Background: Rheumatoid factor (RF) is a classical autoantibody reflecting B-cell dysregulation and autoimmunity. Sulfur mustard (SM) is a potent chemical warfare agent that induces chronic pulmonary, dermatological, and ocular injuries, often accompanied by persistent inflammation, oxidative stress, and immune perturbation. This study aimed to investigate RF levels in SM-exposed individuals compared to unexposed controls, and to explore differences based on sex and clinical manifestations.
Materials and Methods: A total of 139 SM-exposed veterans and 109 unexposed controls were enrolled. Serum RF concentration was measured using ELISA. Participants were stratified by sex and by severity of lung, skin, and eye involvement.
Results: RF levels were significantly lower in the exposed group compared to controls (P<0.01). Sex-stratified analysis revealed a pronounced reduction in RF levels in exposed females compared to control females (P<0.01), whereas RF levels in males did not differ significantly. Analysis of clinical manifestations demonstrated consistently lower RF levels in exposed individuals across lung, skin, and eye involvement, with significant differences in most comparisons versus controls. Notably, RF reduction did not correlate with disease severity, suggesting that exposure, rather than disease severity, drives this effect.
Conclusion: Long-term SM exposure is associated with reduced RF levels, particularly in women, and with differences in clinical manifestations. These findings suggest chronic immune remodeling or B-cell dysfunction rather than classical autoantibody-driven autoimmunity. The observed heterogeneity compared with previous studies underscores the need for longitudinal and mechanistic investigations, including B-cell phenotyping, cytokine and oxidative stress profiling, and sex-specific analyses, better to understand the long-term immunologic consequences of SM exposure.