Rubella infection may increase MS risk in unvaccinated people
Finding supports idea that certain infections may trigger MS immune response
Having antibodies against the rubella virus is associated with an increased risk of developing multiple sclerosis (MS) in unvaccinated people, a Swedish study suggests.
The findings show a rubella infection may be a risk factor for MS, reinforcing the hypothesis that certain viral infections may trigger the misleading immune response that drives MS.
“To the best of our knowledge, this is the first report of an association between [rubella virus] and MS in pre-MS samples,” wrote the researchers, who said additional studies will be needed to confirm the association between rubella infection and MS.
The study, “Rubella virus seropositivity after infection or vaccination as a risk factor for multiple sclerosis,” was published in the European Journal of Neurology.
MS is caused by an erroneous immune response that damages healthy parts of the brain and spinal cord. The reason for the immune response isn’t fully understood, but evidence suggests viral infections may be risk factors. Infection with the Epstein-Barr virus (EBV), in particular, is one of the strongest risk factors for the neurodegenerative condition and some studies have found an association between MS and the human herpesvirus-6A. Also, up to 78% of MS patients have antibodies against measles, varicella zoster, and rubella viruses in their spinal fluid.
It’s believed that, due to some similarities between viral and human molecules, the immune system may mistakenly attack nerve cells when trying to fight a viral infection. This “molecular mimicry” is one proposed mechanism that may explain the association between viruses and a greater risk of MS.
The rubella virus has several proteins that share similarities with human proteins. One protein from its envelope, called E2, is similar to myelin oligodendrocyte glycoprotein (MOG), an essential protein in myelin, the fatty coating that covers nerve cells and target of immune responses in MS.
These similarities raise the possibility of a connection between the rubella virus, the immune response against it, and developing MS.
Rubella infection and MS risk
Researchers in Sweden compared blood samples from MS patients and controls collected before the neurological disease’s onset to determine if people who developed MS had signs of a previous rubella infection — determined through the presence of anti-rubella antibodies — before their diagnosis.
“With samples from both the pre-vaccination era and through the different stages of rubella vaccination in Sweden, we explored a unique opportunity to study [the rubella virus] in the field of MS,” the researchers wrote.
The study included blood samples from 670 MS patients and 670 matched controls. In both groups, female patients represented the majority (84%) and the median age was 25.
The researchers tested the samples for the presence of antibodies (seropositivity) that targeted the rubella E1 protein, which the virus uses to infect human cells, and their reactivity. More MS patients (93.7%) had anti-E1 antibodies than healthy controls (88.5%), data showed.
When patients and controls were divided based on their rubella vaccination status, seropositivity was only significantly higher in MS patients than controls in unvaccinated people, in whom the presence of antibodies indicates a previous rubella infection. After adjusting for factors such as antibodies against other viruses and vitamin D levels, unvaccinated MS patients were four times more likely to have rubella antibodies than unvaccinated controls. No significant differences were observed in vaccinated patients after accounting for the same factors.
The presence of antibodies in “unvaccinated subjects (i.e., representing rubella infection) was associated with a higher risk of developing MS,” the researchers wrote. “Molecular mimicry is an attractive hypothesis for a possible mechanism behind these findings.”
The researchers advised caution when interpreting their findings, mainly because the test they used to determine seropositivity can have a lot of false negatives. Also, most of the participants received the combined measles, mumps, and rubella vaccine, adding variables that weren’t evaluated in the study.
“Further serological and epidemiological studies are needed to support our findings,” they wrote.
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