JC virus and PML

The JC virus is a common infection completely unrelated to MS. Between 40-90% of the general population have been exposed to JC virus. You are unlikely to know if you have been infected, as JC virus causes no symptoms, and is normally kept under control by the immune system.

However, if your immune system is then weakened, the JC virus can reactivate. It can then cause serious and potentially fatal inflammation and damage to the brain known as progressive multifocal leukoencephalopathy (PML). 

Treatment with some of the more effective disease modifying drugs, in particular Tysabri (natalizumab), but also very rarely Gilenya (fingolimod) and Tecfidera (dimethyl fumarate) can increase the risk of developing PML. This is because they operate by suppressing your immune system. 

Currently, we do not know why some people with JC virus develop PML and others do not. Although smoking is a risk factor for other viral and bacterial infections, it does not seem to influence JC virus. It is likely that your age, genetic makeup, and immune function affect your risk of developing PML, but research is under way to confirm this.

Testing for JC virus

When you are infected with JC virus you develop antibodies to the virus. A test called Stratify JCV can detect the presence and level of these antibodies in your blood, which can be used to estimate your risk of developing PML. 

Before you start treatment with Tysabri you will be given this blood test at the start of your treatment, as well as an MRI. You should then repeat the blood test every six months. The test is repeated even if you are negative, as you could become infected with JC virus at any time. If a previous blood test found low levels of JC virus infection, you should also continue to have blood tests as the virus level can increase. 

If the test finds no JC virus in your blood sample, (often referred to as JCV negative) the risk of PML is very small (less than 1 in 10,000).

If the blood test finds JC virus (JCV positive), this indicates that you are at a higher risk of developing PML, although for most people the risk is still small. 

Your risk of developing PML also depends on whether you have previously taken other drugs that suppress the immune system (for example, azathioprine, cyclophosphamide, mitoxantrone or methotrexate), how long you have been taking Tysabri (especially over two years) and the amount of JC virus antibody (titre) in your blood. With different combinations of these factors the risk of developing PML ranges from less than 1 in 10,000 up to 1 in 125. You can estimate your risk of developing PML using this guide developed by the MS team at Barts.

The test does not indicate if you will or will not get PML. The test indicates your relative level of risk, information which can help you and your MS team make decisions about treatments and whether to switch to another DMD.

Progressive Multifocal Leukoencephalopathy (PML)

Progressive multifocal leukoencephalopathy (PML) is a rare viral disease of the brain. Like multiple sclerosis, PML damages nerves by demyelination, and causes some similar symptoms, such as weakness, visual problems, impaired speech and cognitive problems. If left untreated, PML can quickly become very serious, and often fatal. Even if it is caught early, it can cause severe and permanent disability.

PML is seen in people with HIV1 infection, and those on immunosuppressive drugs for organ transplants, cancer or autoimmune diseases like MS. It is associated with drugs and conditions that suppress the immune system and allow the JC virus to reactivate, causing inflammation and damage in the brain. The greatest risk is for those who have had very low levels of lymphocytes (a type of white blood cell) for an extended period of time.​

If you are identified as being at a higher risk, your health will be carefully monitored for any warning signs of PML. This could mean more frequent blood testing to check your virus and white blood cell levels, or MRI scans to detect PML at an early stage.

If you start taking Tysabri you will be informed of the early signs and symptoms of PML and advised to report any new or worsening symptoms, even if you think you are having an ordinary relapse. If PML is suspected at any point during treatment, the drug will be discontinued immediately and further tests carried out.

The usual way to treat PML is to flush out the Tysabri out from your body and allow your immune system to fight the JC virus infection in your brain. This is achieved with plasma exchange which involves a series of blood transfusions. 

Further advice has been published for health professionals concerning monitoring for PML.

Find out more

Plavina T, et al.
Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy.
Annals of Neurology 2014;76(6):802-12.
Full article (link is external)
Sorensen PS, et al.
Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab.
Multiple Sclerosis 2012 Feb;18(2):143-52.
Summary (link is external)
Major EO, et al.
Pathogenesis of progressive multifocal leukoencephalopathy and risks associated with treatments for multiple sclerosis: a decade of lessons learned.
Lancet Neurol. 2018 May;17(5):467-480.
Summary (link is external)
Auer M et al.
Smoking is not associated with higher prevalence of JC virus in MS patients.
Eur J Clin Microbiol Infect Dis. 2018 May;37(5):907-910
Summary (link is external)
Mills EA and Mao-Draayer Y
Understanding Progressive Multifocal Leukoencephalopathy Risk in Multiple Sclerosis Patients Treated with Immunomodulatory Therapies: A Bird's Eye View.
Front Immunol. 2018 Feb 2;9:138
Full article (link is external)
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