Diversity in autoimmunity against retinal, neuronal, and axonal antigens in acquired neuro-retinopathy

Grazyna Adamus, Lori Brown, Jade Schiffman, Alessandro Iannaccone

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Purpose: Autoimmune retinopathies and optic neuropathies are complex disorders of the retina and the optic nerve, in which patients develop autoantibodies (AAbs) against retinal and optic nerve proteins. Autoimmunity might significantly influence the outcome of retinal and optic nerve degenerative process but the pathogenic process is not fully elucidated. To better understand the role of AAbs in pathogenicity of these suspected autoimmune visual disorders, we focused on unique AAbs specificities associated with the syndrome to identify their antigenic targets in the optic nerve and retina. Methods: Serum samples were obtained from patients, whose visual disorders were potentially autoimmune in nature, including patients with cancer with possible paraneoplastic syndrome. Autoantibodies were tested against human optic nerve and retinal antigens for specificity by Western blotting and immunofluorescence. Results: Out of 209 tested for anti-optic nerve autoantibodies, 55% showed specific neuronal autoantibodies. The repertoire of anti-optic nerve autoantibodies often differed from anti-retinal antibodies. The major antigenic targets for these antibodies could be divided into four groups. Autoantibodies specific to classical glycolytic enzymes involved in energy production (α and γ enolases, glyceraldehyde 3-phosphate dehydrogenase) also reacted with retinal antigens. Autoantibodies targeted neuronal-specific myelin proteins (MBP, MOG), aquaporin 4, and collapsing response mediator protein 5 reacted with optic nerve antigens. They showed immunostaining of axons and myelin in the optic nerve as determined by double immunofluorescence. Conclusion: We identified novel neuronal autoantigens not previously known to be associated with acquired autoimmune retinopathy and optic neuropathy. Knowledge of the full autoantibody repertoire perpetuating this syndrome is an important first requirement in increasing our understanding of the autoimmune process to facilitate better diagnosis, prognosis, and treatment.

Original languageEnglish (US)
Pages (from-to)111-121
Number of pages11
JournalJournal of Ophthalmic Inflammation and Infection
Volume1
Issue number3
DOIs
StatePublished - Sep 1 2011

Keywords

  • Autoantibodies
  • Autoimmunity
  • Immunofluorescence
  • Neuropathy
  • Optic nerve
  • Retina
  • Retinal degeneration
  • Retinopathy
  • Western blotting

ASJC Scopus subject areas

  • Ophthalmology
  • Infectious Diseases

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