Serial cytokine profiling relative to CRS onset. Various cytokine values (log₁₀ transformed) are shown in relationship to CRS onset, which is indicated by time point = 0, stratified by carHLH status. Dots indicate the aggregated mean, and the error bands show the estimated 68% confidence interval. Cytokines with higher expression in patients with carHLH (as indicated in red) after CRS onset include, IFNγ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-13, MIP-1α, IL-4, IL-15, and IL-18. Cytokines with considerable overlap in values between those with and without carHLH (as indicated in blue) include TNFα, IL-2, GM-CSF, and IL-18, which shows parallel increase in level over time. The maximum number of patients is n = 21 for carHLH+ and n = 31 for carHLH− but may vary at each time point (supplemental Tables 2-3). For IL18bp, the cohort consisted of n = 14 for carHLH+ and n = 9 for carHLH−. A Wilcox rank sum test was used to identify differential cytokine levels between carHLH+ and carHLH− patients for each time point. Cytokine level were considered significant only if they remained significant at .05 (indicated with an asterisk) after FDR adjustment across the number of cytokines (n = 15) tested for each time point. For IL-18, the manufacturer’s kit documentation lists reference range (healthy controls; n = 35) for normal human plasma to be 1778 pg/mL – 6428 pg/mL.