Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin's disease

Neurology. 2003 Jan 28;60(2):230-4. doi: 10.1212/01.wnl.0000041495.87539.98.


Background: Preliminary studies suggested that anti-Tr antibodies identify patients with paraneoplastic cerebellar degeneration (PCD) and Hodgkin disease (HD).

Objective: To extend the clinical-immunologic analysis to 28 patients with anti-Tr antibodies.

Methods: Anti-Tr antibodies were detected by immunohistochemistry. A competitive inhibition assay was used to ascertain if anti-Tr antibodies of different sera identify common epitopes. Anti-Tr immunoglobulin G (IgG) subclass distribution was determined by immunohistochemistry using monoclonal antibodies against human IgG isotypes. Tr immunoreactivity was analyzed in tumor sections using biotinylated anti-Tr IgG.

Results: Median age of the 28 patients was 61 years (range 14 to 75 years) and 22 were male. A cerebellar syndrome was present in 27 patients and a possible limbic encephalitis in one. HD was diagnosed in 25 patients. No tumor was found in three patients; the autopsy of one of them disclosed severe loss of Purkinje cells without inflammatory infiltrates. Anti-Tr antibodies spontaneously disappeared in all patients without tumor and in 10/10 patients after successful HD treatment. Anti-Tr antibodies were absent in the serum but positive in the CSF of two patients. All positive anti-Tr sera inhibited the immunoreactivity of biotinylated anti-Tr IgG. The predominant isotypes of anti-Tr were IgG1 and IgG3. Only 1 out of the 15 HD samples studied presented anti-Tr positivity that was localized in some Reed-Sternberg cells.

Conclusions: This study confirms the strong association between anti-Tr antibodies and PCD associated with HD. Anti-Tr antibodies from different patients recognize similar epitopes. Unlike other antineuronal antibodies, anti-Tr antibodies can be detected in the CSF but not in the serum and may spontaneously disappear during the follow-up, and Tr immunoreactivity is usually lacking in the tumor.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Antigens, CD / analysis
  • Antigens, CD / biosynthesis
  • Autoantibodies / blood*
  • Biomarkers / blood
  • Disease Progression
  • Female
  • Hodgkin Disease / complications*
  • Hodgkin Disease / diagnosis*
  • Hodgkin Disease / immunology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Paraneoplastic Cerebellar Degeneration / complications*
  • Paraneoplastic Cerebellar Degeneration / diagnosis*
  • Paraneoplastic Cerebellar Degeneration / immunology
  • Predictive Value of Tests
  • Purkinje Cells / immunology
  • Purkinje Cells / pathology
  • Rats
  • Reed-Sternberg Cells / immunology
  • Reed-Sternberg Cells / pathology
  • Remission Induction


  • Antigens, CD
  • Autoantibodies
  • Biomarkers