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Mayo’s Vanda Lennon, M.D., Ph.D., leads research that identifies biomarker for brain and spinal cord inflammation

Mayo Clinic research has identified a new biomarker for brain and spinal cord inflammation. Vanda Lennon, M.D., Ph.D. (N ’78), and colleagues identified the new biomarker – an antibody – in spinal fluid and blood serum of patients with a neurological disorder called autoimmune meningoencephalomyelitis. In this disorder, the autoantibody targets a protein called glial fibrillary acidic protein within astrocytes in the brain and spinal cord.

Old test yields new discovery

The discovery was made with a test developed in the 1960s. “The test we used has been a tremendous tool of discovery and diagnostic tool for the last 35 years since I set up this lab,” says Dr. Lennon. “It had fallen out of fashion about 20 years ago when we were encouraged to use modern molecular techniques. We certainly use molecular techniques, which are important validation steps, but we did not give up the valuable older technology as a component of our 21st-century screening protocol to detect informative autoantibodies. In the process, we have continued to discover new autoantibodies of clinical importance.”

The process in which the biomarker was identified involves applying a patient’s serum or spinal fluid to thin secretions of mouse tissues. If an autoantibody is present, it will stick to the targeted tissue. After the serum or spinal fluid is washed off, a probe in the form of another antibody is applied to the tissue to detect any human antibody that remains bound to the tissue. The probe antibody is tagged with a fluorescent dye. When viewed under a fluorescence microscope, the tagged antibody shows the location of the bound human autoantibody, revealing the cells targeted by the immune system. In this case, the pattern of binding to mouse brain tissue resembles the pattern of abnormalities seen in MRI images of the patient’s brain and spinal cord.

A positive test for glial fibrillary acidic protein autoantibody should bring the correct diagnosis earlier and hasten the most appropriate treatment. According to Dr. Lennon, the disease reverses rapidly with therapy directed at the immune system.

Proxy marker of more aggressive compound

Diagnosis and treatment of patients is expected to improve in another important way. Dr. Lennon says the team has identified about 103 patients with the biomarker, and about one-third of them have an unsuspected cancer in a remote part of the body. The team suspects that because cancer cells and the nervous system use some of the same mechanisms for communication, the immune response that is attacking a cancer also is causing collateral damage to the nervous system in the process.

“It appears that the antibody does not itself cause the brain inflammation,” she says. “It is a proxy marker of a more aggressive component of the immune system called killer T cells, which target the same brain protein.”

The next steps are to verify the glial fibrillary acidic protein autoantibody’s diagnostic performance. Mayo Clinic’s Neuroimmunology Laboratory anticipates offering this test for diagnostic purposes.

The research was published in the November issue of JAMA Neurology.



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