title: Serum Autoantibody Profiling of Patients with Paraneoplastic and Non-Paraneoplastic Autoimmune Retinopathy.
abstract: OBJECTIVE
  Although multiple serum antiretinal autoantibodies (ARAs) have been reported in patients with paraneoplastic and non-paraneoplastic autoimmune retinopathy ((n)pAIR), not all retinal antigens involved in (n)pAIR are specified. This study aims to serologically identify patients with presumed (n)pAIR through determination of both known and unknown ARAs by autoantibody profiling.
  
  
  METHODS
  An antigen suspension bead array using 188 different antigens representing 97 ocular proteins was performed to detect ARAs in serum samples of patients with presumed (n)pAIR (n = 24), uveitis (n = 151) and cataract (n = 21). Logistic regressions were used to estimate the associations between ocular antigens and diagnosis. Validation of interphotoreceptor matrix proteoglycan 2 (IMPG2) and recoverin antigens was performed by immunohistochemistry and immunoblot, respectively.
  
  
  RESULTS
  Samples of patients with presumed (n)pAIR exhibited a broad spectrum of ARAs. We identified retinal antigens that have already been described previously (e.g. recoverin), but also identified novel ARA targets. Most ARAs were not specific for (n)pAIR since their presence was also observed in patients with cataract or uveitis. High titers of autoantibodies directed against photoreceptor-specific nuclear receptor and retinol-binding protein 3 were more common in patients with presumed (n)pAIR compared to uveitis (p = 0.015 and p = 0.018, respectively). The presence of all other ARAs did not significantly differ between groups. In patients with presumed (n)pAIR, anti-recoverin autoantibodies were the most prevalent ARAs. Validation of bead array results by immunohistochemistry (anti-IMPG2) and immunoblot (anti-recoverin) showed concordant results in (n)pAIR patients.
  
  
  CONCLUSIONS
  Patients with (n)pAIR are characterized by the presence of a broad spectrum of ARAs. The diagnosis of (n)pAIR cannot be based on the mere presence of serum ARAs, as these are also commonly present in uveitis as well as in age-related cataract patients.
authors.affiliation: Department of Ophthalmology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Josianne C
authors.identifier: http://orcid.org/0000-0003-4610-4991
authors.initials: JC
authors.lastname: Ten Berge
authors.affiliation: Department of Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: van Rosmalen
authors.affiliation: Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jacolien
authors.initials: J
authors.lastname: Vermeer
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Hellström
authors.affiliation: SciLifeLab, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lindskog
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Qundos
authors.affiliation: Department of Ophthalmology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Aniki
authors.initials: A
authors.lastname: Rothova
authors.affiliation: Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Marco W J
authors.initials: MW
authors.lastname: Schreurs
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000097:blood*; D006801:Humans; D010257:Paraneoplastic Syndromes / Q000097:blood*; D012164:Retinal Diseases / Q000097:blood*
chemical_list: D001323:Autoantibodies