Unraveling the immunopathology of infection-associated chronic illnesses: sex differences and predictive diagnostics 4058

Abstract Description Infection-associated chronic illnesses (IACI) represent a growing public health concern with limited diagnostic and therapeutic options. Our translational approach combines preclinical and clinical investigations to address this challenge. We have developed a murine model of long-term Borrelia burgdorferi infection which recapitulates key features of human IACI to identify early immune responses that predict long-term outcomes. Notably, we observe significant age and sex-dependent differences, with older females exhibiting the greatest morbidity across distinct genetic strains. We are developing predictive diagnostics to distinguish between protective and catastrophic immune responses, the latter characterized by atopic dermatitis, connective tissue breakdown, profound gynepathologies, compromised barrier integrity, and loss of tolerance to self-flora, with potential for neuroinflammation and mitochondrial dysfunction. In our clinical study, MAESTRO, we are employing a comprehensive approach to profile these catastrophic responses in individuals with IACI from Lyme or COVID by conducting neurological assessments, including eye movement tracking, cognitive function testing, and hypermobility assessments, incorporated with survey data and deep biological sample (including urine, sweat, saliva, blood, vaginal and rectal swabs) profiling for pathogen loads, dysbiosis, genomics, metabolomics and innovative immune trajectory mapping. Funding Sources R01 AI178713-01, MLSC, Emily and Malcolm Fairbairn donor advised fund Topic Categories Immune Mechanisms of Human Disease (HUM)