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CDR2L Is the Major Yo Antibody Target in Paraneoplastic Cerebellar Degeneration

Torbjørn Kråkenes1, Ida Herdlevaer1,2, Margrethe Raspotnig1

  • 1Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Annals of Neurology
|June 1, 2019
PubMed

Insights

Yo antibodies in paraneoplastic cerebellar degeneration (PCD) primarily target the endogenous CDR2L protein, not CDR2. This finding clarifies the major antigen responsible for Yo-mediated PCD pathogenesis.

Area of Science:

  • Neuroimmunology
  • Onconeural antigens
  • Paraneoplastic syndromes

Background:

  • Paraneoplastic cerebellar degeneration (PCD) is a rare neurological disorder.
  • Yo-associated PCD is frequently linked to specific onconeural antibodies.
  • The precise antigen targeted by Yo antibodies remains debated.

Purpose of the Study:

  • To identify the primary endogenous antigen recognized by Yo antibodies in PCD.
  • To differentiate between CDR2 and CDR2L as the main target of Yo antibodies.

Main Methods:

  • Analysis of cerebrospinal fluid and serum from PCD patients.
  • Immunohistochemical staining of neuronal tissue and cancer cell lines.
  • Testing antibody binding to cells transfected with recombinant CDR2 and CDR2L.

Main Results:

  • Yo antibodies demonstrated binding to endogenous CDR2L in neuronal tissues.
  • No significant binding of Yo antibodies to endogenous CDR2 was observed.
  • Yo antibodies showed reactivity with recombinant CDR2 protein used in clinical assays.

Conclusions:

  • CDR2L is identified as the major endogenous antigen targeted by Yo antibodies in PCD.
  • The reactivity with recombinant CDR2 in assays may be due to cross-reactivity or altered protein structure.
  • This clarifies the immunopathogenesis of Yo-mediated PCD.

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