title: Anti-retinal antibodies in patients with macular telangiectasia type 2.
abstract: OBJECTIVE
  Macular telangiectasia type 2 (MacTel-2) is a retinal disease that can cause loss of central vision. To gain better understanding of the etiology and pathogenesis of MacTel-2, we investigated antigens that prompt the generation of retinal autoantibodies in the serum of patients with MacTel-2.
  
  
  METHODS
  We screened for the presence of retinal autoantibodies in 45 serum samples collected from patients with MacTel-2 and 58 serum samples from healthy control subjects by Western blot. We then isolated and identified three retinal proteins that are putative targets of three of the most frequently detected autoantibodies in the serum of patients with MacTel-2 using chromatographic fractionation and liquid chromatography coupled to tandem mass spectrometry. We also validated the retinal location of the three antigens by immunohistochemisty using MacTel-2 sera as primary antibodies and commercial antibodies.
  
  
  RESULTS
  Retinal autoantibodies were detected in a significantly higher proportion of patients with MacTel-2 than in controls (31 of 45 [69%] vs. 9 of 58 [16%], P < 0.0001). The three antigens that were targeted by the most frequently detected MacTel-2 autoantibodies were identified as glycogen debranching enzyme (hereafter AGL, named for the gene symbol AGL), retinol-binding protein 3 (RBP3), and creatine kinase type B (CK-B); autoantibodies against these antigens were found in four, eleven, and nine MacTel-2 serum samples, respectively.
  
  
  CONCLUSIONS
  We found that most patients with MacTel-2 possess retinal autoantibodies, the most prevalent of which were directed against AGL, RBP3, and CK-B. The localization of retinal proteins bound by AGL, RBP3, and CK-B autoantibodies is consistent with their putative physiological functions. These findings provide potentially novel mechanisms for the etiology and pathogenesis of MacTel-2.
authors.affiliation: Save Sight Institute, The University of Sydney, Sydney, Australia. ling.zhu@sydney.edu.au
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
authors.forename: Weiyong
authors.initials: W
authors.lastname: Shen
authors.forename: Meidong
authors.initials: M
authors.lastname: Zhu
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Coorey
authors.forename: An P
authors.initials: AP
authors.lastname: Nguyen
authors.forename: Daniel
authors.initials: D
authors.lastname: Barthelmes
authors.forename: Mark C
authors.initials: MC
authors.lastname: Gillies
mesh_terms: D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D052276:Creatine Kinase, BB Form / Q000276:immunology*; D005136:Eye Proteins / Q000276:immunology*; D005260:Female; D006004:Glycogen Debranching Enzyme System / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012160:Retina / Q000276:immunology* / Q000473:pathology; D058456:Retinal Telangiectasis / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000276:immunology*; D016036:Seroepidemiologic Studies; D055815:Young Adult; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D001323:Autoantibodies; D052276:Creatine Kinase, BB Form; D005136:Eye Proteins; D006004:Glycogen Debranching Enzyme System; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial
keywords: autoantibody; creatine kinase type B; glycogen debranching enzyme; macular telangiectasia type 2; retinol-binding protein 3