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Exp Mol Pathol. 2009 Dec;87(3):195-203. doi: 10.1016/j.yexmp.2009.08.003. Epub 2009 Sep 8.

Molecular biomarkers for autoimmune retinopathies: significance of anti-transducin-alpha autoantibodies.

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Casey Eye Institute, Department of Ophthalmology, School of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.


Autoimmune retinopathies (AR) are uncommon retinal degenerations with vision loss associated with unique clinical symptoms and findings and with serum anti-retinal autoantibodies. The experimental and clinical studies corroborate that autoantibodies in high titers can penetrate into the retina affecting function of the target antigens, which leads to retinal dysfunction and degeneration. Anti-recoverin and anti-enolase alpha-enolase autoantibodies were more frequently recognized in AR but autoantibodies with other specificities have also been documented, indicating immunological heterogeneity. Our goal was to examine the associations of anti-retinal autoantibodies with retinopathy in order to identify molecular biomarkers for better diagnosis and prognosis of retinopathies. In these studies we examined 39 patients (10 with cancers) of average age of approximately 57 years old with sudden onset of unexplained progressive vision loss and the presence of circulating serum autoantibodies against 40-kDa retinal protein. The patients presented the retinal phenotype characterized by defects in visual fields and reduced scotopic ERG responses. Anti-40-kDa autoantibodies had specificity to the amino terminus of transducin-alpha. None of the normal subjects' sera had anti-40-kDa autoantibodies. In conclusion, the clinical phenotype of patients with anti-transducin-alpha autoantibodies differed from other phenotypes of AR. These patients, often women at a ratio approximately 2:1, had defects in rod (scotopic) photoreceptor function and typically did not have cancers, whereas the anti-recoverin phenotype is associated with cancer and severe loss of rod and cones function, and anti-enolase retinopathy typically presents with cone dysfunction and is equal in cancer and non-cancer patients. Our studies suggest that anti-transducin autoantibodies can serve as molecular biomarkers for retinal phenotypes and could be used for progression of retinal dysfunction and degeneration.

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