{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:03:50Z","timestamp":1791821030393,"version":"4.3.4"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013173","name":"Gyeonggi-do Regional Research Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013173","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic spontaneous urticaria (CSU) exhibits marked immunologic heterogeneity, and a substantial proportion of patients show delayed or absent responses to anti-IgE therapy. While cytokines are implicated in CSU pathophysiology, their integrated network architecture in relation to treatment response remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed serum cytokine profiles in 65 antihistamine-refractory CSU patients who received omalizumab for \u2265 6 months. Fifteen cytokines were quantified at baseline and month 6 using a multiplex bead-based assay. Treatment responses were categorized as early and well-controlled (EW), late or partly controlled (LP), or no-response (NR) based on UAS7 and UCT criteria. Cytokine compositional balance, network topology, multinomial regression, and structural equation modeling were applied to delineate immune endotypes associated with treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 65 patients, 33 (50.8%) were EW, 16 (24.6%) were LP, and 16 (24.6%) were NR. Among baseline cytokines, interleukin (IL)-13 was the only analyte differing significantly in absolute concentration, being higher in LP and NR than in EW patients. Compositional analyses revealed an IL-13-dominant imbalance strongly enriched in LP and NR. Cytokine-network analysis demonstrated cohesive interactions in EW, partial disruption in LP, and fragmented innate-Th17\/Th1 connectivity in NR. Multinomial regression and structural path analyses identified IL-13 as a central node linking multiple inflammatory pathways associated with inadequate response. Longitudinally, meaningful cytokine modulation was observed only in EW, whereas LP and NR exhibited minimal or no changes despite treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Baseline cytokine imbalances and network architecture are closely associated with heterogeneity in omalizumab response. An IL-13\u2013dominant, biologically rigid cytokine profile, together with persistent innate-Th17 activity in certain patients, may define CSU endotypes less amenable to anti-IgE therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1783483","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T04:14:37Z","timestamp":1776658477000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cytokine imbalance and immune network endotypes underlying heterogeneous response to omalizumab in chronic spontaneous urticaria"],"prefix":"10.3389","volume":"17","author":[{"given":"Young-Min","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Ajou University School of Medicine","place":["Suwon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Trials Center, Ajou University Medical Center","place":["Suwon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hyuk","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Ajou University School of Medicine","place":["Suwon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da-Hye","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Ajou University School of Medicine","place":["Suwon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Woo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Ajou University School of Medicine","place":["Suwon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Ajou University School of Medicine","place":["Suwon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2020.12.5.750","article-title":"The KAAACI\/KDA evidence-based practice guidelines for chronic spontaneous urticaria in korean adults and children: part 2. 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