CRMP-5 neuronal autoantibody: Marker of lung cancer and thymoma-related autoimmunity

We have defined a new paraneoplastic immunoglobulin G (IgG) autoantibody sp ecific for CRMP-5, a previously unknown 62-kd neuronal cytoplasmic protein of the collapsin response-mediator family. CRMP-5 is in adult central and p eripheral neurons, including synapses, and in small-cell lung carcinomas. S ince 1993, our Clinical Neuroimmunology Laboratory has detected CRMP-5-IgG in 121 patients among approximately 68,000 whose sera were submitted for st andardized immunofluorescence screening because a subacute neurological pre sentation was suspected to be paraneoplastic. This makes CRMP-5 autoantibod y as frequent as PCA-1 (anti-Yo) autoantibody, second only to ANNA-1 (anti- Hu). Clinical information, obtained for 116 patients, revealed multifocal n eurological signs. Most remarkable were the high frequencies of chorea (11% ) and cranial neuropathy (17%, including 10% loss of olfaction/taste, 7% op tic neuropathy). Other common signs were peripheral neuropathy (47%), auton omic neuropathy (31%), cerebellar ataxia (26%), subacute dementia (25%), an d neuromuscular junction disorders (12%). Spinal fluid was inflammatory in 86%, and CRMP-5-IgG in 37% equaled or significantly exceeded serum titers. Lung carcinoma (mostly limited small-cell) was found in 77% of patients; th ymoma was in 6%. Half of those remaining had miscellaneous neoplasms; all b ut two were smokers. Serum IgG in all cases bound to recombinant CRMP-5 (pr edominantly N-terminal epitopes), but not to human CRMP-2 or CRMP-3.