{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:09:47Z","timestamp":1787065787770,"version":"build-2736575974"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T00:00:00Z","timestamp":1670284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Prurigo nodularis (PN) is a chronic heterogeneous inflammatory skin disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To elucidate which components of type 2 inflammation are dysregulated systemically in PN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>p-<\/jats:italic>\n                      value was calculated with the significance threshold at 0.05. Clustering was performed using K-means clustering.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>\n                      PN patients (\n                      <jats:italic>n<\/jats:italic>\n                      = 29) and controls (\n                      <jats:italic>n<\/jats:italic>\n                      = 18) from Johns Hopkins Dermatology had similar age sex, and race distributions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Single-plex assays of the biomarkers demonstrated elevated circulating plasma IL-13 (0.13 vs. 0.006 pg\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0008) and periostin (80.3 vs. 60.2 ng\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.012) in PN compared to controls. IL-4 (0.11 vs. 0.02 pg\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.30) and IL-5 (0.75 vs. 0.40 pg\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.10) were not significantly elevated, while IgE approached significance (1202.0 vs. 432.7 ng\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.08). Clustering of PN and control patients together revealed two clusters. Cluster 1 (\n                      <jats:italic>n<\/jats:italic>\n                      = 36) consisted of 18 PN patients and 18 controls. Cluster 2 (\n                      <jats:italic>n<\/jats:italic>\n                      = 11) consisted entirely of PN patients (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01). Cluster 2 had higher levels of IL-13 (0.33 vs. 0.008 pg\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0001) and IL-5 (1.22 vs. 0.43 pg\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.03) compared to cluster 1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and relevance<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2022.1011142","type":"journal-article","created":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T01:40:22Z","timestamp":1670290822000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Circulating plasma IL-13 and periostin are dysregulated type 2 inflammatory biomarkers in prurigo nodularis: A cluster 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