Novel Insights Into the Effects of Interleukin 6 Antagonism in Non–ST‐Segment–Elevation Myocardial Infarction Employing the SOMAscan Proteomics Platform

Figures

• 

  Figure 1. Difference in relative abundance of the 1074 SOMAscan proteins between the placebo and tocilizumab groups. Shown on the x axis is the log‐relative fluorescence unit (RFU) difference between groups, and on the y axis is the −log P value. Named proteins (in green) are those surpassing the false discovery rate (FDR) of 0.1 (Benjamini‐Hochberg). The Bonferroni threshold is also shown. The slow off‐rate aptamer name is used. Soluble interleukin 6 (IL‐6) receptor is beyond the axis used (P=2.3×10−20). C5A indicates complement component 5a anaphylatoxin; IGFBP4, insulin‐like growth factor‐binding protein 4; LBP, lipopolysaccharide‐binding protein; PRTN3, proteinase 3; SerpinA3, serpin family A member 3; and VEGFA, vascular endothelial growth factor A.

• 

  Figure 2. Plasma concentrations of proteins discovered by SOMAscan measured by enzyme immunoassay in the whole study cohort over time. Plasma levels of LBP (lipopolysaccharide‐binding protein), CCL23 (C‐C motif ligand 23) (cross‐reacts with Ck‐beta‐8‐1), HAMP (hepcidin antimicrobial peptide), IGFBP4 (insulin‐like growth factor‐binding 4), PRTN3 (proteinase 3), SerpinA3 (serpin family A member 3), VEGF (vascular endothelial growth factor A), and C5A (complement component 5a anaphylatoxin) during hospitalization (baseline to 3 days) and follow‐up (3 and 6 months) in patients with non–ST‐segment–elevation myocardial infarction receiving placebo (n=59) or tocilizumab (n=58) and analyzed according to whether the patient did (n=88) or did not (n=29) undergo percutaneous coronary intervention (PCI) (n=88). Circles and bars represent estimated marginal means and 95% CIs normalized for baseline values. The P value represents the effect of treatment.

• 

  Figure 3. Associations between newly identified proteins modulated by tocilizumab and parameters measured in the original study. Dotplots showing associations between area under the curve (log‐transformed) of plasma levels of LBP (lipopolysaccharide‐binding protein), CCL23 (C‐C motif ligand 23), hepcidin, IGFBP4 (insulin‐like growth factor‐binding 4), and PRTN3 (proteinase 3) with CRP (C‐reactive protein), hsTnT (high‐sensitivity troponin T), NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), interleukin 6 (IL‐6), and neutrophil counts during hospitalization (baseline to 3 days) in patients with non–ST‐segment–elevation myocardial infarction receiving placebo (red circles, n=59) or tocilizumab (blue circles n=58). Black lines represent the regression line and the numbers in the bottom right the correlation coefficient for the whole group. If an interaction with tocilizumab was detected (green frames, see Statistical Analysis), the regression lines and numbers reflect either placebo (red) or tocilizumab (blue).