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Scientists discover autoimmune disease associated with testicular cancer

Newswise Aug 03, 2019

Using advanced technology, scientists at Chan Zuckerberg (CZ) Biohub, Mayo Clinic and UC San Francisco, have discovered an autoimmune disease that appears to affect men with testicular cancer. A biospecimen contained a pattern that researchers have dubbed "sparkling" because of how the sample looks under a microscope. Over time, researchers noticed that the clinical stories of the patients with these samples were the same: they had ataxia and 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 UCSF 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.

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