/AIM identifies a possible novel disease biomarker and suggest a potential role for CD5L/AIM in the pathogenesis of AMD in situ. The possible mechanisms via which anti-CD5L/AIM AAbs may contribute to AMD pathogenesis are discussed. In particular, since CD5L is known to stimulate autophagy and to participate in oxidized LDL uptake in macrophages, we propose that anti-CD5L/AIM auto-antibodies may play a role in drusen biogenesis and inflammatory RPE damage in AMD.
dc.language eng
dc.publisher Elsevier BV
dc.relation.ispartof Experimental eye research
dc.relation.isversionof 10.1016/j.exer.2016.12.006
dc.subject Microglia
dc.subject Retina
dc.subject Cell Line
dc.subject Macrophages
dc.subject Humans
dc.subject Macular Degeneration
dc.subject Autoantigens
dc.subject Microscopy, Confocal
dc.subject Blotting, Western
dc.subject Enzyme-Linked Immunosorbent Assay
dc.subject Electrophoresis, Gel, Two-Dimensional
dc.subject Immunohistochemistry
dc.subject Autoimmunity
dc.subject Aged
dc.subject Aged, 80 and over
dc.subject Middle Aged
dc.subject Female
dc.subject Male
dc.subject Tandem Mass Spectrometry
dc.subject Retinal Pigment Epithelium
dc.subject CD5 Antigens
dc.title Retinal pigment epithelium and microglia express the CD5 antigen-like protein, a novel autoantigen in age-related macular degeneration.
dc.type Journal article
dc.date.updated 2019-03-01T22:02:23Z
pubs.begin-page 64
pubs.end-page 74
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Ophthalmology, Vitreoretinal Diseases & Surgery
pubs.organisational-group Ophthalmology
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 155
duke.contributor.orcid Iannaccone, Alessandro|0000-0001-5737-8424


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