title: Presence of retinal pericyte-reactive autoantibodies in diabetic retinopathy patients.
abstract: The loss of retinal pericytes (RPCs) is a hallmark of early stage diabetic retinopathy (DR), but the mechanism underlying RPC death is unclear. Although it was postulated in previous studies using bovine RPCs that autoantibodies against RPCs might develop and induce RPC death, it is unknown whether autoantibodies against cell-surface antigens on human RPCs exist in DR patients, whether such autoantibodies contribute to RPC damage/loss, and if they do, through which mechanism. We screened serum samples from DR patients and controls using primary human RPCs and found that that levels of IgGs reactive to RPCs were significantly higher in the DR group than the control group. Serum samples with higher RPC-reactive IgG levels induced more severe complement-mediated RPC damage than those with lower RPC-reactive IgG levels. We also assessed levels of the complement-activation products C3a, C4a and C5a in these serum samples, and found that serum levels of C3a and C5a, but not C4a, were higher in the DR group than control group. These data provide evidence the first time showing that autoantibodies against RPCs can develop in DR patients, and that these autoantibodies could contribute to pericyte damage through complement activation.
authors.affiliation: Tianjin Medical University Eye Hospital, Eye Institute &School of Optometry and Ophthalmology, Tianjin, China.|Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Palmetto Retina Center, West Columbia, South Carolina, USA.
authors.forename: John
authors.initials: J
authors.lastname: Payne
authors.affiliation: Department of Ophthalmology, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Xingjun
authors.initials: X
authors.lastname: Fan
authors.affiliation: Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: John
authors.initials: J
authors.lastname: Fung
authors.affiliation: Tianjin Medical University Eye Hospital, Eye Institute &School of Optometry and Ophthalmology, Tianjin, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Kern
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
mesh_terms: D000368:Aged; D000954:Antigens, Surface / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D002478:Cells, Cultured; D003167:Complement Activation; D015926:Complement C3a / Q000378:metabolism; D015934:Complement C4a / Q000378:metabolism; D015936:Complement C5a / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000097:blood / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020286:Pericytes / Q000276:immunology / Q000473:pathology*; D012160:Retina / Q000166:cytology* / Q000276:immunology / Q000473:pathology
chemical_list: D000954:Antigens, Surface; D001323:Autoantibodies; D007074:Immunoglobulin G; D015926:Complement C3a; D015934:Complement C4a; D015936:Complement C5a
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