C32-30 Cytokine Profiles in Sickle Cell Disease Patients With and Without Prior History of Acute Chest Syndrome

Rationale

Pulmonary complications are prevalent in sickle cell disease (SCD), with acute chest syndrome (ACS) being a frequent and severe manifestation. Despite being a chronic inflammatory disease, data on the relationship between inflammatory mediators and SCD-related pulmonary complications are limited. Therefore, we sought to evaluate the relationship between plasma cytokine/chemokine profiles and the history of ACS in individuals with SCD. We hypothesized that individuals with SCD who have a history of ACS exhibit higher baseline levels of inflammatory mediators compared to those without a history of ACS.

Methods

We conducted a retrospective case-control study of individuals with SCD aged 5-22 years. Cases had documented history of ACS (yes/no); controls had no history of ACS. ACS episode(s) could have occurred at any time before or after plasma sample collection. Plasma samples were obtained during steady state, defined as absence of acute illness within the preceding 2 weeks and analyzed in duplicate using a 96-multiplex cytokine/chemokine assay. Descriptive statistics summarized demographic and clinical characteristics. Cytokine/chemokine levels were compared between cases and controls using Wilcoxon testing, with false discovery rate (FDR) adjustment applied for multiple comparison.

Results

A total of 74 individuals with SCD were included, with a mean age of 13.3 years (SD 4.9), and 55.4% (n = 41) were male. The majority had hemoglobin SS disease (71.6%, n = 53). There were 69% (n = 51) who had had history of ACS and 31% (n = 23) did not. Of the 96 cytokine/chemokine levels assessed, there were 8 that showed nominal differences between cases and controls on initial analyses with lower levels of IL-1β, IL-2, IL-15, IL-17A, GM-CSF, TNF-β, and MCP-1 observed in the ACS group compared to the non-ACS group and higher levels of MPIF-1 (CCL23) in the ACS group (all p < 0.05). However, after adjusting for FDR, no cytokine/chemokine differences reached statistical significance, highlighting the exploratory nature of this analysis. Figure 1 shows the overall cytokine/chemokine expression patterns between the two groups.

Conclusion

Contrary to expectations, a history of ACS is potentially associated with altered baseline immune signaling characterized primarily by lower steady state cytokine/chemokine levels. These data suggest potential immune modulation, reprogramming, and/or exhaustion rather than persistent hyperinflammation or absence of inflammation. While these findings did not withstand multiplecomparison correction, they highlight biologically plausible immune phenotypes that may contribute to pulmonary risk heterogeneity in SCD. Larger, longitudinal studies are needed to determine whether steady state cytokine/chemokine profiles can inform risk stratification or mechanistic pathways underlying ACS.

This abstract is funded by: National Institute of Neurological Disorders and Stroke (NINDS)