Individual and cumulative trends in IL-18 axis biomarkers across all time points and normalized to the onset of CRS and inflammatory complications. (A) Individual trends in total IL-18 (blue line) and free IL-18 (red line) in patients with carHLH. (B) Longitudinal trend of IL-18, IL-18BP, and free IL-18 at all time points tested for control patients with CRS only (blue) compared with that for patients with carHLH (red). Biomarker levels at each time point are represented by median with standard error bars. (C) IL-18 associated biomarkers were then normalized to onset of CRS and plotted from time points before CRS and during the inflammatory episodes (CRS ± carHLH). Dots correspond to individual patient values and slopes with standard error represent regression lines of the trends of each group over time. Linear mixed regression models were used to compare the longitudinal changes per time point between the 2 groups. P values represent the mixed regression model, comparing the interaction of the biomarker change per time point between the groups.