anti-Hu antibody (type-1 ANNA)

Etiology

• associated malignancies
  • small cell carcinoma (most common)
  • neuroblastoma
  • breast cancer
  • ovarian cancer
  • testicular cancer
  • Hodgkin's lymphoma
• associated neurologic disorders
  • sensory & autonomic neuropathies
  • limbic encephalopathy
  • cerebellar degeneration
  • myelopathy
  • motor neuropathy

Epidemiology

• older persons

Pathology

• primarily affects dorsal root ganglion cells
  • lymphocytic infiltration
  • Nageotte nodules
• degeneration of peripheral & central sensory axons fasciculus gracilis severely affected
• autoantibody directed towards 35-40 kD nuclear RNA-binding proteins
• neuronal nuclear antigens
  • HuC (ELAV-3)
  • HuR (ELAV-1)
  • Hel-N1 (ELAV-2)

Clinical manifestations

• paresthesias or dysesthesias generally start distally & move proximally
• early sensory change may involve face
• position & vibration most severely affected
• sensory ataxia
• pseudoathetosis
• early, widespread absence of reflexes
• neuropathy may precede development of carcinoma for > 3 years, more frequently by a few months
• neuropathy often progresses in a subacute fashion
• limbic encephalitis in 10-20% of patients

Laboratory

• anti Hu autoantibodies in serum & CSF

Management

• treatment of underlying neoplasm usually does not effect the neuropathy (exceptions have been noted)
• response to immunosuppression is generally poor

More general terms

• paraneoplastic autoantibody
• antineuronal nuclear antibody (ANNA)

Additional terms

• ELAV-like protein 1; Hu-antigen R; HuR (ELAVL1, HUR)
• ELAV-like protein 2; Hu-antigen B; HuB; ELAV-like neuronal protein 1; nervous system-specific RNA-binding protein Hel-N1 (ELAVL2, HUB)
• ELAV-like protein 3; Hu-antigen C; HuC; paraneoplastic cerebellar degeneration-associated antigen; paraneoplastic limbic encephalitis antigen 21 (ELAVL3, HUC, PLE21)
• paraneoplastic sensory neuropathy