POP66, A PARANEOPLASTIC ENCEPHALOMYELITIS-RELATED ANTIGEN, IS A MARKER OF ADULT OLIGODENDROCYTES

Paraneoplastic neurological diseases are disorders of the central nerv ous system, associated with neuronal degeneration in patients with sys temic cancer, but are not a direct result of the tumor mass or metasta sis. The biological diagnosis of these syndromes is based mainly on th e detection, in the patient's serum and cerebrospinal fluid, of autoan tibodies (anti-Hu, anti-Yo, for example), suggesting an autoimmune ori gin for these disorders. Recently, we described novel autoantibodies ( anti-CV2 autoantibodies) associated with paraneoplastic neurological d isease, which recognize a 66 kDa brain protein. We named this antigen POP66, for Paraneoplastic Oligodendrocyte Protein of 66 kDa molecular weight, as in the adult human, rat, and mouse brain, it is specificall y expressed by a subpopulation of oligodendrocytes. This cell type spe cificity was surprising given the fact that the cell loss in the brain s of patients with anti-CV2 autoantibodies is neuronal. POP66-expressi ng oligodendrocytes are distributed along the longitudinal axis of the brain according to an increasing rostro-caudal gradient, with no posi tive oligodendrocytes being found in the forebrain and the greatest nu mber found in the spinal cord. In addition, in transverse sections of the spinal cord, the distribution of POP66-positive oligodendrocytes f ollows an increasing dorsal-to-ventral gradient, which may be related to different oligodendrocyte precursor pools. In addition, the neurona l loss without demyelination seen in the brains of patients with anti- CV2 autoantibodies, together with the exclusive oligodendroglial expre ssion of POP66 in the adult brain, raises the question of the possible involvement of POP66 in neuron survival via neuron/oligodendrocyte in teractions.