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Cancer Immunol Immunother (2010) 59:231237
DOI 10.1007/s00262-009-0742-3
ORIGINAL ARTICLE
Antibody to CCDC104 is associated with a paraneoplastic antibody to CDR2 (anti-Yo)
Cecilie Totland Geir Bredholt Mette Haugen Bjrn Ivar Haukanes Christian A. Vedeler
Received: 26 March 2009 / Accepted: 11 July 2009 / Published online: 14 August 2009 Springer-Verlag 2009
Abstract Patients with cancer may develop paraneo-plastic neurological syndromes (PNS) in which onconeural antibodies are important diagnostic ndings. As the functional role of onconeural antibodies is largely unknown, insight gained by identifying associated antibodies may help to clarify the pathogenesis of the PNS. In this study, we identied patients with Yo antibodies who also had antibodies to an uncharacterized protein called coiled-coil domain-containing protein 104 (CCDC104). We found a signicant association between CCDC104 and Yo antibodies (4 of 38, 10.5%), but not other onconeural antibodies (0 of 158) (P = 0.007, Fishers exact test). The prevalence of CCDC104 antibodies was approximately similar in patients with cancer (8 of 756, 1.1%) and in healthy blood donors (2 of 300, 0.7%). CCDC104 antibodies were not associated with PNS, as this was found in only two of the ten CCDC104-positive patients. The CCDC104 protein, whose function is unknown, is expressed in various human tissues, including the brain, and is localized mainly to the nucleus, but is also found in the cytoplasm. The association between Yo and CCDC104 antibodies may indicate functional similarities.
Keywords CCDC104 CDR2 Onconeural antibody
Paraneoplastic neurological syndrome
Introduction
Paraneoplastic neurological syndromes (PNS) are rare side effects of cancer, and can be found in patients with various types of cancer. Onconeural antibodies recognize antigens in the cancer that are similar to neuronal proteins and can be detected both in the serum and in the cerebrospinal uid of patients with PNS. These antibodies are, therefore, of great importance. Specic antibodies are often associated with specic PNS and types of cancer; Hu antibodies are commonly associated with paraneoplastic encephalomyelitis and small-cell lung cancer whereas Yo antibodies are often associated with paraneoplastic cerebellar degeneration (PCD) and ovarian cancer [1]. The detection of onconeural antibodies usually relies on immunohistochemistry and immunoblotting, but we have also developed an in vitro transcription and translation assay that is very sensitive and specic for detecting onconeural antibodies [24].
Some patients with PNS also harbor...