Background <p>The interaction between fine particulate matter (PM2.5) and genetic factors is thought to play a significant role in the development of autoimmune diseases. However, the impact of PM2.5 exposure on the onset of these diseases remains unclear. This population-based cohort study investigated the effect of year-to-year variations in PM2.5 exposure levels on incident autoimmune disease risk in Taiwanese adults.</p> Methods <p>In this longitudinal study, we followed-up 276,254 adults from the Taiwan MJ cohort (2005–2017) for 9.3 years to identify incident autoimmune diseases cases, ascertained from the patients’ clinical and laboratory reports. Autoimmune diseases were categorized as systemic and organ-specific. Data on residential address-specific annual PM2.5 concentrations were obtained from Taiwan Air Quality-Monitoring sites. A time-dependent Cox regression model, considering death as a competing risk, was used to assess the effect of year-to-year variations in PM2.5 exposure levels on autoimmune disease risk.</p> Results <p>During the 2,579,362 person-years of follow-up, new-onset autoimmune diseases were observed in 958 (0.35%) individuals, corresponding to an incident density of 37.14 per 100,000 person-years. Participants with high PM2.5 exposure levels (per 5-µg/m³ increase) had a significantly increased risk of incident autoimmune diseases (adjusted hazard ratio [aHR], 2.97; 95% confidence interval [CI], 2.84–3.11), particularly systemic lupus erythematosus (SLE) (aHR, 3.28; 95% CI, 2.99–3.59) and Sjögren’s syndrome (aHR, 2.82; 95% CI, 2.66–2.98).</p> Conclusions <p>Proactive air pollution control strategies are crucial for the prevention of autoimmune diseases, particularly SLE and Sjögren’s syndrome.</p>