Scientists develop assay to detect anti-agrin antibodies in MG
Cell-based test reveals antibodies in MG patients' blood, researchers say
Scientists in Korea have developed a cell-based test that can be used to detect antibodies against agrin, a protein involved in nerve-muscle communication that is sometimes targeted by harmful autoantibodies in people with myasthenia gravis (MG).
The researchers said they validated the test “and have demonstrated that this [cell-based assay] can identify agrin [antibodies] in the [blood] of patients with MG.”
Their study, “Development and Application of a Cell-Based Assay for Detecting Anti-Agrin Antibodies Associated With Myasthenia Gravis,” was published in the Journal of Clinical Neurology.
MG is an autoimmune disease in which self-reactive antibodies disrupt the communication between nerve and muscle cells. The most common types of MG-causing antibodies target acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK), two proteins that play important roles in the communication between nerve and muscle cells.
Agrin is another protein that is important for that process. Recent studies have indicated that some people with MG have antibodies targeting this protein. However, because screening for these antibodies is not yet part of routine clinical practice, few studies have looked for anti-agrin antibodies in MG, and “little is known about the characteristics of patients with [anti-agrin positive] MG,” wrote the researchers, from Yonsei University in Korea.
Fluorescent colors show antibodies
In order to study anti-agrin antibodies, it’s necessary to have a test that can reliably detect them. Seeking to foster more research on these antibodies, the scientists set out to create such a test.
The test they devised works by engineering cells in a dish to express, or produce, high levels of a version of agrin that is tagged with a fluorescent green molecule. The cells are then exposed to blood samples taken from MG patients. If there are anti-agrin antibodies in the blood, they will bind to agrin in the engineered cells. Researchers can then label anti-agrin antibodies with a red fluorescent color and look at cells under a microscope to see if the two colors appear in the same place. If they do, it means that there are anti-agrin antibodies in the patient’s blood sample.
After conducting a series of proof-of-concept tests to confirm that the assay worked as intended, the researchers used their assay to screen 340 blood samples from people with MG, as well as dozens of samples from people with other neurological diseases, and healthy controls.
The scientists detected anti-agrin antibodies in samples taken from two MG patients, one of whom was positive for anti-AChR antibodies and another who tested positive for anti-MuSK antibodies. No anti-agrin antibodies were detected in samples taken from people with conditions other than MG, or from healthy controls.
Because there were few patients with anti-agrin antibodies, the researchers weren’t able to draw any firm conclusions about the role these antibodies may have in MG. The scientists called for further studies with larger sample sizes to explore the clinical relevance of anti-agrin antibodies.
“The clinical value of agrin [antibodies] is not yet understood owing to the insufficient numbers of studies and patients associated with the low prevalence of agrin-[antibody]-positive MG, and so international collaborations may be necessary to accurately identify its clinical features,” they wrote.
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