Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Oct 24;7(20):6134-6139.
doi: 10.1182/bloodadvances.2023010708.

Free interleukin-18 is elevated in CD22 CAR T-cell-associated hemophagocytic lymphohistiocytosis-like toxicities

Joseph M Rocco  1 , Jon Inglefield  2 , Bonnie Yates  3 , Daniel A Lichtenstein  4   5 , Yanyu Wang  2 , Laurence Goffin  6 , Djordje Filipovic  6 , Eduardo J Schiffrin  6 , Nirali N Shah  3
Affiliations

Free interleukin-18 is elevated in CD22 CAR T-cell-associated hemophagocytic lymphohistiocytosis-like toxicities

Joseph M Rocco et al. Blood Adv. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: D.F., L.G., and E.J.S. are employees of AB2 Bio Ltd. The remaining authors declare no competing financial interests. L.G. has since left AB2 Bio before submission and is currently affiliated.

The current affiliation for L.G. is Neuroimmunology and Neuroinflammation, Lundbeck, Valby, Denmark.

Figures

Figure 1.
Figure 1.
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.
Figure 2.
Figure 2.
Correlation matrix and heatmap with unsupervised clustering comparing the relationship of IL-18 axis biomarkers and other cytokines during CRS and carHLH. Multiparameter Spearman correlation matrix, comparing the average biomarkers levels per patient from their inflammatory course (A). Heatmap with unsupervised clustering analysis demonstrates the patients with carHLH cluster separately from those with CRS only but form 2 distinct clusters (B). Biomarker levels represent averages from inflammatory course beginning at CRS onset and ending at the timepoint before the response to anti-inflammatory therapy, as defined based on the downtrending levels of total IL-18, IL-18BP, and free IL-18. Analysis was performed in R using the FactoMineR, factoextra, and pheatmap packages. Matrix in panel A was created in R using corrplot package, and significant associations are denoted by ∗P < .05; ∗∗P < .01; ∗∗∗P < .001.
See this image and copyright information in PMC

References

    1. Diorio C, Shraim R, Myers R, et al. Comprehensive serum proteome profiling of cytokine release syndrome and immune effector cell associated neurotoxicity syndrome in B-cell ALL patients receiving CART19. Clin Cancer Res. 2022;28(17):3804–3813. - PMC - PubMed
    1. Hines MR, Knight TE, McNerney KO, et al. Immune effector cell associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) Transplant Cell Ther. 2023;29(7):438.e1–438.e16. - PMC - PubMed
    1. Lin H, Scull BP, Goldberg BR, et al. IFN-gamma signature in the plasma proteome distinguishes pediatric hemophagocytic lymphohistiocytosis from sepsis and SIRS. Blood Adv. 2021;5(17):3457–3467. - PMC - PubMed
    1. Bracaglia C, de Graaf K, Pires Marafon D, et al. Elevated circulating levels of interferon-gamma and interferon-gamma-induced chemokines characterise patients with macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Ann Rheum Dis. 2017;76(1):166–172. - PubMed
    1. Crayne CB, Albeituni S, Nichols KE, Cron RQ. The immunology of macrophage activation syndrome. Front Immunol. 2019;10:119. - PMC - PubMed

Publication types

MeSH terms

Substances