Role of anti-recoverin autoantibodies in cancer-associated retinopathy

Purpose. To examine the retina and test the serum of a patient with cancer-associated retinopathy syndrome who was diagnosed with small cell carcinoma of the lung and experienced unexpected visual loss. Methods. Proteins from normal human retina were extracted, separated by one- and two- dimensional gel electrophoresis, transferred to PVDF membrane, and used for immunostaining. Antibody specificity was determined by use of solid-phase peptides in a solid-phase immunoassay. Results. Histologic examination of the retina showed loss of the photoreceptor cell layer. This finding correlated with the results of clinical (loss of vision) and electrophysiologic (abnormal electroretinograph [ERG]) tests. The patient's serum antibodies specifically recognized recoverin, a protein predominantly found in retinal photoreceptor cells. The patient's serum also labeled some higher molecular weight proteins present in normal lung and other normal tissues, as well as in lung cell carcinoma cell lines. The only other tissue in which immunoreactivity against p23 could be found was the optic nerve. Our data revealed a lack of cross-reactivity between specific anti-recoverin antibodies and lung proteins. The results indicate that the patient serum contains more than one type of antibody activity. The autoantibodies were tested for fine immunospecificity by use of solid-phase peptides in a solid- phase immunoassay. Patient's antibodies reacted with a major determinant located in the recoverin sequence 62-68 (PKAYAQH) and with several minor ones. Conclusion. Based on the fact that the recoverin appears to be distributed in several different cell types, we suggest that this protein may be present in cancer cells and may play a role in the pathogenesis of some cancer-associated retinopathies.