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Prolonged smog exposure linked to immune proteins considered precursors to autoimmune disease.
In A Nutshell:
- Canadian researchers found people exposed to the highest levels of PM2.5 air pollution were 54% more likely to test positive for high levels of anti-nuclear antibodies, immune proteins that attack the body’s own tissues
- The study of 3,548 Ontario residents shows the connection was strongest at higher pollution levels and higher antibody concentrations, suggesting a dose-response relationship
- Anti-nuclear antibodies often appear years before autoimmune diseases like lupus or rheumatoid arthritis become apparent, making them an early warning sign
- While the study cannot prove air pollution causes autoimmune disease, it strengthens evidence that even modest pollution levels within current legal limits may be affecting immune system function
Every breath of polluted air could be turning your immune system against you. Canadian researchers have discovered that tiny pollutants drifting through urban air may be altering how the immune system behaves over time, potentially raising the risk of autoimmune disease.
A study of 3,548 Ontario residents, published in Rheumatology, found that people breathing the most polluted air were up to 54% more likely to develop high levels of anti-nuclear antibodies, immune proteins that mistakenly attack the body’s own tissues. These antibodies often appear years before autoimmune diseases like lupus or rheumatoid arthritis become apparent, suggesting that long-term exposure to air pollution may be quietly flipping switches in the immune system long before anyone feels sick.
“PM2.5 exposure was associated with ANA positivity at high titres,” the research team wrote.
How Fine Particulate Matter Affects the Body
Fine particulate matter, known as PM2.5, consists of airborne particles smaller than 2.5 micrometers, roughly 30 times smaller than a human hair. Vehicle exhaust, industrial smokestacks, and burning fossil fuels pump these pollutants into the air we breathe.
Size matters here. Unlike larger particles that get trapped in the nose or throat, PM2.5 travels deep into the lungs and can slip into the bloodstream. Once inside, these particles set off a chain reaction of immune responses that scientists are only beginning to understand.
Researchers from McGill University and the University of Toronto analyzed blood samples collected between 2010 and 2013 from participants in the Ontario Health Study, a large research project tracking how environmental factors affect health. The study population was 62% female with an average age of 54.7 years.
Scientists calculated each person’s PM2.5 exposure based on their home postal code, using satellite images and air quality models to estimate average pollution levels over the five years before blood collection. Exposure ranged from 3.3 to 13.8 micrograms per cubic meter of air, with a median of 9.3. The World Health Organization recommends annual average PM2.5 levels stay below 5 micrograms per cubic meter.
Scientists tested the blood samples for anti-nuclear antibodies (ANA) using a laboratory technique that makes these antibodies glow under special lighting when they attach to cells. ANA levels are measured in concentrations called titres, where higher numbers mean stronger immune reactions. Readings of 1:160 or above are generally considered positive, but levels of 1:640 or 1:1280 are more worrying because they signal the immune system has kicked into overdrive.

Higher Pollution, Higher Antibody Levels
Comparing people living in the most polluted areas to those breathing the cleanest air revealed a striking pattern. Residents exposed to the highest pollution levels showed a 46% increased risk of testing positive for ANA at the 1:640 level and a 54% increased risk at the 1:1280 level.
The connection grew stronger as antibody levels climbed higher, suggesting pollution’s effects on the immune system intensify with both greater exposure and increased immune activation. At lower levels of 1:160 and 1:320, the risk appeared elevated but wasn’t statistically certain.
About 34% of participants tested positive for ANA at the 1:160 level, matching recent studies showing autoimmunity rates are climbing in developed countries. Females were twice as likely as males to have very high antibody levels (6.5% versus 3.2% at the 1:1280 level), reflecting the well-known pattern that autoimmune diseases affect women more often than men.
Researchers accounted for factors that could affect results, including age, sex, race and ethnicity, smoking history, income, and whether participants lived in cities or rural areas. The pollution-antibody connection held up after all these adjustments.
Why PM2.5 May Trigger Immune System Changes
When someone breathes in these pollutants, they settle deep in lung tissue and kick off inflammation. Immune cells rush to the area, treating the particles as foreign invaders and releasing chemical signals that create swelling and irritation.
Laboratory studies suggest that repeated exposure may contribute to ongoing inflammation that damages cells and tissues throughout the body. This constant assault is thought to eventually break down what scientists call “tolerance,” the immune system’s built-in ability to recognize the body’s own tissues as safe. Once that protection fails, antibodies that normally defend against bacteria and viruses start attacking the body instead.
Earlier epidemiological studies have connected PM2.5 exposure to higher rates of diseases where the immune system attacks multiple organs, including lupus, scleroderma, and rheumatoid arthritis. Laboratory experiments show that PM2.5 directly activates immune cells in lung tissue, but this study provides human evidence that exposure is associated with immune changes detectable in blood.
