A new biomarker for brain and spinal cord inflammation has been identified by researchers at Mayo Clinic. This discovery could lead to faster diagnosis and treatment of patients.The findings have been published in the JAMA Neurology.
Vanda Lennon and colleagues identified the new
biomarker in spinal fluid and blood serum of patients with a
neurological disorder called autoimmune meningoencephalomyelitis. The
biomarker is an antibody.
‘A newly identified biomarker in spinal fluid and blood serum of patients may lead to faster diagnosis of brain and spinal cord inflammation.’
Antibodies are molecules used by the immune
system to fight infections or cancer. When an antibody is directed
against healthy tissue by a misguided immune system, as it is in this
disorder, it is called an autoantibody.
meningoencephalomyelitis, the autoantibody targets a protein called
glial fibrillary acidic protein within cells called astrocytes that are
found in the brain and spinal cord.
"Headache is a prominent symptom reported by the patients," says Dr.
Lennon, who is senior author on the study. "It is accompanied by
neurological findings of varying severity. Inflammatory cells in the
spinal fluid and MRI images raise suspicion for brain infection, other
inflammatory brain disease or a cancer spreading to the lining of the
Dr. Lennon notes that this disease rapidly reverses with therapy
directed at the immune system, such as prednisone, in contrast to
infections that need antibiotics and cancer that requires aggressive
treatment. A positive test for glial fibrillary acidic protein
autoantibody should bring the correct diagnosis earlier and hasten the
most appropriate treatment.
The glial fibrillary acidic protein antibody biomarker initially was
identified in Mayo Clinic's Neuroimmunology Laboratory, which is within
the Department of Laboratory Medicine and Pathology. The biomarker was
identified using a test developed in the 1960s.
The process involves
applying a patient's serum or spinal fluid to thin sections 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 patients' brain and spinal cord.
"That method has been a tremendous tool of discovery as well as a
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. Well, we certainly do use
molecular techniques, which are important validation steps, but we did
not give up on 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
With the discovery of this biomarker, Dr. Lennon and the team expect
that diagnosis and treatment for patients will improve in another
important way. "At this stage, we've identified about 103 patients,"
says Dr. Lennon. "And about a third of them are turning out to have an
unsuspected cancer in a remote part of the body."
The research 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 is causing collateral damage
to the nervous system in the process.
"It appears from evidence to date that the antibody does not itself
cause the brain inflammation," says Dr. Lennon. "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. At that point, Mayo Clinic's
Neuroimmunology Laboratory anticipates offering this test for diagnostic