Scientists have discovered a new autoimmune disease that is specifically triggered by testicular cancer. Utilizing a newly developed diagnostic tool, the research revealed how the cancer can cause the immune system to target the brain, bringing on severe neurodegenerative disease.
Neurological diseases are usually tracked by applying a bio-specimen sample from a patient to a tiny slice of brain tissue from a mouse. The pattern of staining subsequently seen under a microscope, caused by antibodies binding to the brain tissue, can be used to determine certain autoimmune diseases.
For about 20 years scientists have identified a specific staining pattern that was only associated with testicular cancer patients who were also suffering symptoms of ataxia, a neurodegenerative condition. However, it was unclear exactly what antibody was causing this specific staining pattern.
A new study appears to have finally solved this long-standing mystery. Using a newly developed form of programmable phage display technology scientists are now able to screen patient samples, tracking 700,000 different antibody targets against all known human proteins.
Analyzing cerebrospinal fluid from a patient with both testicular cancer and unexplained neurological symptoms, the new screening method detected autoantibodies that target a protein called KLHL11. This protein is specifically found in both the testes and some parts of the brain.
It is suspected that the immune system is primed to target this protein once a testicular tumor appears, and then the immune system antibodies follow that protein target up into the brain, subsequently resulting in severe neurological damage. This newly defined autoimmune disease testicular is called cancer-associated paraneoplastic encephalitis.
A paraneoplastic disease is a condition triggered by a cancer somewhere in the body. Joe DeResi, a biochemist working on the new research, believes this new screening technology will help uncover a number of currently unidentified autoimmune conditions.
"This study is the tip of the iceberg," says DeRisi. "We know there are more paraneoplastic autoimmune diseases waiting to be discovered and more people to help."
So far, the researchers have verified the presence of these KLHL11 antibodies in 37 men with both testicular cancer and unexplained neurological symptoms. It is hoped this research can, in the short term, lead to a new specific diagnostic test for this particular biomarker, helping detect those testicular cancer patients with this condition before too much neurological damage is done.
"Early diagnosis is extremely important," suggests Divyanshu Dubey, co-first author on the new research. "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."
The new study is slated to be published in The New England Journal of Medicine.
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