Testing for JC Virus Antibodies for Tysabri

Blood test assesses the risk of MS-related brain disease

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Progressive multifocal leukoencephalopathy (PML) is a rare viral disease of the brain. The risk of PML may sometimes increase in people taking Tysabri (natalizumab), a disease-modifying drug used to treat relapse in people with multiple sclerosis (MS).

PML is caused by the John Cunningham virus (JC virus), a common viral infection that is normally kept under control by the immune system. However, if the immune system is weakened, the virus can reactivate and a serious and potentially life-threatening inflammation of the brain.

To avoid this in people with MS, doctors will perform an antibody test to check for evidence of the virus in a person's blood.

PML and the JC Virus

Research suggests that around 70 percent of the U.S. population is infected with the JC virus. Most people do not know they are infected, and few ever experience illness as a result of the infection.

It is only when a person's immune defenses are compromised that the disease can become "opportunistic." This simply means that the body hasn't the means to defend itself, and the virus exploits the opportunity to cause disease.

We see this in people with advanced HIV infection. With HIV, the virus progressively depletes the immune systems and exposes the body to an array of opportunistic infections (OIs). PML is among the OIs and is classified as an AIDS-defining condition in people with HIV.

With MS, the cause is slightly different. In this case, certain medications can further add to the immune suppression already caused by the disease.

These medications include Tysabri, Tecfidera (dimethyl fumarate), and corticosteroids. Once reactivated, the virus can pass through the blood/brain barrier that separates the central nervous system from the rest of the body.

In the end, a very small percentage of people who take the Tysabri will develop PML and tends to affect those with the following risk factors:

  • Past or current exposure to other immune suppressive drugs (such as azathioprine, cyclophosphamide, dimethyl fumarate, methotrexate, mitoxantrone, or mycophenolate mofetil)
  • Using Tysabri for more than two years
  • Testing positive for JC virus antibody

The JC Virus Antibody Blood Test

Antibodies are defensive immune proteins produced by the immune system in response to a disease-causing pathogen like the JC virus. Each antibody is specific to that pathogen and that pathogen alone. Once produced, that antibody will remain in the body to respond in the event the pathogen returns.

To confirm an infection, we will perform a simple blood test designed to detect specific antibodies. The result of the test can tell us one of two things:

  • A positive result means that a person has been exposed to the virus.
  • A negative result means that there is no evidence of exposure.

The challenge here, of course, is that the majority of people will have been infected with the JC virus. So while a positive result may suggest an increased risk of PML, it is not a contraindication to treatment. Rather, it allows the doctor to look at this and the other risk factors to decide whether Tysabri is appropriate or if other effective options exist

At the same time, the antibody test is not perfect, and there is a three percent chance that it may deliver a false-negative result. This is one of the reasons why the antibody test is performed prior to starting Tysabri and repeated six months later to check for any viral activity.

A Word From Verywell

While the JC virus antibody test is helpful in determining who may be at higher risk of developing PML when using Tysabri, it shouldn't undermine the importance of the drug in treating MS relapse. In the end, the decision whether to use Tysabri or not is an individual one and should be made in consultation with a specialist physician.

If treatment is prescribed, regular follow-ups are essential to not only monitor the effectiveness of treatment but avoid any possible side effects.

Sources:

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

Schwab, N.; Schneider-Hohendorf, T.; Pignolet, B. et al. "Therapy with natalizumab is associated with high JC seroconversion and rising JCV index values." Neurology: Neuroimmunology & Neuroinflammation. 2016; 3(1): e195.

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