Cytotoxic CD8+ T cells and CD138+ plasma cells prevail in cerebrospinal fluid in non-paraneoplastic cerebellar ataxia with contactin-associated protein-2 antibodies

J Neuroinflammation. 2012 Jul 3;9:160. doi: 10.1186/1742-2094-9-160.

Abstract

Objective: The purpose of this paper is to report a patient with otherwise unexplained cerebellar ataxia with serum antibodies against contactin-associated protein-2 (CASPR-2) and provide a detailed description of the composition of cellular infiltrates in the cerebrospinal fluid (CSF) compared to the peripheral blood (PB). CASPR-2 antibodies strongly labeling axons of cerebellar granule neurons have recently been identified in sera from nine patients with otherwise unexplained progressive cerebellar ataxia with mild to severe cerebellar atrophy.

Design: This is a report of a single case.

Methods: The study methods used were neurologic examination, magnetic resonance imaging, fluorodeoxyglucose positron emisson tomography, lumbar puncture and multicolor flow-cytometry.

Results: A 23-year-old Caucasian male presented with a two-year history of a progressive cerebellar and brainstem syndrome. Magnetic resonance imaging (MRI) showed pronounced cerebellar atrophy, especially of the medial parts of the hemispheres and the vermis. Cerebral fluorodeoxyglucose positron emission tomography (FDG-PET) showed pronounced hypometabolism of the whole cerebellum. CASPR-2 antibodies were detected in the serum but not the CSF, and none of the staging and laboratory assessments revealed other causes of progressive cerebellar degeneration. Interestingly, flow-cytometry of the CSF as compared to the PB showed increased fractions of CD138+ plasma cells as well as human leukocyte antigen (HLA)-DR+ CD8+ T cells suggesting that both B cells and CD8+ T cells were preferentially recruited to and activated within the CSF- (and putatively central nervous system (CNS)-) compartment.

Conclusion: We confirm the association of CASPR-2 serum antibodies with cerebellar ataxia and provide the first evidence for a combined humoral and cellular immune response in this novel antibody-associated inflammatory CNS disease.

Publication types

  • Case Reports

MeSH terms

  • Autoantibodies / biosynthesis*
  • Autoantibodies / cerebrospinal fluid
  • Cerebellar Ataxia / cerebrospinal fluid*
  • Cerebellar Ataxia / diagnosis
  • Cerebellar Ataxia / immunology
  • Humans
  • Male
  • Membrane Proteins / cerebrospinal fluid
  • Membrane Proteins / immunology*
  • Nerve Tissue Proteins / cerebrospinal fluid
  • Nerve Tissue Proteins / immunology*
  • Plasma Cells / immunology
  • Plasma Cells / metabolism*
  • Syndecan-1 / cerebrospinal fluid*
  • Syndecan-1 / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*
  • Young Adult

Substances

  • Autoantibodies
  • CNTNAP2 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • SDC1 protein, human
  • Syndecan-1