The photoreceptor cell-specific nuclear receptor is an autoantigen of paraneoplastic retinopathy

J G Eichen, J Dalmau, A Demopoulos, D Wade, J B Posner, M R Rosenfeld
Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society 2001, 21 (3): 168-72

OBJECTIVES: To report a novel antibody associated with paraneoplastic retinopathy and to characterize the retinal autoantigen.

METHODS: Immunohistochemistry of rat and human tissues was used to identify antiretinal antibodies. Serologic screening of a bovine retinal cDNA expression library was performed to clone the target antigen.

RESULTS: A 72-year-old woman presented with a 6-month history of progressive visual loss, bilateral central scotomas, light flashes, and night blindness. Visual acuity was 20/40 OD and 20/30 OS. There was generalized loss of retinal pigment and narrow arterioles; discs were normal in appearance. The electroretinogram showed no response. Chest computed tomograph scan demonstrated a right lung mass; biopsy revealed poorly differentiated carcinoma. The patients' serum contained antibodies that immunolabeled nuclei of cells of the outer--and to a lesser extent, the inner--nuclear layer of the adult rat retina. No reactivity was identified with nonretinal adult human or rat tissues. Reactivity was seen in the developing rat embryo. Serologic screening of a bovine retinal library resulted in the isolation of three overlapping clones, encoding a protein highly homologous to the human photoreceptor cell-specific nuclear receptor gene product.

CONCLUSIONS: The target antigen of an antibody associated with paraneoplastic retinopathy is the photoreceptor cellspecific nuclear receptor, a member of a conserved family of nuclear receptors involved in photoreceptor cell development or maintenance.

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