Sickle cell disease (SCD) is a single-gene illness characterized by chronic inflammation, decreased quality of life, and early mortality; however, outcomes are highly variable between individuals, suggesting a substantial role of social and environmental factors in disease outcomes. Data suggest that individuals living with SCD have greater eosinophil counts and activation, and higher prevalence of asthma and wheezing than those without SCD, suggesting a role for eosinophilic inflammation in SCD. In other diseases, eosinophilic inflammation has been linked to social and environmental factors, particularly in minoritized populations. To date, however, few human studies have explored the pathophysiology of social and environmental exposures in SCD. This study tested whether eosinophilic inflammation was related to location-based measures of social disadvantage or public housing in 79 individuals with SCD, without diagnoses of asthma, who were prospectively followed over one year. Home addresses were geocoded and matched to principal-components derived, validated measures of local neighborhood social disadvantage and to locations of public housing facilities. Serum peripheral eosinophils, IL-13 and IL-5 were measured every 8 weeks. In fully-adjusted models, statistically significant, linear relationships were observed between the degree of social disadvantage and level of eosinophilic inflammation; however, the direction of that relationship was opposite for patients who live in public housing and those who do not. For those living in public housing, greater social disadvantage was associated with increased eosinophilic inflammation. For those in private housing, greater social disadvantage was associated with progressively less eosinophilic inflammation. These strong, and somewhat unexpected, relationships demonstrate that subtle differences in social exposures and home environment have differential effects on inflammatory profiles which may have larger implications for disease and health, especially in chronic diseases such as SCD. To understand the mechanisms of these effects may require highly granular studies that catalog the many factors underlying the social environment and inflammation.

JAG reports funding from Genentech for Contracted clinical research, and DSMB participation for Novo Nordisk.

SM, RJW, and MM acknowledge support from 5K12ES033594. RJW acknowledges support from 5UG3OD023337, 5UL1TR004419, 5P30ES023515, 5R01ES033436, 1R21ES035169. JAG acknowledges support from 5U01HL167036, 5R01HL159116, 5R01HL142671.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB of Icahn School of Medicine at Mount Sinai gave ethical approval for this work.

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