Antibodies to a subpopulation of glial cells and a 66 kDa developmental protein in patients with paraneoplastic neurological syndromes.

Abstract

Background-Paraneoplastic neurological syndromes (PNS) are inflammatory disorders that probably depend on autoimmune processes. Several autoantibodies (anti-Hu, anti-Ri, and anti-Yo) have been characterised in PNS and proved to be helpful in the diagnosis. However, these do not account for all the cases and the possibility that other types of antibodies could be detected was investigated. Methods and results-Of 45 patients with PNS whose serum was probed on paraformaldehyde fixed rat brain sections, 11 patients were identified whose serum samples recognised a cytoplasmic antigen in a subpopulation of glial cells in the white matter of adult rat brainstem, cerebellum, and spinal cord that were double labelled with a monoclonal antibody specific for oligodendrocytes. All serum samples reacted with a 66 kDa protein of newborn rat brain on western blot analysis. These antibodies were designated as anti-CV2 antibodies. Only one of the 11 patients had one of the well characterised autoantibodies (anti-Hu). Five patients had cerebellar degeneration, three had limbic encephalitis, two had encephalomyelitis, and one had LambertEaton myasthenic syndrome. The tumours were small cell lung cancer or undifferentiated mediastinal cancer in seven patients, uterine sarcoma in two, and malignant thymoma in two. Among 1061 control serum samples, only two patients had anti-CV2 antibodies. One had small cell lung cancer and the other malignant thymoma. Conclusions-The detection of anti-CV2 antibodies in patients with neurological

Anti-glial nuclear antibody: Marker of lung cancer-related paraneoplastic neurological syndromes

“…The pattern of immunoreactivity of AGNA in newborn and adult rat brain has similarities with that of anti-CV2, also called CRMP5, antibodies observed in patients with various PNS and SCLC (Honnorat et al, 1996;Yu et al, 2001). Both antibodies recognize antigens which are widely expressed in the developing nervous system and then down regulated and expressed in the adult brain only in a subpopulation of glial cells, oligodendrocytes in the case of CV2 antibodies, and neurons.…”

Isolation and Expression Pattern of Human Unc-33-Like Phosphoprotein 6/Collapsin Response Mediator Protein 5 (Ulip6/CRMP5): Coexistence with Ulip2/CRMP2 in Sema3A- Sensitive Oligodendrocytes

“…The results are summarized in Table 1 and described in detail below. The observed distribution was identical to that described previously with anti-CV2 sera (Honnorat et al, 1996(Honnorat et al, , 1998(Honnorat et al, , 1999. In addition, the distribution of Ulip6/CRMP5 mRNA and protein in the adult brain was similar to that described for Ulip2/CRMP2 (Ricard et al, 2000), so Ulip6/CRMP5 and Ulip2/CRMP2 expression patterns were compared in detail in embryonic and postnatal rat brain.…”

“…In paraneoplastic neurological diseases (PNDs), autoimmune neurodegenerative disorders involving the cerebellum and dentate gyrus, some patients develop autoantibodies (anti-CV2 antibodies) that recognize Ulip/CRMP proteins (Honnorat et al, 1999). Intriguingly, although all anti-CV2 sera tested recognized the same protein (Honnorat et al, 1996) and immunolabeled the same postmitotic neural precursors in the developing brain and the same population of oligodendrocytes (Honnorat et al, 1998), a few failed to recognize any of the four known Ulip/CRMPs, suggesting the existence of another member that was the main target for these antibodies. In the present study, we used one of these anti-CV2 sera to clone a fifth human Ulip/ CRMP member, referred to as Ulip6/CRMP5.…”

Anti-Collapsing Response-Mediating Protein-5 Antibody–Positive Paraneoplastic Perioptic Neuritis without Typical Neurological Symptoms

“…6,13,14 CRMP-5 is expressed in the optic nerve, neurons of the central and peripheral nervous systems, oligodendrocytes, and the cytoplasm of SCLC cells. 5,6,10,11,[13][14][15] It has been suggested that autoantibodies generated against the neoplastic CRMP-5 react as a host immune response to normal tissues, resulting in various neuronal disorders.- 6,10,16 In our case, bilateral meningeal enhancement of the optic nerve was evident on MRI, indicating that the main pathogenesis of the optic neuropathy was bilateral perioptic neuritis due to the involvement of oligodendrocytes around the optic nerve. This cause is consistent with preserved central visual acuity, prominent disc swelling, and prompt disappearance of disc swelling in response to the cancer treatment.…”