Cancer-Associated Retinopathy (CAR Syndrome) with Antibodies Reacting with Retinal, Optic-Nerve, and Cancer Cells

Thirkill, Charles E.; Fitzgerald, Paul G.; Sergott, Robert C.; Roth, Alan M.; Tyler, Nancy K.; Keltner, John L.

doi:10.1056/nejm198912073212307

Cited by 218 publications

(92 citation statements)

References 34 publications

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“…1 B). These experiments confirm previous observations that CAR antisera contain autoantibodies that can bind to retinal sites (Grunwald et al, 1985;Keltner et al, 1983;Kornguth et al, 1982;Thirkill et al, 1987Thirkill et al, , 1989.…”

Section: Methodssupporting

confidence: 91%

“…Evidence supporting this connection has been presented in the case of Eaton-Lambert myasthenic syndrome, a disease of the peripheral nervous system, in which the binding of autoantibodies at the neuromuscular junction interferes with the calcium-induced release of neurotransmitter (DeAizpurua et al, 1988;Kim and Neher, 1988;Newsom-Davis, 1985). An autoimmune component also has been suggested in several diseases of the central nervous system, including paraneoplastic cerebellar degeneration (Anderson et al, 1988;Furneaux et al, 1990;Greenlee and Lipton, 1986) and cancer-associated retinopathy (CAR) t (Buchanan et al, 1984;Grunwald et al, 1985;Keltner et al, 1983;Kornguth et al, 1982;Thirkill et al, 1987Thirkill et al, , 1989.…”

mentioning

confidence: 99%

“…An earlier study of CAR also identified a retinal antigen of 65 kD, as well as a low molecular weight protein of'o 20 kD (Grunwald et al, 1985). More recent and extensive studies of CAR have focused on a prominent retinal antigen of ,o23 kD (Keltner et al, 1983;Thirkill et al, 1987Thirkill et al, , 1989. Several of these antisera cross-react with the 68-kD neurofilament protein, and this finding has led to the speculation that autoantibodies associated with retinal , 1989).…”

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confidence: 99%

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A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy.

Polans

Buczyłko

Crabb

et al. 1991

The Journal of Cell Biology

251

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Abstract. Cancer-associated retinopathy (CAR), a paraneoplastic syndrome, is characterized by the degeneration of retinal photoreceptors under conditions where the tumor and its metastases have not invaded the eye. The retinopathy often is apparent before the diagnosis of cancer and may be associated with autoantibodies that react with specific sites in the retina. We have examined the sera from patients with CAR to further characterize the retinal antigen. Western blot analysis of human retinal proteins reveals a prominent band at 26 kD that is labeled by the CAR antisera. Antibodies to the 26-kD protein were affinity-purified from complex CAR antisera and used for EMimmunocytochemical localization of the protein to the nuclei, inner and outer segments of both rod and cone cells. Other antibodies obtained from the CAR sera did not label photoreceptors. Using the affinitypurified antibodies for detection, the 26-kD protein, designated p26, was purified to homogeneity from the outer segments of bovine rod photoreceptor cells by Phenyl-Sepharose and ion exchange chromatography. Partial amino acid sequence of p26 was determined by gas phase Edman degradation and revealed extensive homology with a cone-specific protein, visinin. Based upon structural relatedness, both the p26 rod protein and visinin are members of the calmodulin family and contain calcium binding domains of the E-F hand structure.variety of neurodegenerative diseases are known to be associated with different types of cancer, even though the tumor and its metastases have not invaded the nervous system (Brain and Norris, 1965;Brain and Wilkinson, 1965;

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Section: Methodssupporting

confidence: 91%

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confidence: 99%

mentioning

confidence: 99%

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A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy.

Polans

Buczyłko

Crabb

et al. 1991

The Journal of Cell Biology

251

View full text Add to dashboard Cite

show abstract

“…CAR is characterised by rapid and progressive visual loss and retinal degeneration that occur in association with cancer without direct invasion or metastasis of cancer to the retina (Thirkill et al, 1989). While the mechanism for paraneoplastic degenerative retinopathy has not been fully elucidated, the presence of peculiar antibodies in patients who suffer from this disease suggests that autoimmunity plays an important pathogenic role in the development of CAR (Thirkill et al, 1989(Thirkill et al, , 1993. Recently, the CAR antigen was identified as a 23 kDa photoreceptor protein, recoverin, from the screening of retinal proteins in CAR patients' sera (Polans et al, 1991;Thirkill et al, 1992).…”

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confidence: 99%

“…Recoverin is specifically localised in the photoreceptor cells and participates in the recovery phase of visual excitation and in adaptation to background light (Kawamura, 1994). While the presence of shared epitopes between retina and cancer cells, especially SCLC, had been proposed, such CAR antigen in cancer cells had not been clarified (Thirkill et al, 1989) until quite recently, when Polans et al (1995 demonstrated the specific expression of recoverin in the SCLC from a patient associated with CAR. We have examined the expression of recoverin in various human lung cancer cell lines, including a cell line derived from an SCLC patient with CAR.…”

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confidence: 99%