The role of anti-α-enolase autoantibodies in pathogenicity of autoimmune-mediated retinopathy

Agnieszka Magrys, Thimmappa Anekonda, Gaoying Ren, Grazyna Adamus

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Autoantibodies against α-enolase, a glycolytic enzyme, have been frequently associated with visual loss and retinal degeneration in patients with autoimmune and cancer-associated retinopathy; however their role in the pathogenicity of retinopathy has not been fully explained. Thus, we examined the causative role of anti-enolase antibodies on retinal cells. In the in vitro studies reported here, we found that Enol-1 monoclonal antibody against α-enolase significantly inhibited the catalytic function of enolase, which resulted in the depletion of glycolytic ATP. Enol-1 significantly increased intracellular Ca2+, which led to Bax translocation to the mitochondria, and the release of cytochrome c into the cytoplasm-events that correlated with the initiation of apoptosis. Normal IgG did not induce intracellular calcium or reduce cytosolic ATP. L-type voltage-gated calcium channel blockers (nifedipine, D-cis-diltiazem, and verapamil) were effective in blocking the Ab-induced intracellular Ca2+ rise and induction of Bax. Based on these findings we propose that chronic access of autoantibodies to the retina results in the inhibition of enolase catalytic function, depletion of ATP, and elevation in intracellular Ca2+, leading to deregulation of glycolysis in retinal neurons and their destruction.

Original languageEnglish (US)
Pages (from-to)181-192
Number of pages12
JournalJournal of Clinical Immunology
Volume27
Issue number2
DOIs
StatePublished - Mar 2007

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Phosphopyruvate Hydratase
Autoantibodies
Virulence
Adenosine Triphosphate
Ocular Paraneoplastic Syndromes
Retinal Neurons
Retinal Degeneration
Diltiazem
Calcium Channel Blockers
Glycolysis
Nifedipine
Verapamil
Cytochromes c
Retina
Anti-Idiotypic Antibodies
Mitochondria
Cytoplasm
Immunoglobulin G
Monoclonal Antibodies
Apoptosis

Keywords

  • Apoptosis
  • Autoantibody
  • Autoimmunity
  • Enolase
  • Glycolysis
  • Neuroimmunology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The role of anti-α-enolase autoantibodies in pathogenicity of autoimmune-mediated retinopathy. / Magrys, Agnieszka; Anekonda, Thimmappa; Ren, Gaoying; Adamus, Grazyna.

In: Journal of Clinical Immunology, Vol. 27, No. 2, 03.2007, p. 181-192.

Research output: Contribution to journalArticle

Magrys, Agnieszka ; Anekonda, Thimmappa ; Ren, Gaoying ; Adamus, Grazyna. / The role of anti-α-enolase autoantibodies in pathogenicity of autoimmune-mediated retinopathy. In: Journal of Clinical Immunology. 2007 ; Vol. 27, No. 2. pp. 181-192.
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