CDR2L Antibodies: A New Player in Paraneoplastic Cerebellar Degeneration

Tilo W Eichler,Kibret Mazengia,Tor H Qvale,Anette Storstein,Bjørn I Haukanes,Christian A Vedeler,Mette Haugen,Cecilie Totland,Prasun Datta

doi:10.1371/journal.pone.0066002

Tilo W Eichler, Kibret Mazengia + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0066002

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Journal: PloS one	Publication Date: Jun 18, 2013
Citations: 58	License type: CC BY 4.0

Affiliation: University of Bergen, Haukeland University Hospital

Abstract

ObjectiveYo antibodies are associated with paraneoplastic cerebellar degeneration (PCD). We have characterized Yo sera by measuring CDR2 and CDR2L antibodies and the localization of their antigens.MethodsForty-two Yo sera from patients with paraneoplastic neurological syndromes (PNS), 179 sera from ovarian and 114 sera from breast cancer patients without PNS and 100 blood donors were screened for CDR2 and CDR2L antibodies by radioactive immune assay (RIA). Fluorescence microscopy was also used to determine the presence of CDR2 or CDR2L antibodies by staining of HeLa cells transfected with CDR2 or CDR2L fused to green fluorescent protein (GFP). Confocal microscopy was further used to localize the CDR2 and CDR2L proteins.ResultsRIA showed that 36 of the 42 Yo positive sera contained CDR2 and CDR2L antibodies whereas 6 sera contained only CDR2 antibodies. Five of the ovarian cancer patients had CDR2L antibodies and 4 of the breast cancer patients had either CDR2 or CDR2L antibodies. Only patients with both antibodies had PCD. RIA and staining of transfected cells showed similar results. Yo antibodies were not present in the 100 blood donors. Confocal microscopy showed that CDR2 and CDR2L were localized to the cytoplasm, whereas CDR2L was also present on the cell membrane.InterpretationYo sera usually contain CDR2 and CDR2L antibodies and both antibodies are associated with PCD. Since only CDR2L is localized to the cell membrane it is likely that CDR2L antibodies may be of primary pathogenic importance for the development of PCD.

Highlights

Patients with paraneoplastic cerebellar degeneration (PCD) often harbour Yo antibodies which cross-react with antigens in tumours and Purkinje cells in the cerebellum [1]
Of these 36 sera, 3 were negative by line blot with recombinant cerebellar degeneration-related protein 2 (CDR2) and 5 were negative by immunofluorescence staining of rat cerebellar tissue, with sections treated with the antigen-retrieval protocol
Two CDR2 sera were from the breast cancer materials with no paraneoplastic neurological syndromes (PNS)

Summary

Introduction

Patients with paraneoplastic cerebellar degeneration (PCD) often harbour Yo antibodies which cross-react with antigens in tumours (often ovarian or breast cancer) and Purkinje cells in the cerebellum [1]. Yo antibodies may be associated with other paraneoplastic syndromes such as encephalomyelitis and can be seen with other tumours such as prostate and colon cancer [2]. Purkinje cell death has been shown to occur in rat cerebellar slice cultures after uptake of Yo antibodies [4], the mechanisms involved in the associated Purkinje cell death in PCD are unknown. Yo antibodies react with a 62 kDa protein (454 amino acids), the cerebellar degeneration-related protein 2 (CDR2; Reference sequence NP_001793.1) [1,5]. There are other members of the CDR family, including CDR2L (CDR2-Like, HUMPPA; Reference sequence: NP_055418.2).

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