Exposure to PFAS and PCB mixtures linked to higher MS risk
More than just individual substances must be considered to understand effects
- Exposure to "forever chemicals" (PFAS) and PCB metabolites increases multiple sclerosis (MS) risk
- Highest levels of PFAS and PCBs doubled the odds of MS diagnosis
- Complex interaction between genetic factors and environmental contaminants influences MS risk
People exposed to higher levels of certain manufactured compounds that persist in the environment are more likely to be diagnosed with multiple sclerosis (MS), a new study reports.
A higher MS risk was associated with elevated levels of PFAS, also known as “forever chemicals,” and specific metabolites of PCBs, which have been banned in many countries for decades. Exposure to mixtures of PFAS and PCBs, which more closely reflect actual environmental exposures, increases the odds of developing MS even when there were no significant associations with individual compounds, researchers found.
“The results show that when attempting to understand the effects of PFAS and other chemicals on human beings, we need to take mixtures of chemicals into account, not just individual substances, as people are generally exposed to several substances at the same time,” Aina Vaivade, the study’s first author and a PhD candidate at Uppsala University in Sweden, said in a university news story. The study, “Co-exposure to PFAS and hydroxylated PCBs is associated with increased odds of multiple sclerosis,” was published in Environment International.
MS is a chronic autoimmune disease that’s thought to arise from a combination of genetic and environmental factors. The most prominent risk factor for MS is an Epstein-Barr virus infection, but others include being female sex, childhood obesity, smoking, and variations in genes called HLA.
PFAS, a class of manufactured chemicals widely used in industrial and consumer products, are often referred to as “forever chemicals” due to their extreme persistence in the environment. This is a concern because long-term exposure to PFAS has been linked to disruptions in immune function and an increase in inflammation. PCBs are a group of compounds linked to cancer, immune suppression, and neurological toxicity. Although they’ve been restricted or banned in many countries for decades, PCBs can also persist in the environment and degrade to OH-PCBs, which are more toxic than the parent compounds.
Studying effects of mixtures of chemicals on people
A research team led by Kim Kultima, PhD, the senior author of this study and a professor at Uppsala, recently revealed a link between blood levels of certain OH-PCBs and an increased risk of developing MS. PFAS, in turn, were generally associated with a lower risk of disability worsening among MS patients.
Here, Kultima’s team evaluates the risk of MS across individual compounds and mixtures, the effects of different exposure levels, and the impact of MS-associated HLA genes. They measured 24 PFASs and seven OH-PCBs in blood samples from 907 newly diagnosed MS patients and an equal number of healthy people matched by age, sex, and residential area.
Like the previous findings, two OH-PCBs — 4-OH-CB187 and 3-OH-CB153 — were associated with increased odds of MS. A PFAS called PFOS was also linked to a higher likelihood of developing MS in this analysis. These results remained after controlling for lifestyle and genetic risk factors, but only 3-OH-CB153 remained significantly associated with MS risk after adjusting for multiple comparisons to control for significant results that are likely false, that is false positives.
When the researchers investigated further, they discovered that the odds of MS were about double among the 25% of patients with the highest levels of 4-OH-CB187, 3-OH-CB153, and PFOS compared with the group with the lowest levels.
“We saw that several individual substances, such as PFOS and two hydroxylated PCBs, were linked to an increased odds for MS,” Kultima said. “People with the highest concentrations of PFOS and PCBs had approximately twice as high odds of being diagnosed with MS, compared with those with the lowest concentrations.”
Because people are most likely to be exposed to more than one of these compounds in the environment, the researchers conducted a mixture analysis. Here, the combined PFAS and OH-PCB mixture demonstrated a significant association with higher MS odds, as did mixtures of different PFAS and mixtures of distinct OH-PCBs.
Lastly, scientists examined the interplay between MS risk, PFAS and OH-PCB exposure, and six HLA genes with known associations with MS. People carrying the HLA variant B*44:02, which is protective against MS, were at least five times more likely to develop MS across most PFOS exposure levels. In comparison, among those without B*44:02, only the highest exposure to this compound was associated with increased odds of MS.
“This indicates that there is a complex interaction between inheritance and environmental exposure linked to the odds of MS,” Kultima said. “We therefore think it is important to understand how environmental contaminants interact with hereditary factors, as this can provide new knowledge about the genesis of MS and could also be relevant for other diseases.”
The researchers said further studies are needed to investigate the role of PFAS and OH-PCBs in increasing MS risk.
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