First of Its Kind Blood Test for Immunocompromised Patients

A doctor speaking with a patient who is in a wheelchair

PHILADELPHIA- Multiple sclerosis patients who have undergone immune-suppressing treatment will soon get a clear picture of how exactly their bodies’ immune systems responded to the COVID-19 vaccine thanks to a new test developed by researchers at the Perelman School of Medicine at the University of Pennsylvania. Typical measures of immune response can be misleading in this group of patients, but this first of its kind test provides a clear picture that can be integrated into the electronic health record, which clinicians can access to counsel patients.

Developed with support from the National Institutes of Health Autoimmunity Center of Excellence at Penn Medicine, the first-in-class test is aimed at examining both antibody and T-cell response to COVID-19 vaccination in patients with multiple sclerosis (MS) who have undergone immune-suppressing anti-CD20 (aCD20) treatment. Caused by the immune system attacking the protective sheath (myelin) that covers nerve fibers, MS can result in symptoms such as muscle pain, spasms, and even paralysis. Typically administered every six months, aCD20 infusions eliminate B-cells, which helps to manage symptoms, but leaves patients’ immune systems weakened.

“MS patients who receive aCD20 infusions often ask their doctor if it’s safe for them to go to something like their grandson’s graduation, or their granddaughter’s wedding,” said Amit Bar-Or, MD, FRCPC, director of the Center for Neuroinflammation and Experimental Therapeutics and chief of the division of MS and Related Disorders, who helped develop the test. “With this new test, our hope is that clinicians will be able to measure the strength of a patient’s complete immune response to the COVID vaccine, and use results to guide decision-making about different activities in their lives.”

The immune system has two parts. The first part, which uses B-cells to produce antibodies, acts like a colander draining water from cooked pasta: antibodies filter out viruses and prevent them from entering the body and infecting a person’s healthy cells. However, antibodies can’t always catch every viral particle, and some get through to cause infection – similar to how pockets of water can remain trapped among pasta when dumped into a colander. The second part of the immune system are T-cells, which hunt down virally infected cells and eliminate them so that the virus can’t spread. They’re the shakes you give a colander to filter the rest of the water from the pasta.

Many patients with MS undergo aCD20 treatment – which depletes the B-cells that contribute to the MS attacks. Because B-cells are responsible for antibody production, patients’ ability to produce antibodies that prevent viruses from entering and infecting a person’s cells is significantly muted when the B-cells are depleted with a CD20 treatment.

The immune response to vaccination is usually evaluated by measuring the amount of antibodies in the blood. While this method can be informative for patients with a healthy immune system, patients who received aCD20 infusions would appear unable to mount an immune response to vaccination when, in reality, research shows that they are actually able to mount a robust T-cell response.

“If a patient mounted a T-cell response to their first vaccine doses, their provider might advise them to schedule a booster prior to an event like a graduation or wedding,” Bar-Or said. “But if they didn’t show a response to previous doses, the provider may explore other prophylactic therapeutics and could advise on other precautions, like wearing an N95 mask and eating outdoors.”

“Right now, the most pressing application of this test is for COVID-19, but the immune system plays such a huge role in how the body fights most illnesses, there’s enormous potential for this test down the line,” said E. John Wherry, PhD, chair of Systems Pharmacology & Translational Therapeutics, who also led the test’s development. “What’s more, many treatments for a range of conditions, like cancer, can weaken a patient’s immune system. We’re hopeful that, in the future, this test could be used widely to measure the ability of patients’ immune systems to fight a variety of illnesses.”

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