Circulating Brain-Reactive Autoantibody Profiles in Military Breachers Exposed to Repetitive Occupational Blast.

Military breachers are routinely exposed to repetitive low-level blast overpressure, placing them at elevated risk for long-term neurological sequelae. Mounting evidence suggests that circulating brain-reactive autoantibodies, generated following CNS injury, may serve as both biomarkers of cumulative damage and drivers of secondary neuroinflammation. In this study, we compared circulating autoantibody profiles in military breachers ( = 18) with extensive blast exposure against unexposed military controls ( = 19). Using high-sensitivity immunoassays, we quantified IgG and IgM autoantibodies targeting glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and pituitary (PIT) antigens. Breachers exhibited significantly elevated levels of anti-GFAP IgG ( < 0.001) and anti-PIT IgG ( < 0.001) compared to controls, while anti-MBP autoantibody levels remained unchanged. No significant differences were observed for any IgM autoantibody measurements. These patterns suggest that repetitive blast exposure induces a chronic, adaptive immune response rather than a short-lived acute phase. The elevated IgG autoantibodies highlight the vulnerability of astrocytes, myelin, and the hypothalamic-pituitary axis to ongoing immune-mediated injury following repeated blast insults, likely reflecting sustained blood-brain barrier disruption and neuroinflammatory processes. Our findings underscore the potential of CNS-targeted IgG autoantibodies as biomarkers of cumulative brain injury and immune dysregulation in blast-exposed populations. Further research is warranted to validate these markers in larger, more diverse cohorts, and to explore their utility in guiding interventions aimed at mitigating neuroinflammation, neuroendocrine dysfunction, and long-term neurodegenerative risks in military personnel and similarly exposed groups.