Exposure to high levels of common air pollutants significantly increases the risk of developing new-onset systemic lupus erythematosus (SLE), especially for individuals with known genetic risk markers, as indicated by data from the U.K. Biobank.
An analysis of approximately 460,000 people in the British healthcare database showed that each step up in quartiles for estimated exposure to particulate matter and nitrogen oxides increased the likelihood of developing SLE by 18%-27%, according to Jian Yang, PhD, of China Three Gorges University in Yichang, China, and colleagues.
For those identified as having high genetic risk who also experienced high levels of four major pollutants—PM 2.5, PM 10, nitrogen dioxide (NO2), and any nitrogen oxide species (NOx)—the risk of SLE increased by 316% to 461% compared to those with low genetic risk and pollution exposure, as reported in Arthritis & Rheumatology.
These significant increases were largely driven by genetic risk. Individuals with high genetic risk faced a quadrupled lupus risk even with low exposure to particulates and nitrogen oxides. Conversely, those with low genetic risk and high pollution exposure had an estimated risk increase of about 30%-90%, which was either statistically insignificant or borderline.
Confidence intervals were generally broad, considering that only 399 out of 460,000 people developed SLE during a median follow-up of 11.8 years.
Yang and colleagues advised caution in interpreting the data. “Additional cohort studies are needed to elucidate the relationship between specific air pollutants and the development of SLE,” they wrote. They also emphasized the need to further explore the underlying biological mechanisms linking air pollution exposure to SLE pathogenesis. They noted that a meaningful correlation does not imply a causal association, necessitating more studies to confirm the causal link between air pollution and the incidence of SLE.
Despite this, the researchers felt their findings should be taken seriously. “Our current study provided crucial insights into the environmental factors contributing to autoimmune diseases,” they stated. “Findings can inform the development of stricter air quality regulations to mitigate exposure to harmful pollutants, thereby reducing the risk of SLE.”
Their research adds to a substantial body of evidence suggesting environmental factors, including air pollution, play a role in SLE. However, Yang and colleagues pointed out that much of the existing research focused on short-term exposure data and outcomes such as disease activity and hospitalizations, rather than new-onset lupus. Prior studies on new-onset lupus were limited to Taiwan, making it essential to evaluate this association in Europe, where air pollution levels are significantly lower, according to the authors.
The researchers used data from the U.K. Biobank, a project collecting health records for around 500,000 individuals in Britain who were enrolled between 2006 and 2010. Participants also completed periodic questionnaires and physical exams, and tissue samples allowed for genetic analysis.
One-year average exposures for the four pollutants were estimated for 2010 based on monitoring data from several years around that time. Biobank participants living in areas without regular monitoring were excluded, and pollutant levels were stratified into quartiles.
Polygenic risk scores were calculated for participants and divided into tertiles defining low, medium, and high risks for SLE based on earlier genome-wide association studies. Statistical results were adjusted for potential covariates including age, sex, race/ethnicity, employment, income, smoking and drinking status, and body mass index.
The mean participant age at baseline was about 57, which is a potential limitation as SLE onset typically occurs in young adulthood. Just over half of the participants were women, and over 90% were white.
Yang and colleagues also analyzed pollution exposure as a continuous variable. They found that the association with SLE risk was nonlinear for two of the four pollutants (PM 2.5 and NOx), which showed a plateau effect. Linear associations were seen for PM 10 and NO2.
The study had limitations, including the small number of incident SLE cases, a largely middle-aged sample, voluntary enrollment in the Biobank (potentially indicating a more health-conscious group), and possible variations in pollutant exposure not captured by annual estimates. Confounders such as exposure to other pollutants like ground-level ozone or silica dust were not accounted for.
John Gever served as Managing Editor from 2014 to 2021 and is now a regular contributor.
Yang and colleagues declared no relevant financial interests.