Figure 2.
Longitudinal differences in protein expression and NETosis-related assays. Results from the longitudinal linear mixed model analysis (with prediction intervals calculated based on standard error), followed by protein expression assays. (A) CD33 expression after CAR T-cell infusion in participants (n = 22) leading up to CRS onset or leading up to day 7 to 9 in those without CRS. NPX represents normalized protein eXpression on a log2 scale (Olink Proteomics). (B) Table of proteins with a significant CRS term within the linear mixed model, indicating constitutively higher or lower expression levels over time leading to CRS onset. Light blue shading indicates proteins that were also found to be differentially abundant at peak CRS in Figure 1D. (C) MPO expression after CAR T-cell infusion in participants (n = 22) leading up to CRS onset or leading up to day 7 to 9 in those without CRS. NPX represents normalized protein eXpression on a log2 scale (Olink Proteomics). (D) Table of proteins with significant changes over time only in participants who developed CRS, as indicated by the interaction term CRS:time P-value and significance ratio (ratio of interaction term P-value/CRS term P-value). (E) Pre-CAR T–cell infusion CitH3 and (F) Calprotectin levels, measured using enzyme-linked immunosorbent assay, in participants (n = 86) who later developed various grades of CRS. For CitH3 levels from 8 patients, a linear regression–based rescaling was done to correct for a batch effect (see supplemental Methods for more detail).

Longitudinal differences in protein expression and NETosis-related assays. Results from the longitudinal linear mixed model analysis (with prediction intervals calculated based on standard error), followed by protein expression assays. (A) CD33 expression after CAR T-cell infusion in participants (n = 22) leading up to CRS onset or leading up to day 7 to 9 in those without CRS. NPX represents normalized protein eXpression on a log2 scale (Olink Proteomics). (B) Table of proteins with a significant CRS term within the linear mixed model, indicating constitutively higher or lower expression levels over time leading to CRS onset. Light blue shading indicates proteins that were also found to be differentially abundant at peak CRS in Figure 1D. (C) MPO expression after CAR T-cell infusion in participants (n = 22) leading up to CRS onset or leading up to day 7 to 9 in those without CRS. NPX represents normalized protein eXpression on a log2 scale (Olink Proteomics). (D) Table of proteins with significant changes over time only in participants who developed CRS, as indicated by the interaction term CRS:time P-value and significance ratio (ratio of interaction term P-value/CRS term P-value). (E) Pre-CAR T–cell infusion CitH3 and (F) Calprotectin levels, measured using enzyme-linked immunosorbent assay, in participants (n = 86) who later developed various grades of CRS. For CitH3 levels from 8 patients, a linear regression–based rescaling was done to correct for a batch effect (see supplemental Methods for more detail).

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