Autoimmune basis for visual paraneoplastic syndrome in patients with small cell lung carcinoma. Retinal immune deposits and ablation of retinal ganglion cells

Abstract

Recently, patients with visual paraneoplastic syndrome (VPS) were described, a binocular loss of vision found in patients with small cell carcinoma of the lung (SCCL). The patients have serum antibodies against a small number of discrete antigens which are shared by the retina and small cell carcinoma cells, and which are associated with cells and processes of the ganglion cell layer of the retina. Pathologic findings are presented with regard to the presence of immunoglobulins in, and the nature of the lesions in, the central nervous system of a VPS patient. The patient's blood-brain barrier was shown to be compromised, as demonstrated by the finding of high immunoglobulin levels in the cerebrospinal fluid and immune deposits in the retina. It is further shown that within the central nervous system only the retina and optic nerve show any tissue damage with the specific loss of retinal ganglion cells and their processes. The findings support the hypothesis of an autoimmune cause for this remote effect of cancer.

Metabolic, structural and functional alterations in patients with inherited diseases of the retina

“…This held true also for the peripapillary retinal venular diameter (Grunwald et al. ; Eysteinsson et al. ).…”

Human autoantibodies against desmoplakins in paraneoplastic pemphigus.

“…Passive transfer ofhuman autoantibodies into rodents produces vesicular degradation of optic nerve myelin sheaths (32) and reduction of retinal ganglion cells (33) in vivo. Unlike the cerebellar degeneration syndrome, however, these autoantigens can be extracted both from tumor of both affected and unaffected individuals and from the human small cell lung carcinoma cell line 119 (32,34).…”

Onconeural Versus Paraneoplastic Antigens?

“…After describing the first three lung cancer patients with rapid loss of vision, Keltner et al postulated that autoimmunity plays a crucial role in CAR [56]. The autoimmunity theory was supported by experimental data showing that serum antibodies from lung cancer patients with CAR can recognize certain cell types in retina sections [57][58][59]. After recoverin was identified as an antigen in CAR [60], its expression was shown in many types of cancer [61,62].…”