Scott Montgomery Professor of medical science (clinical epidemiology) Örebro University, Sweden Director of Clinical Epidemiology and Biostatistics Örebro University Hospital, Sweden

Kissing Disease (MONO) Linked to Increased Risk of MS Years Later Interview with:

Scott Montgomery Professor of medical science (clinical epidemiology) Örebro University, Sweden Director of Clinical Epidemiology and Biostatistics Örebro University Hospital, Sweden

Prof. Montgomery

Prof. Scott Montgomery
Professor of medical science (clinical epidemiology)
Örebro University, Sweden
Director of Clinical Epidemiology and Biostatistics
Örebro University Hospital, Sweden What is the background for this study?

Response: Infections have been linked with increased risk of subsequent multiple sclerosis (MS), but it has been suggested this may be because the genetic or other family characteristics of people who go on to develop MS have a more severe response to infections: the infections would be more likely to be recorded in those who would subsequently develop MS, rather than being risk factors for the disease. To address this issue, we performed a large study of 2,492,980 people living in Sweden, and 5,867 of them had a diagnosis of MS after age 20 years.

We identified who had a hospital diagnosis of infectious mononucleosis (caused by Epstein-Barr virus, EBV infection, and also known as glandular fever or the kissing disease). The new study was different from other studies of infection and MS risk, as it compared siblings in the same families. Siblings share much of their genetic make-up and have similar family lives. If glandular fever is associated with later MS when siblings are compared, then it is unlikely that the association is caused by genetics or other family characteristics that make infections worse in people more likely to develop future MS. What are the main findings?

Response: The study found that, when siblings were compared for their infection history, those who had infectious mononucleosis between ages 11 and 19 years were more likely to have an MS diagnosis after age 20 years. This confirms that this infection (and by extension other serious infections in adolescence) as a risk factor for MS, and not because susceptibility to MS makes it more likely someone will have a more severe infection.

The research provided other interesting information about infectious exposures associated with MS risk. Infectious mononucleosis before age 11 years was less of a risk for MS than after age 11 years. The highest risk for MS was seen for infections between ages 11-15 years (around the time of puberty), with the risk dropping with increasing age and almost completely disappearing by age 25 years. Changes in the brain and immune system as people age may help to explain this.

Even though infectious mononucleosis during the teenage years is a risk MS, it can be many years before MS is diagnosed. Many who had the infection between ages 11 and 15 years did not have an MS diagnosis until after they were 30.  This is because the damage to the brain caused by MS develops slowly until it makes someone sufficiently symptomatic to receive a diagnosis of MS. What should readers take away from your report?

Response: Some serious infections during the teenage years – particularly around puberty – are risk factors for MS, even though often MS may not be diagnosed for at least 10 years after the infection.  We believe that severe infectious mononucleosis may represent a greater risk than some other infections as the virus can enter the brain, causing inflammation that may trigger the MS disease process where the body’s own immune system mounts an (autoimmune) attack on the material called myelin that insulates nerves and is vital for their function. Over an extended period, the damage to nerves in the brain and spinal cord increases, leading to disability, often in younger adulthood. It should be noted that MS is not a common disease and the majority of those who had infectious mononucleosis in adolescence will not develop MS. What recommendations do you have for future research as a result of this work?

Response: Research on causes of MS should consider age and severity of infections, not just whether they occurred at any age.  It would be helpful to look for changes in the brain of people who had severe infectious mononucleosis as teenagers, particularly those with a family history of MS, to identify transient or persistent evidence of changes early in the MS disease process, many years before an MS diagnosis would otherwise be made.   


Dr Montgomery reported receiving grants from the UK Social;  and Economic Research Council and Nyckelfonden (medical charity in Sweden) during the conduct of the study and receiving grants from Roche; Novartis International AG; and AstraZeneca; and honorarium for a lecture from Teva Pharmaceutical Industries Ltd; and serving on the advisory board for a study for IQVIA (with payment to Örebro University Hospital) outside the submitted work.

Funding/Support: This study was supported by a grant from Nyckelfonden, and grant ES/R008930/ from the UK Economic and Social Research Council (International Centre for Life Course Studies), and grant 2019-01236 from the Swedish Research Council for Health, Working Life and Welfare.


Xu Y, Hiyoshi A, Smith KA, et al. Association of Infectious Mononucleosis in Childhood and Adolescence With Risk for a Subsequent Multiple Sclerosis Diagnosis Among Siblings. JAMA Netw Open. 2021;4(10):e2124932. doi:10.1001/jamanetworkopen.2021.24932



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Last Updated on October 27, 2021 by Marie Benz MD FAAD