Paraneoplastic encephalomyelitis: an update of the effects of the anti-Hu immune response on the nervous system and tumour

The finding that patients with lung cancer and paraneoplastic sensory neuropathy harboured antineuronal antibodies led Wilkinson and Zeromski to hypothesise in 1965 that patients with the “encephalomyelitic form of carcinomatous neuropathy” should be investigated “for the presence of circulating anti-brain antibodies, particularly as lymphocytic infiltration is a prominent feature in these patients”. About 30 years later, the characterisation of the anti-Hu antibody (HuAb)2 3 and Hu antigens has shown that patients with cancer whose serum contains the HuAb have developed an immune response to a family of neuronal RNA binding proteins, that are highly homologous to a drosophila protein (Elav), a protein critical for nervous system development of the fly.4-8 The exact function of the Hu proteins is unknown, but their homology to Elav and their early expression during embryogenesis of the mammalian nervous system9 10 suggest that they are likewise crucial for development and maintenance of the neuronal phenotype. This review updates the effects of the HuAb immune response on the nervous system and the tumour of these patients. About 4% of patients with small cell lung cancer develop a paraneoplastic neurological syndrome (table 1).11 By far the most common disorder is Lambert-Eaton myasthenic syndrome.12 Much less frequent but usually more disabling is an encephalomyelitis and/or a sensory neuronopathy (PEM/SN) associated with HuAb (the anti-Hu syndrome, table 2).13HuAb is detected in serum and CSF by immunohistochemistry, immunoblot of cortical neurons, or recombinant Hu proteins (HuD, HuC, and Hel-N1), or enzyme linked immunosorbent assay (ELISA) of these proteins.4-6 13 14 The most sensitive and specific technique is the immunoblot of recombinant proteins,14 15whereas immunohistochemistry may detect antibody reactivities other than the anti-Hu antibody. We consider that a serum contains high titre of HuAb when the HuD immunoblot reactivity …