Abstract
Obesity is a growing global health concern and a chronic inflammatory state that may influence immune tolerance and autoimmunity. While previous studies have examined links between obesity and selected immune-mediated inflammatory diseases (IMIDs), the broader impact of obesity across a wide spectrum of IMIDs remains unclear. We conducted a large-scale cohort study using the TriNetX global electronic health record database. Adults aged ≥ 18 years with a body mass index (BMI) ≥ 18.5 kg/m(2) recorded between 2015 and 2019 were included. Participants were classified as obese (BMI ≥ 30) or non-obese (BMI 18.5-29.9), with a confirmatory BMI recorded within 60 days. Individuals with pregnancy-related diagnoses or pre-existing IMIDs were excluded. Fifteen IMIDs were assessed as primary outcomes. Propensity score matching was performed, and Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses, dose-response analyses, and control outcomes were used to evaluate robustness and specificity. A total of 698,624 matched pairs were analyzed. Obesity was significantly associated with increased risks of several IMIDs, particularly psoriatic arthritis (HR 1.74, 95% CI 1.59-1.89), type 1 diabetes mellitus (HR 1.41, 95% CI 1.36-1.47), and rheumatoid arthritis (HR 1.20, 95% CI 1.16-1.25). Inverse associations were observed for Sjögren's syndrome (HR 0.86, 95% CI 0.81-0.90) and systemic sclerosis (HR 0.75, 95% CI 0.65-0.87). Findings were robust across multiple sensitivity analyses. A dose-response gradient was observed for several IMIDs, with significant linear trends for rheumatoid arthritis and psoriasis (P for trend < 0.05). Obesity is associated with increased risks for several, but not all, IMIDs, with dose-response patterns in select conditions. These findings highlight the immunological impact of excess adiposity and support further research to evaluate obesity as a potentially modifiable risk factor for certain autoimmune diseases.