Hu antigen specificities of ANNA-I autoantibodies in paraneoplastic neurological disease

J Autoimmun. 1999 Dec;13(4):435-43. doi: 10.1006/jaut.1999.0337.


Despite a broad clinical spectrum, paraneoplastic enecephalomyelitis/sensory neuronopathy (PEM/SSN) is characterized by the presence of a common autoantibody, referred to as anti-Hu or type I anti-neuronal nuclear antibody (ANNA-1). The target of these antibodies is a family of four Hu antigens: three (Hel-N1, HuC, HuD) are neural-specific, while the fourth (HuR) is ubiquitous. Here, we have analysed by enzyme-linked immunosorbent assay (ELISA) the immunoreactivity of all four Hu antigens in serum from 75 patients with ANNA-1 autoantibodies and looked for clinical correlations. IgG in all the patients' sera bound to each of the four antigens, and the titers correlated with those of the ANNA-I immunofluorescence assay. Median titers for the neural-specific antigens (range: 56, 892-90,051) were significantly higher than for HuR (36,799). Patients with gastrointestinal dysmotility or subacute sensory neuronopathy had the highest median titers to all four antigens, while patients with sensorineural deafness had the lowest titers. The results indicate a heterogeneous immune response to individual Hu antigens in patients with PEM/SSN, and that the titers to these antigens as a group, rather than individually, correlate with clinical profile. Furthermore, these results suggest that ELISA analysis of a single neural-specific Hu antigen is sufficient for serological screening in PEM/SSN.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Surface / genetics
  • Antigens, Surface / immunology*
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • ELAV Proteins
  • ELAV-Like Protein 1
  • ELAV-Like Protein 2
  • ELAV-Like Protein 3
  • ELAV-Like Protein 4
  • Enzyme-Linked Immunosorbent Assay / methods
  • Humans
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology*
  • Paraneoplastic Syndromes, Nervous System / blood
  • Paraneoplastic Syndromes, Nervous System / immunology*
  • Paraneoplastic Syndromes, Nervous System / physiopathology
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology


  • Antigens, Surface
  • Autoantibodies
  • ELAV Proteins
  • ELAV-Like Protein 1
  • ELAV-Like Protein 2
  • ELAV-Like Protein 3
  • ELAV-Like Protein 4
  • ELAVL1 protein, human
  • ELAVL2 protein, human
  • ELAVL3 protein, human
  • ELAVL4 protein, human
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins