Testing for JC Virus Antibodies for Tysabri-Related PML Risk

A Blood Test to Assess PML Risk Prior to and During Tysabri Therapy

Doctor taking blood from patient
Ariel Skelley/Getty Images

You may have heard of testing for JC virus antibodies in the blood as a way to determine if someone is at a higher risk of developing progressive multifocal leukoencephalopathy (PML) if they take Tysabri (natalizumab) -- a disease-modifying treatment for relapsing MS.

What is the JC Virus?

JC virus is the infectious organism that causes PML, a potentially fatal brain disease. However, many people (about half) have been infected with the JC virus.

It does not cause any disease in people unless conditions are just right -- when the immune system is weakened.

One such situation is in a person with HIV/AIDS. When T-cells (the immune cells that keep the virus contained in healthy individuals) are depleted, this gives the JC virus a chance to cause PML.

In addition, a very small percentage of people who take the MS disease-modifying therapy Tysabri (natalizumab) will develop PML.  In fact, the three risk factors that make a person more likely to develop PML on Tysabri include:

Testing for the JC Virus Antibody

So one way to assess a person's risk of developing PML on Tysabri (before and while they are taking it) is to see if they have been infected with the JC virus. This can be determined by testing for JC virus antibodies (immune system proteins) in their blood.


The challenge here is that many people have been infected with the JC virus, and the vast majority will not develop PML. A positive JC virus antibody tests means that a person has been exposed to the virus, and their risk of developing PML is higher than a person who has a negative test for the JC virus antibody.

But a positive test (either prior to or during Tysabri therapy) is not a contraindication to taking Tysabri. Instead, it means a closer discussion with your neurologist about the risks and benefits of taking Tysabri (a beneficial MS disease-modifying therapy relapsing) versus other therapies for your MS health -- every person is different. 

Also, a negative test for JC virus antibodies does not mean that a person will never get PML, as they may become infected with JC virus in the future. In addition, the test to detect JC virus antibodies is not perfect -- there is a small chance of false-negatives (about 3 percent). This means that a person has JC virus antibodies, but the blood test results report they do not.

This is one reason why testing for the JC virus antibodies is done prior to starting Tysabri and repeated at six months (sometimes more) intervals while a person is taking Tysabri. Repeat testing at regular intervals is important because you can turn positive to the JC virus. In fact, you may have a higher chance of turning positive when taking Tysabri compared to the general population, according to a 2016 study in Neurology: Neuroimmunology & Neuroinflammation

What if a Person Tests Positive for the JC Virus and Takes Tysabri?

If a person tests positive for the JC virus, he or she will have extra close monitoring for PML, even for the six months after Tysabri therapy is discontinued.

Monitoring for PML includes watching closely for symptoms caused by PML (which are variable and are similar to MS) but may include one or more of the following:

  • gradual weakness on one side of the body
  • clumsiness
  • vision changes
  • personality changes
  • problems with thinking, memory, and orientation leading to confusion

Bottom Line

The JC virus antibody test can be helpful in determining who is at a higher risk for developing PML prior to and while taking Tysabri (natalizumab). Tysabri is an effective MS therapy, but the decision to take it is unique for every person. As always, have informed conversations with your neurologist about your MS therapy.


Clifford, D.B., De Luca, A., Simpson, D.M., Arendt, G, GIovannoni, G., Nath, A. (201). Nataulizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: lessons from 28 cases. Lancet Neurology, Apr; 9(4):438-46.

Gorelik, L., et al. (2010). Anti-JC virus antibodies: implications for PML risk stratification. Annals of Neurology, Sep;68(3):295-303.

Koralnik, I.J. Progressive multifocal leukoencephalopathy: Epidemiology, clinical manifestations and diagnosis. UpToDate. Accessed January 2011.

National Institute of Neurological Disorders and Stroke (NINDS). NINDS Progressive Multifocal Leukoencephalopathy Information Page.

National MS Society. Disease-Modifying Therapies

National MS Society. Study shows that people with MS taking Natalizumab develop antibodies to the JC virus a higher than normal rates, emphasizing need for regular monitoring

Schwab, N. et al. (2016). Therapy with natalizumab is associated with high JC seroconversion and rising JCV index values. Neurology: Neuroimmunology & Neuroinflammation, Feb; 3(1): e195.

Continue Reading