Lead author Naizhuo Zhao and senior author Sasha Bernatsky, both from the McGill University Health Centre’s Research Institute, noted that the results suggest effects are most visible at higher exposure levels. The immune system may tolerate low exposures but react more dramatically once pollution crosses a certain threshold.
Testing positive for ANA doesn’t mean someone will definitely develop an autoimmune disease. Many healthy people carry low-level ANA without ever experiencing symptoms. However, high ANA levels are considered an early warning sign, often showing up years before clinical disease appears.
The study captured a single moment in time rather than following people over years. Researchers couldn’t tell whether ANA developed during the five-year exposure period or earlier, or whether those antibodies will eventually cause disease. Future studies tracking people over time could reveal whether high ANA levels from pollution exposure actually lead to autoimmune disease diagnoses.
Researchers also couldn’t identify which specific parts of cells the antibodies were attacking. Some ANA patterns carry more serious health risks than others. With larger groups of people, future studies could explore whether PM2.5 triggers specific antibody types linked to particular diseases.
What This Means for Air Quality Policy
While Canadian air is generally cleaner than in many countries, the study shows that even relatively modest PM2.5 exposure within current legal limits may be affecting how the immune system works. If long-term PM2.5 exposure can push the immune system toward attacking itself, cutting air pollution could potentially prevent some cases of debilitating lifelong diseases.
For people already diagnosed with autoimmune conditions, the study raises questions about whether air quality should influence treatment decisions. People with family histories of autoimmunity might want to pay closer attention to air pollution exposure, though researchers stop short of making specific recommendations.
The study looked only at PM2.5, but people breathe other pollutants simultaneously, including nitrogen dioxide and ozone. Earlier analyses by the same research team found weaker connections between those pollutants and ANA, though more detailed studies examining multiple pollutants together could reveal combined effects.
Invisible particles floating through city air may be influencing immune behavior in subtle but meaningful ways. As air pollution continues affecting millions worldwide, understanding these immune system consequences becomes more urgent.
Paper Notes
Study Limitations
The research has several constraints affecting interpretation. Being cross-sectional, the study cannot establish whether PM2.5 exposure directly causes ANA development or merely correlates with it. Researchers cannot determine when antibody seroconversion occurred relative to the exposure window. The study lacked follow-up blood samples that would show whether ANA-positive individuals later developed clinical autoimmune diseases. Sample size prevented detailed analysis of specific ANA staining patterns, some of which carry higher clinical significance than others. The study did not assess exposure to other potential autoimmune triggers like occupational hazards (silica, solvents) or indoor air quality. Participants in the Ontario Health Study volunteered for health research and may not perfectly represent the general population. The use of postal codes to estimate exposure could introduce some measurement error, particularly in rural areas where postal codes cover larger geographic regions.
Funding and Disclosures
This work was supported by the Canadian Institutes of Health Research (grant 159682). The Ontario Health Study is funded by the Canadian Partnership Against Cancer, Health Canada, the Ontario Institute for Cancer Research, and the Government of Ontario. The study used data from ICES (formerly the Institute for Clinical Evaluative Sciences), which receives annual funding from the Ontario Ministry of Health and Long-Term Care. Several authors declared potential conflicts of interest: May Y. Choi receives consulting fees from Werfen, MitogenDx, AstraZeneca, GSK, Celltrion, and Organon, has received a grant from AstraZeneca, and serves as Associate Director of MitogenDx. Marvin J. Fritzler consults for Werfen and ThermoFisher Scientific and is Medical Director of Mitogen Diagnostics Corp. The remaining authors declared no conflicts of interest. The analyses, conclusions, and statements expressed are solely those of the authors and do not reflect positions of funding or data sources.
Publication Details
Authors: Naizhuo Zhao (Center for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec), Audrey Smargiassi (Center for Public Health Research, University of Montreal and CIUSSS du Centre-Sud-de-l’Île-de-Montréal, Montreal, Quebec), Hong Chen (Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario), May Y. Choi (Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta), Marvin J. Fritzler (Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta), Zahi Touma (Toronto Lupus Program, University of Toronto, Toronto, Ontario), J. Antonio Aviña-Zubieta (Arthritis Research Canada and Division of Rheumatology, University of British Columbia, Vancouver, British Columbia), Sasha Bernatsky (Center for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre and Division of Rheumatology, Department of Medicine, McGill University, Montreal, Quebec). Journal: Rheumatology, published online ahead of print October 22, 2025. DOI: 10.1093/rheumatology/keaf545. Study received June 1, 2025; accepted September 28, 2025. Published as an Open Access article under Creative Commons Attribution-NonCommercial License.







