Anti-Neurofilament Antibodies in the Sera of Patients with Small Cell Carcinoma of the Lung and with Visual Paraneoplastic Syndrome1

The sera of patients with small cell carcinoma of the lung (SCCL) and an associated visual paraneoplastic syndrome (VPNS) have high titer immunoglobulins that react with retinal ganglion cells and with cloned lines of the SCCL. The immunoglobulins in the sera of two patients with SCCL and VPNS reacted with at least one common antigen shared by neural cells and cloned lines of the SCCL. The molecular weights of the predominant neural and tumor antigens were 205,000, 145,000, 65,000, and 20,000-24,000 as determined by Western blots. Three of the antigens from neural tissue copurify and comigrate electrophoretically with neurofilament proteins. Polyclonal antibodies prepared against authentic neurofilament proteins react with antigens having molecular weights identical to those of proteins that react with immunoglobulins from the SCCL-VPNS patients. Polyclonal antibodies that were prepared against isolated retinal ganglion cells and that were shown previously to cause the immunoablation of the ganglion cells in vivo reacted most intensely with the 17, 205,000 antigen and weakly with the M, 145,000 and M, 70,000 antigens. Treatment of the Western blots with alkaline phosphatase from Escherìchiacoli did not affect the immunoreactivity between the immunoglobulins and the purified neurofilament proteins. It is pro posed that the immunoglobulins in the sera of patients with SCCL-VPNS may be involved etiologically in the development of the VPNS. Previous studies in our laboratory revealed that the intravitreous injection of polyclonal immunoglobulins, produced in rabbits against large retinal ganglion cells, could cause the immunoablation of these retinal cells in cats (9, 10). The loss of the large ganglion cells in retina and of their projections to the lateral geniculate nucleus was determined by histolÃ3gica! analysis of retinal wholemounts (10) and by electrophysiological studies of the lateral geniculate nucleus (11). The immunoablation of the ganglion cells of the cat retinas, resulting from intravitreal injection of the polyclonal immu noglobulins, is similar in several respects to the visual PNS in the patients with SCCL. The rabbit immunoglobulins that react with the ganglion cells in cat retina also react with bovine brain proteins having molecular weights of 205,000 and 145,000. The retinas obtained from one patient with SCCL and visual PNS exhibited a marked loss of large ganglion cells,5 as did the retinas from the cats. This report describes the characterization of the neurofilament antigens that react with the immunoglob ulins from the patients with SCCL-VPNS. It also presents the hypothesis that the immunoglobulins in these patients may be involved etiologically in the development of the visual PNS.