Predictive markers of the exaggerated response to NM enrich IL-17 signaling.
inflammation
INFLAMMATION
Mild and Severe NM response types were initially identified from data obtained during the intervention phase of this study (participants’ second NM exposure). However, because this divergence was determined to be intervention independent, we hypothesized that a participant’s fated response type was determined prior to the second NM exposure. Thus, we conducted a “look-back” analysis to determine if Mild and Severe responders could be identified in the control phase of this study (participants’ first NM exposure). Identification of early markers for a severe response fate may have utility in predicting the clinical response to NM. By labeling 72hrs P-E samples in the PCA according to their 72hrs P-I Mild or Severe designations (Differential expression analysis with RNA-Seq data demonstrated 42 significantly upregulated and 23 downregulated (logIn agreement with the DEG and DEP findings, 72hrs P-E Severe demonstrated higher clinical measures of inflammation than 72hrs P-E Mild. Higher severity scores for inflammation (These results suggest that IL-17 signaling may be involved in priming the body to mount a severe response to subsequent NM exposures. The 72hrs P-E Severe participants expressed early inflammatory biomarkers involved in IL-17 signaling, such as CXCL8 and CCL20, which may have utility as a diagnostic panel for predicting adverse clinical reactions.