POP66, a paraneoplastic encephalomyelitis-related antigen, is a marker of adult oligodendrocytes

Paraneoplastic neurological diseases are disorders of the central nervous system, associated with neuronal degeneration in patients with systemic cancer, but are not a direct result of the tumor mass or metastasis. The biological diagnosis of these syndromes is based mainly on the detection, in the patient's serum and cerebrospinal fluid, of autoantibodies (anti-Hu, anti-Yo, for example), suggesting an autoimmune origin for these disorders. Recently, we described novel autoantibodies (anti-CV2 autoantibodies) associated with paraneoplastic neurological disease, 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 specifically expressed by a subpopulation of oligodendrocytes. This cell type specificity was surprising given the fact that the cell loss in the brains of patients with anti-CV2 autoantibodies is neuronal. POP66-expressing oligodendrocytes are distributed along the longitudinal axis of the brain according to an increasing rostro-caudal gradient, with no positive oligodendrocytes being found in the forebrain and the greatest number found in the spinal cord. In addition, in transverse sections of the spinal cord, the distribution of POP66-positive oligodendrocytes follows an increasing dorsal-to-ventral gradient, which may be related to different oligodendrocyte precursor pools. In addition, the neuronal loss without demyelination seen in the brains of patients with anti-CV2 autoantibodies, together with the exclusive oligodendroglial expression of POP66 in the adult brain, raises the question of the possible involvement of POP66 in neuron survival via neuron/oligodendrocyte interactions.