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Detection of autoantibodies to the BTB-kelch protein KLHL7 in cancer sera
G Bredholt1, A Storstein, M Haugen
1Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, N-5021 Bergen, Norway.
Abstract:
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.
Insights
Researchers identified the KLHL7 protein as a novel autoantibody target in paraneoplastic neurological syndromes (PNS). KLHL7 antibodies were found in cancer patients, some with neurological symptoms, suggesting potential as paraneoplastic markers.
Area of Science:
- Neuroimmunology
- Oncology
- Molecular Biology
Background:
- Paraneoplastic neurological syndromes (PNS) involve immune responses targeting antigens shared by cancer and nervous system cells.
- Identifying novel autoantigens is crucial for diagnosing and understanding PNS.
- The anti-Hu antibody is a well-established marker for certain PNS.
Purpose of the Study:
- To discover novel autoantibody targets in patients with paraneoplastic neurological syndromes.
- To investigate the role of the BTB-kelch protein KLHL7 as a potential autoantigen in PNS.
Main Methods:
- Serological screening of a rat cerebellum cDNA expression library using sera from paraneoplastic encephalomyelitis patients.
- Immunohistochemical analysis to determine KLHL7 protein expression in neural and cancer tissues.
- Immunoprecipitation assays to detect anti-KLHL7 antibodies in patient and donor sera.
Main Results:
- A KLHL7 protein isoform was identified as a novel autoantibody target.
- KLHL7 is expressed in neuronal nuclei but also detected in cancer cell lines.
- Anti-KLHL7 antibodies were found in 4.7% of cancer patients and 1.2% of blood donors, but not in multiple sclerosis or classical PNS patients.
- Neurological symptoms were present in some anti-KLHL7 positive cancer patients.
Conclusions:
- KLHL7 autoantibodies are associated with various cancers and, in some cases, neurological disease.
- KLHL7 represents a potential novel biomarker for paraneoplastic syndromes.
- Further research is needed to confirm KLHL7 antibodies as reliable paraneoplastic markers for PNS.
