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MS Chin, RC Caruso, B Detrick, JJ Hooks; Autoantibodies to Transcription Coactivators p75/p52 (LEDGF) Found in Patients with Retinopathy of Unknown Origin . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2213.
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Purpose: Autoantibodies can be useful in diagnosing, monitoring and understanding the underlying pathology of a disease as well as in identifying therapeutic strategies. This study proposes to determine the identity of the antigen(s) generating anti-retinal autoantibodies in a subpopulation of patients with retinopathy of unknown origin. Methods: Sera from patients diagnosed at the NEI with retinopathy of unknown origin were examined by immunohistochemistry for reactivity to retinal proteins. Positive samples were further characterized by Western blot analyses on mouse retina preparations to determine the number and sizes of possible antigen(s). A rat retina cDNA expression library was screened with the positive sera. Reactive phage clones were purified and the insert cDNA sequenced. The sequence obtained was compared to sequences in GenBank to determine the identity of the protein(s). Results: Three out of 8 patients screened by immunohistochemistry for antibodies to retina were positive. Cell types stained included retinal ganglion cells and cells of the inner nuclear layer. Sera from one patient (Patient 1) were reactive with retina at a titer of 640. Patient 1 had no significant past medical history and presented with symptoms of a progressive retinal disease with gradual visual field loss and decline in ERG amplitude over three years. Western blot analyses of mouse retinal proteins with sera from Patient 1 showed reactivity to two protein species, 52 kDa and 75 kDa proteins. Using sera from Patient 1, a rat retina cDNA expression library was screened and positive clones were identified. One of the clones demonstrated 88% identity to lens epithelium-derived growth factor/transcription coactivators p52 and p75/DSF70. Conclusion: Autoantibodies to retinal proteins were detected in a subset of patients with retinopathy of unknown etiology. The identity of one of the antigens responsible for the reactivity was p75/p52/LEDGF/DSF70, which is a protein that is involved in other autoimmune diseases, such as atopic dermatitis and Vogt-Koyanagi-Harada disease. These data suggest that the antibodies identified in this patient (against p75/p52) may contribute to her retinopathy.
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