SMILE: Sickle Cell Disease Microbiologic and Immunologic Links to Health Equity

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PROJECT SUMMARY The objective of this proposal is to understand how immune responses in children with sickle cell disease (cwSCD) are shaped by exposures in their local environment and lead to disparate health outcomes. The rationale underlying this proposal is that our prior work demonstrates that cwSCD have unique alterations in their blood inflammatory transcriptional profiles and upper airway microbiomes at baseline with further perturbations during acute complications. We have also shown that the public health exposome (PHE), which includes stressors from the natural, built, social, and policy environments, influences inflammation in chronic diseases. The proposed research is significant because SCD disproportionally impacts underrepresented minority populations with many children frequently exposed to and challenged by multiple negative social determinates of health. The central hypothesis is that the PHE is associated with altered inflammatory signaling in cwSCD leading to increased frequency of acute complications. The central hypothesis will be tested by pursuing two specific aims: 1) Characterize SCD baseline immune signatures and 2) Link environmental and socio- demographic factors from the PHE 4.0 database to SCD outcomes at the individual, community, and population-levels. We will pursue these aims using sophisticated transcriptional and proteomic profiling of immune signatures combined with a novel database of real-time PHE data and well-characterized clinical data. Our interdisciplinary team of experts in immunology, microbiology, and public health along with hematology, pulmonology, and ID specialists combines complementary clinical and research expertise to take a new approach to study outcomes in cwSCD. The expected outcome of this work will establish a unique profile of immune signatures integrated with the PHE to generate an unparalleled dataset of biologic data with societal and environmental factors that influence health in cwSCD. The long-term goal is to integrate findings with a comprehensive assessment of the airway and gut microbiomes and hormonal stress responses from this cohort and longitudinally evaluate how immune-environmental factors predict acute complications. Ultimately, we will create comprehensive phenotypic profiles of cwSCD to help improve prediction, prevention, and treatment of acute complications in cwSCD that move beyond the current paradigm of supportive and/or reactive care.