Ulip/CRMP proteins are recognized by autoantibodies in paraneoplastic neurological syndromes

Anti-CV2 autoantibodies have recently been discovered in patients with para neoplastic neurological diseases (PND). These disorders are associated with neuronal degeneration, mediated by autoimmune processes, in patients with systemic cancer. Anti-CV2 autoantibodies recognize a brain protein of 66 kD a developmentally regulated and specifically expressed by a subpopulation o f oligodendrocytes in the adult brain. Here, we demonstrate that anti-CV2 s era recognize several post-translationally modified forms of Ulip4/CRMP3, a member of a protein family related to the axonal guidance and homologous t o the Unc-33 gene product in Caenorhabditis elegans. The sequence of the hu man Ulip4/CRMP3 was determined and the gene localized to chromosome 10q25.2 -q26, a region mutated in glioblastomas and containing tumour suppressor ge nes. The identification of the Ulip/CRMP proteins as recognized by anti-CV2 sera should provide new insights into the role of Ulip/CRMPs in oligodendr ocytes and into pathophysiology of PND.