— British Data Highlights the Interplay Between Environmental and Genetic Factors

The risk of new-onset systemic lupus erythematosus (SLE) substantially increases with exposure to common air pollutants, especially among those with a known genetic predisposition, according to data from the U.K. Biobank study.

An analysis involving approximately 460,000 individuals from this British healthcare database revealed that higher estimated exposure to particulate matter and nitrogen oxides increased the likelihood of developing SLE by 18%-27% per quartile, as noted by Jian Yang, PhD, from China Three Gorges University, and colleagues.

Furthermore, individuals with known high genetic risks and who were subjected to elevated levels of four prevalent pollutants — specifically PM2.5 and PM10 (particulate matter at 2.5 μm or less and 10 μm or less, respectively), nitrogen dioxide (NO2), and total nitrogen oxides (NOx) — exhibited a significantly enhanced risk of SLE. The increased risk ranged from 316% to 461% compared to those with both low genetic risk and low pollutant exposure, as reported in Arthritis & Rheumatology.

A significant proportion of this elevated risk can be attributed to genetic predisposition. Those in the high genetic risk category faced around four times the usual risk of developing lupus, even in low pollution environments. In contrast, individuals with low genetic risk but high pollution exposure demonstrated smaller increases in risk (30%-90%), and these results were often statistically insignificant or borderline.

Despite this, confidence intervals in the study were notably wide, with only 399 cases of SLE identified among the 460,000 study participants during a median follow-up of 11.8 years.

Given these findings, Yang and colleagues expressed caution in interpreting their data. They emphasized the need for further investigation, writing, “Additional cohort studies are essential to further explore the connection between specific pollutants and SLE onset.”

They also pointed out that understanding the biological mechanisms underpinning the link between pollution and SLE development remains crucial, cautioning that “correlation does not imply causation” and calling for more research to establish clear causal links.

Nevertheless, the team viewed their results as meaningful, suggesting that their work sheds light on critical environmental factors contributing to autoimmune conditions. “Our findings underscore the importance of developing stringent air quality standards to limit exposure to harmful pollutants and reduce the risk of SLE," they concluded.

Their research adds to a growing body of evidence pointing to environmental elements, including air pollution, as significant contributors to SLE. However, Yang and colleagues noted that many prior studies focused on short-term exposure and outcomes, such as lupus flare-ups and hospital admissions, rather than first-time SLE diagnosis. Studies investigating new-onset lupus have been limited, primarily conducted in Taiwan. The authors stressed the importance of assessing the relationship between air quality and lupus in Europe, where pollution levels are relatively lower.

This latest analysis was based on data from the U.K. Biobank, a long-term project tracking the health of roughly 500,000 British participants who were first enrolled between 2006 and 2010. In addition to health questionnaires and physical examinations, the Biobank collects tissue samples that enable genetic studies.

The researchers estimated participants’ exposure to the four pollutants based on average annual concentrations from 2010, drawing on several years of monitoring data. For each pollutant, participants were stratified according to quartiles of exposure. Median values for each pollutant were reported as follows:

• PM2.5: 9.93 μg/m3
• PM10: 19.16 μg/m3
• NO2: 28.11 μg/m3
• NOx: 42.26 μg/m3

Participants’ polygenic risk scores for SLE were calculated, dividing the population into tertiles representing low, medium, and high genetic risk, based on previously completed genome-wide association studies.

The researchers adjusted their analysis for a comprehensive set of variables, including age, sex, ethnicity, income level, employment status, smoking and alcohol habits, and body mass index.

The average age of participants at baseline was around 57, which the investigators acknowledged as a limitation, given that SLE typically manifests in younger individuals. About half of the participants were women, and over 90% were white.

Yang’s team also analyzed pollution levels as a continuous measure and found that the link between exposure and SLE risk was not always linear. Specifically, a plateau effect was observed for PM2.5 and NOx, where risk between low and moderate exposure levels was marked, but higher exposure did not result in further risk increases. In contrast, a more linear relationship was noted for PM10 and NO2.

The study had its limitations, including the small number of SLE cases, its focus on middle-aged participants, and the sample’s voluntary participation in the Biobank — potentially skewing it towards a more health-conscious group. Additionally, pollutant exposure estimates, which were based on annual averages, may not fully represent individuals' actual exposure. Furthermore, other potential confounding exposures, such as ozone or silica dust, were not considered.

Disclosures

Yang and his co-authors declared no conflicts of interest.

Primary Source

Arthritis & Rheumatology

Source Reference: Xing M, et al "Air pollution, genetic susceptibility, and risk of incident systemic lupus erythematosus: a prospective cohort study" Arthritis Rheumatol 2024; DOI: 10.1002/art.42929.