Circulating plasma IL-13 and periostin are dysregulated type 2 inflammatory biomarkers in prurigo nodularis: A cluster analysis
Varsha Parthasarathy, Karen Cravero, Junwen Deng, Zhe Sun, Sarah Engle, Autum N. Auxier, Nathan Hahn, Jonathan T. Sims, Angela J. Okragly, Martin P. Alphonse, Shawn G. Kwatra
Abstract
Importance Prurigo nodularis (PN) is a chronic heterogeneous inflammatory skin disease. Objective To elucidate which components of type 2 inflammation are dysregulated systemically in PN. Design Whole blood was obtained from PN patients with uncontrolled disease and control patients without pruritus. Plasma was assayed for IL-4, IL-5, IL-13, IgE, and periostin. ANOVA was utilized to compare PN and control patients and multiple-hypothesis adjusted p- value was calculated with the significance threshold at 0.05. Clustering was performed using K-means clustering. Participants PN patients ( n = 29) and controls ( n = 18) from Johns Hopkins Dermatology had similar age sex, and race distributions. Results Single-plex assays of the biomarkers demonstrated elevated circulating plasma IL-13 (0.13 vs. 0.006 pg/mL, p = 0.0008) and periostin (80.3 vs. 60.2 ng/mL, p = 0.012) in PN compared to controls. IL-4 (0.11 vs. 0.02 pg/mL, p = 0.30) and IL-5 (0.75 vs. 0.40 pg/mL, p = 0.10) were not significantly elevated, while IgE approached significance (1202.0 vs. 432.7 ng/mL, p = 0.08). Clustering of PN and control patients together revealed two clusters. Cluster 1 ( n = 36) consisted of 18 PN patients and 18 controls. Cluster 2 ( n = 11) consisted entirely of PN patients ( p < 0.01). Cluster 2 had higher levels of IL-13 (0.33 vs. 0.008 pg/mL, p = 0.0001) and IL-5 (1.22 vs. 0.43 pg/mL, p = 0.03) compared to cluster 1. Conclusion and relevance This study demonstrates elevation of IL-13 and periostin in the blood of PN patients, with distinct clusters with varying degrees of type 2 inflammation. Given this heterogeneity, future precision medicine approaches should be explored in the management of PN.