Systemic longitudinal immune profiling to noninvasively predict fracture nonunion 3874

Abstract Description Traumatic tibia fractures are prone to nonunion, a debilitating and painful condition of incomplete bone healing. Worse, nonunion is typically diagnosed 9 months after injury, prolonging patient suffering and limiting the potential of regenerative treatments. While preclinical studies implicate a dysregulated immune response as a possible early predictor and underlying cause of nonunion, more clinical studies are needed. To address this need, we enrolled patients with open tibia fractures in a clinical study with the goal of predicting nonunion based on circulating immune biomarkers. Peripheral blood was collected longitudinally, (1) intra-operatively, (2) at point-of-discharge, (3) 2-4 weeks post-surgery, and (4) 6-8 weeks post-surgery. The cellular fraction was analyzed via spectral flow cytometry for 16 innate and adaptive immune cells, while plasma was stored for future comprehensive proteomic analysis (1500 analytes). Preliminary results revealed, on average, suppressed T- and B-lymphocytes and elevated myeloid cells immediately after injury, resolving by 6-8 weeks. We also observed high inter-patient variation (CV > 100%) in levels of regulatory T-cells, myeloid-derived suppressor cells, and nonclassical monocytes, all populations that have previously been correlated with nonunion. We will continue to enroll and follow patients until diagnosis of healed vs. nonunion and build AI-powered predictive models based on integrated cell and proteome profiles. Funding Sources Supported by the Department of Defense Congressionally Directed Medical Research Program (CDMRP). Topic Categories Immune Mechanisms of Human Disease (HUM)