Hu antigens: reactivity with Hu antibodies, tumor expression, and major immunogenic sites

Ann Neurol. 1995 Jul;38(1):102-10. doi: 10.1002/ana.410380117.


HuD, a human neuronal RNA-binding protein, was the first identified member of a family of antigens that also includes HuC and Hel-N1 (Hu antigens). The serum of all patients with anti-Hu-associated paraneoplastic encephalomyelitis and sensory neuronopathy react with HuD and Hel-N1, but the reactivity with HuC is unknown. In the current study we examined (1) the reactivity of anti-Hu sera with HuD, HuC, and Hel-N1; (2) the expression of HuD, HuC, and Hel-N1 messenger RNA in small-cell lung cancer of patients with and those without paraneoplastic encephalomyelitis/sensory neuronopathy; (3) the correlation between anti-Hu serum reactivity with these three Hu antigens and the type of neurological symptoms; and (4) the major immunogenic sites of HuD. Our findings indicate that all anti-Hu sera react with HuD, HuC, and Hel-N1. However, only HuD is expressed in the small-cell lung cancer tumors, indicating that among the three Hu antigens, HuD appears to play a central role in triggering the anti-Hu immune response. No differences were identified regarding the reactivity of the anti-Hu antibodies with HuD, HuC, and Hel-N1 and the spectrum of neurological symptoms presented by the patients. Study of the major immunogenic sites of HuD resulted in the identification of two major immunodominant regions with at least two distinct epitopes recognized by the serum of all patients with anti-Hu-associated paraneoplastic encephalomyelitis/sensory neuronopathy.

Publication types

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

MeSH terms

  • Adolescent
  • Aged
  • Antibodies / immunology*
  • Base Sequence
  • Carcinoma, Small Cell / genetics
  • Carcinoma, Small Cell / immunology
  • ELAV Proteins
  • ELAV-Like Protein 4
  • Encephalomyelitis / genetics
  • Encephalomyelitis / immunology
  • Epitopes / immunology*
  • Female
  • Gene Expression / immunology*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Nerve Tissue Proteins / immunology*
  • Paraneoplastic Syndromes / genetics
  • Paraneoplastic Syndromes / immunology
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / immunology
  • RNA-Binding Proteins / immunology*
  • Sequence Deletion
  • Tumor Cells, Cultured


  • Antibodies
  • ELAV Proteins
  • ELAV-Like Protein 4
  • ELAVL4 protein, human
  • Epitopes
  • Nerve Tissue Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • RNA-Binding Proteins