Antibody to CCDC104 is associated with a paraneoplastic antibody to CDR2 (anti-Yo)

Abstract

Patients with cancer may develop paraneoplastic neurological syndromes (PNS) in which onconeural antibodies are important diagnostic findings. 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 identified patients with Yo antibodies who also had antibodies to an uncharacterized protein called coiled-coil domain-containing protein 104 (CCDC104). We found a significant association between CCDC104 and Yo antibodies (4 of 38, 10.5%), but not other onconeural antibodies (0 of 158) (P = 0.007, Fisher's 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.

Fig. 1

Western blot of rat cerebellum extract probed with various sera. a Yo serum with an additional 39 kDa band used for cDNA library screen. The 52 kDa band represents the CDR2 protein. b Yo serum without 39 kDa band. c Blood donor as negative control. d Rabbit anti-CCDC104. e Preimmune rabbit serum as negative control

Fig. 2

Immunoblot of human and rat tissue probed with rabbit CCDC104 antibody. a Human tissue. 1 brain, 2 heart, 3 small intestine, 4 kidney, 5 liver, 6 lung, 7 skeletal muscle, 8 testis, 9 spleen, 10 pancreas, 11 ovary. b Newborn rat brain. 1 frontal cortex, 2 posterior cortex, 3 cerebellum, 4 hippocampus, 5 olfactory bulb, 6 striatum, 7 thalamus, 8 midbrain, 9 entorhinal cortex, 10 pons, 11 medulla, 12 spinal cord. The arrow indicates the CCDC104 39 kDa protein

Fig. 3

Indirect immunofluorescence of neuroblastoma cells stained with rabbit CCDC104 antibody. a The CCDC104 antibody mainly stains the nucleus, but also parts of the cytoplasm. b Anti-CCDC104 and DAPI nuclear staining