Paraneoplastic neurological syndromes with anti-hu antibodies

Abstract

Paraneoplastic neurological syndromes (PNS) are remote effects of cancer that are neither caused by invasion of the tumor or its metastasis, nor by infection, ischemia, metabolic and nutritional deficits, surgery or other forms of tumor treatment.1 PNS cause severe neurological disability and carry a poor prognosis. In PNS patients, various antibodies (Abs) have been found directed at neuronal antigens that are also expressed by the associated tumors in most cases. In 2004, the term ‘well characterized onconeural Ab’ was defined based on (1) Abs for which there are recognisable patterns on routine immunohistochemistry and for which immunoblotting on recombinant proteins must be used to confirm their specificities; (2) the number of cases reported associated with tumours; (3) the description of well characterised neurological syndromes associated with the antibodies; (4) the unambiguous identification of the Abs among different studies, and (5) the frequency of these Abs in patients without cancer.2 These ‘well-characterized’ onconeural Abs are by definition almost exclusively found in patients with cancer and include anti-Hu, Yo, CV2, Ri, Ma2 and amphiphysin.2 Recently, the anti-Tr antigen has been identified as the transmembrane protein Delta/ Notch-like epidermal growth factor-related receptor (DNER). Anti-DNER is thightly associated with Hodgkin lymphoma, and can therefore be considered a ‘well-characterized’ onconeural Ab, although DNER is not expressed by Hodgkin lymphoma.3 Anti-Hu is the most frequent well characterized onconeural Ab and usually associated with paraneoplastic encephalomyelitis and sensory neuronopathy.4 This thesis will focus on the immunopathogenesis of PNS with well-characterized onconeural Abs, in particular those with anti-Hu Abs (Hu-PNS).