Researchers discover disease linked to testicular cancer
Researchers have discovered a new autoimmune disease that is associated with testicular cancer.
Testicular cancer-associated paraneoplastic encephalitis, the disease, appears to begin with testicular tumors which may cause the immune system to attack the brain.
Researchers from Mayo Clinic , the University of California, San Francisco (UCSF), and the Chan Zuckerberg Biohub identified a specific biomarker for the disease using a variation of programmable phage display technology. The technology screened more than 700,000 autoantibody agents across the subjects’ sampled proteins.
UCSF researchers used the tool to assess cerebrospinal fluid from a 37-year-old man who had testicular cancer and neurological symptoms, including slurred speech, vertigo, and imbalance.
The technology identified that the man’s immune system was attacking Kelch-like protein 11 (KLHK11), which is found in the testes, as well as parts of the brain.
The results were repeated using patient samples from Mayo Clinic. Twelve additional men with similar medical histories were analyzed, and all of them were positive for autoantibodies targeting KLHL11.
The researchers have identified the cause of the neurological disease, and that discovery may lead to a diagnostic test, using that protein’s biomarker, for men with testicular cancer-associated paraneoplastic encephalitis.
The disease causes severe neurological problems in afflicted men, including loss of control over limbs, eyes, and sometimes speech. Affected men have been misdiagnosed or underdiagnosed, and treatment for the disease has been delayed.
Searching for 'sparkles'
Mayo Clinic’s Neuroimmunology Laboratory saw evidence of testicular cancer-associated paraneoplastic encephalitis beginning 20 years ago.
The lab screens patients for autoimmune neurological diseases by applying samples to thin slices of brain tissue from mice. Some antibodies adhere to tissue in specific patterns.
In a darkroom, under a microscope, samples from a patient with ataxia (poor coordination, changes in speech, and involuntary eye movements) created a pattern like "sparkles." That patient turned out to have testicular cancer.
The lab occasionally identified the same pattern in patients with ataxia and testicular cancer — but there was no autoantibody target identified, until the UCSF lab identified KLHL11 as the target.
The full findings are now reported in the New England Journal of Medicine .
The co-first authors are Caleigh Mandel-Brehm, Ph.D., a UCSF postdoctoral researcher, and Divyanshu Dubey, M.B.B.S., a Mayo Clinic neurologist and lab medicine physician.
Thirty-seven patients have been diagnosed with the encephalitis, using the biomarker signature, and the researchers believe more will follow.
Mayo Clinic encourages physicians who suspect that a patient has the disease to work with them to screen for KLHL11.
"Early diagnosis is extremely important," Dubey said in a press release. "If we diagnose patients early, we can start them on immunosuppressive medications. The sooner we can prevent this damage from happening, the sooner we can stop the disease progression and the better chance we have for clinical improvement in the patient's life."
Co-authors Thomas Kryzer and Drs. Dubey, Mandel-Brehm, Joe DeRisi, Brian O'Donovan, Vanda Lennon, Andrew McKeon, Sean Pittock and Michael Wilson report a patent pending for KLHL11 autoantibodies as a biomarker of paraneoplastic encephalitis associated with testicular cancer.