Using advanced technology, scientists have discovered an autoimmune disease that appears to affect men with testicular cancer.
Called "testicular cancer-associated paraneoplastic encephalitis," the disease causes severe neurological symptoms in men. They progressively lose control of their limbs, eye movements, and, in some cases, speech. The disease begins with a testicular tumor, which appears to cause the immune system to attack the brain. Affected men often find themselves misdiagnosed or undiagnosed and appropriate treatment is delayed.
In a study published in The New England Journal of Medicine, the scientists identified a highly specific and unique biomarker for the disease by using a variation of "programmable phage display" technology. Their refined version of this technology simultaneously screens more than 700,000 autoantibody targets across all human proteins.
Using this powerful tool, the researchers evaluated cerebrospinal fluid from a 37-year-old man who had a history of testicular cancer and debilitating neurological symptoms, including vertigo, imbalance and slurred speech. The enhanced phage technology identified autoantibodies targeting Kelch-like protein 11 (KLHL11), which is found in the testes and parts of the brain.
These results were correlated and validated with additional patient samples from the Mayo Clinic. In addition to identifying the cause of this mysterious neurological disease, the results point the way to using this protein biomarker as a diagnostic test for men with testicular cancer-associated paraneoplastic encephalitis.
Mayo Clinic's Neuroimmunology Laboratory annually screens about 150,000 patients for autoimmune neurological diseases by applying patients' biospecimen samples -- serum or cerebrospinal ?uid -- to thin slices of brain tissue from mice. Some patients with autoimmune neurological diseases harbor antibodies that bind to tissue with a specific pattern of staining.
About 20 years ago, Mayo scientists first identified a staining pattern that researchers dubbed "sparkles" because, in a darkroom under a microscope, the patient's sample looked like stars shining dimly in the night sky, theauthor says. The male patient had ataxia -- poor coordination, involuntary eye movements, change in speech -- and turned out to have testicular cancer.
Analyses were conducted on biospecimens of 12 additional men with similar medical histories. All were positive for autoantibodies targeting KLHL11. Using this biomarker signature, 37 patients now have been diagnosed with this paraneoplastic disease, and the scientists believe many more will be diagnosed.
Physicians who suspect a patient may have this form of paraneoplastic encephalitis currently can work with Mayo Clinic to screen for KLHL11. "Early diagnosis is extremely important," the author says. "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."
In an epidemiological assessment included in the study, the prevalence of KLHL11 encephalitis in Olmsted County, Minnesota, home to Mayo Clinic's Rochester campus, was nearly 3 per 100,000 men. Thus, KLHL11 is one of the more common autoimmune encephalitis biomarkers found in Olmsted County, and likely elsewhere in the U.S. and beyond.
https://www.nejm.org/doi/full/10.1056/NEJMoa1816721?query=featured_home
Autoimmune disease associated with testicular cancer discovered!
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