Immunohistochemical analysis of anti-Hu-associated paraneoplastic encephalomyelitis

Acta Neuropathol. 2002 May;103(5):509-15. doi: 10.1007/s00401-001-0498-0. Epub 2002 Jan 31.


The precise immune mechanisms of neuronal death in anti-Hu-associated paraneoplastic encephalomyelitis (PEM) are unclear. We performed an immunohistochemical study on postmortem brain tissue from 11 patients with anti-Hu-associated PEM to further characterize the immune reaction and to ascertain possible mechanisms of neuronal death. To analyze inflammatory infiltrates, antibodies against lymphocyte subpopulations (CD3, CD20, CD4, CD8), macrophage and activated microglia (CD68), major histocompatibility complex (MHC) classes I and II (HLA-ABC and HLA-DR), and the intercellular adhesion molecules (ICAM) -1 and -3 were used. Cell death mechanisms were defined using antibodies against the cytotoxic protein TIA-1, the C9neo component of complement, the Fas receptor (CD95) and its ligand, the apoptosis effector activated caspase-3, and the apoptosis inhibitor Bcl-2. A great number of T cells expressing the cytotoxic protein TIA-1 was observed, mainly in clusters around neurons. ICAM-1 immunoreactivity was increased in the neuropil and reactive astrocytes in areas of inflammation within the central nervous system and in satellite cells of pathological dorsal root ganglia surrounding apparently normal sensory neurons. By contrast, Fas, FasL, C9neo, and activated caspase-3 immunoreactivities were negative in pathological areas. Bcl-2 immunoreactivity was found in satellite cells, but not in sensory neurons of normal and pathological dorsal root ganglia. Our data point out to an induction of a cytotoxic, non-apoptotic, neuronal death in anti-Hu-associated PEM. The increased ICAM-1 immunoreactivity may favor the infiltration of lymphocytes in the pathological areas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens / analysis
  • Antigens / immunology
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Cell Death / immunology
  • Central Nervous System / immunology*
  • Central Nervous System / pathology*
  • Central Nervous System / physiopathology
  • Female
  • Humans
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1 / analysis
  • Intercellular Adhesion Molecule-1 / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / immunology
  • Middle Aged
  • Neuroglia / immunology
  • Neuroglia / pathology
  • Neurons / immunology
  • Neurons / pathology
  • Paraneoplastic Syndromes, Nervous System / immunology*
  • Paraneoplastic Syndromes, Nervous System / pathology*
  • Paraneoplastic Syndromes, Nervous System / physiopathology
  • Poly(A)-Binding Proteins
  • Proteins*
  • Proto-Oncogene Proteins c-bcl-2 / immunology
  • RNA-Binding Proteins / analysis
  • RNA-Binding Proteins / immunology
  • T-Cell Intracellular Antigen-1


  • Antigens
  • Antigens, Differentiation, T-Lymphocyte
  • Membrane Proteins
  • Poly(A)-Binding Proteins
  • Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA-Binding Proteins
  • T-Cell Intracellular Antigen-1
  • TIA1 protein, human
  • Intercellular Adhesion Molecule-1