title: Anti-retinal pigment epithelium antibodies in acute exudative polymorphous vitelliform maculopathy: a new hypothesis about disease pathogenesis.
abstract: OBJECTIVE
  To investigate the etiology of acute exudative polymorphous vitelliform maculopathy (AEPVM) in a patient with metastatic melanoma, undiagnosed at initial examination, by testing for autoimmune mechanisms.
  
  
  METHODS
  Serum samples were obtained from a 50-year-old man with AEPVM and metastatic unknown primary melanoma during the acute stage and 3 years later when subretinal fluid had resolved and melanoma was in remission (AEPVM convalescent stage). Western immunoblots using both serum samples against human donor retinal extract and cultured primary human retinal pigment epithelium (RPE) cell extract were performed to identify antiretinal and anti-RPE antibodies. Serum samples from 5 unaffected participants were tested as controls. Protein identification was performed using 2-dimensional gel electrophoresis and mass spectrometry and was then confirmed by blotting against purified protein.
  
  
  RESULTS
  Western immunoblots of the patient's serum against human donor retinal extract and RPE cell extract demonstrated several antiretinal antibodies, as well as anti-RPE antibodies against a 26-kDa protein that was identified as peroxiredoxin 3 (PRDX3). Serum reactivity against PRDX3 was greatly decreased in the convalescent-stage serum sample compared with the acute-stage serum sample, while results of retinal extract Western immunoblots remained essentially unchanged. Five separate serum samples from participants without AEPVM had no autoantibodies against PRDX3.
  
  
  CONCLUSIONS
  Paraneoplastic autoimmune reaction against RPE, with PRDX3 as the putative antigen, may be a cause of AEPVM. This is the first report to date linking a human RPE disease with anti-RPE antibodies against a heretofore undetermined putative protein. Testing for RPE autoantibodies may be useful in exploring the pathogenesis of other presumed RPE-related diseases.
authors.affiliation: W K Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Koreen
authors.forename: Shirley X
authors.initials: SX
authors.lastname: He
authors.forename: Mark W
authors.initials: MW
authors.lastname: Johnson
authors.forename: Richard E
authors.initials: RE
authors.lastname: Hackel
authors.forename: Naheed W
authors.initials: NW
authors.lastname: Khan
authors.forename: John R
authors.initials: JR
authors.lastname: Heckenlively
mesh_terms: D000208:Acute Disease; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D015153:Blotting, Western; D002478:Cells, Cultured; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D015180:Electrophoresis, Gel, Two-Dimensional; D004596:Electroretinography; D005122:Exudates and Transudates; D005451:Fluorescein Angiography; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D013058:Mass Spectrometry; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology / Q000556:secondary; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy / Q000473:pathology; D010257:Paraneoplastic Syndromes / Q000175:diagnosis / Q000276:immunology*; D061105:Peroxiredoxin III; D054464:Peroxiredoxins / Q000097:blood*; D055213:Retinal Pigment Epithelium / Q000276:immunology*; D000077204:Temozolomide; D041623:Tomography, Optical Coherence; D057826:Vitelliform Macular Dystrophy / Q000175:diagnosis / Q000276:immunology*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D001323:Autoantibodies; D001324:Autoantigens; D003606:Dacarbazine; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D000077204:Temozolomide