Occurrence of anti-retinal ganglion cell antibodies in patients with small cell carcinoma of the lung

Abstract

This report describes a patient with small‐cell carcinoma of the lung associated with blindness. The serum of this patient was tested for immunoreactivity with retinal sections because there was no evidence of tumor metastasis to the central nervous system and because neuroendocrine cells of the lung share common antigens with retinal neurons. The immunoglobulins in the sera from this patient, from two other patients with small‐cell carcinoma, from two patients with multiple sclerosis and from three controls were reacted with 8 μm thick sections of retina. Dog, cat and human retinal sections were used. Antihuman immunoglobulins that were conjugated to horseradish peroxidase were used as the second antibody to identify the cells which bound the patients' immunoglobulins. A high titer (1:500) antibody level against retinal ganglion cells was found in the patient with small‐cell carcinoma and blindness; the antibody reaction was similar with retina from the three species. The large ganglion cells bound the immunoglobulins of the patients with small‐cell carcinoma and blindness while the immunoglobulins from the control and multiple sclerosis subjects did not bind these cells selectively at high dilutions. It remains to be shown whether these antibodies have an etiologic significance in the development of blindness.

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

“…We have confirmed previous reports that the sera from CAR patients contain autoantibodies that bind to the retina (Keltner et al, 1983;Kornguth et al, 1982;ThirkiU et al, 1987ThirkiU et al, , 1989. We have afffinity-purified the autoantibodies from complex CAR sera to identify the principal, if not sole, retinal antigen as a 26-kD protein.…”

“…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.…”

“…These "remote effects" of cancer, or paraneoplastic syndromes, are of undetermined etiology, although some studies have implicated viral, hormonal or toxic origins (Brain and Norris, 1965;Hawley et al, 1980;Sawyer et al, 1976;Schold et al, 1979). Alternatively, these degenerative diseases may stem from an autoimmune response that is directed towards antigens or epitopes found in both the tumor and specific neurons (Anderson et al, 1988;Keltner et al, 1983;Kornguth et al, 1982). 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).…”

“…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.…”

Clinicopathological Features of Gastric Cancer Cases and Aberrantly Expressed Recoverin

“…CAR is frequently found in patients with small cell carcinoma of lung and other malignancies (Kornguth et al 1982(Kornguth et al , 1986Keltner et al 1983;Buchanan et al 1984;Klingele et al 1984;Grunwald et al 1985), and is clinically characterized with retinitis pigmentosa-like photoreceptor degeneration caused by an autoimmune reaction toward recoverin, a photoreceptor specific calcium binding protein, and other retinal antigens . Recoverin is known to play an important role in the light and dark adaptation by regulating rhodopsin phosphorylation and dephosphorylation in a Ca 2+ -dependent manner (Kawamura 1991;Ohguro et al 1996).…”