The aim of the study was to search for novel targets of
autoantibodies in patients with paraneoplastic neurological syndromes (PNS). PNS are mediated by immune reactions against
autoantigen(s) shared by the
cancer cells and the nervous system. By serological screening of a rat cerebellum
cDNA expression library using anti-Hu-positive sera from three patients with
paraneoplastic encephalomyelitis (PEM), we identified an open reading frame encoding an
isoform of the BTB-kelch
protein KLHL7. Immunohistochemical studies demonstrated that the KLHL7
protein is expressed in the nuclei of neurones, but not in other tissues including various
cancers. However, the KLHL7
protein was detected in the nuclei of
cancer cell lines.
Antibodies to KLHL7 were detected by an immunoprecipitation assay in sera from 12 of 254 (4.7%) patients with various
cancers and 2 of 170 blood donors (1.2%). None of 50 sera from patients with
multiple sclerosis were positive for KLHL7
antibodies. Sixteen patients with classical PNS and anti-Hu or
anti-Yo antibodies were also negative for KLHL7
antibodies. Seven
cancer patients with KLHL7
antibodies had various signs of neurological disease that could be related to
cancer, whereas the remaining five seropositive
cancer patients had no clinical signs of possible PNS. The present results indicate that KLHL7
antibodies are associated with various
cancers, and in some patients also with neurological disease. Whether KLHL7
antibodies can be used as paraneoplastic markers for PNS remains to be determined.