The photoreceptor cell-specific nuclear receptor is an autoantigen of paraneoplastic retinopathy.
OBJECTIVE
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.
Eichen
J G
JG
Department of Neurology and Laboratory of Neuro-Oncology, University of Arkansas for Medical Sciences and the Arkansas Cancer Research Center, Little Rock, Arkansas 72205, USA.
Dalmau
J
J
Demopoulos
A
A
Wade
D
D
Posner
J B
JB
Rosenfeld
M R
MR
D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D015153:Blotting, Western; D002417:Cattle; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000150:complications; D057093:Orphan Nuclear Receptors; D010257:Paraneoplastic Syndromes / Q000209:etiology / Q000276:immunology*; D020419:Photoreceptor Cells, Vertebrate / Q000276:immunology*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology*; D012164:Retinal Diseases / Q000209:etiology / Q000276:immunology*; D012607:Scotoma / Q000209:etiology; D014157:Transcription Factors / Q000276:immunology*; D014786:Vision Disorders / Q000209:etiology; D014792:Visual Acuity
D001323:Autoantibodies; D001324:Autoantigens; C403073:NR2E3 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors