{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T15:22:16Z","timestamp":1772551336808,"version":"3.50.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Stressful physical or psychological events can trigger acute swelling attacks in patients with Hereditary Angioedema due to C1 Inhibitor deficiency (HAE-C1INH), although the stress\u2013disease relationship remains unclear. The Socially Evaluated Cold Pressor Test (SECPT) reliably induces acute stress under controlled conditions. This study aimed to compare perceived stress, inflammatory markers, and cardiovascular responses to SECPT between HAE-C1INH patients and healthy controls (HC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty HAE-C1INH patients (9 males, 44 \u00b1 14 years) and age and sex matched HC underwent a 3-minute SECPT. Participants completed questionnaires assessing anxiety and depression (HADS), pain catastrophizing (PCS), and subjective stress (0\u2013100 scale) before and after SECPT. Heart rate (HR) and arterial pressure (AP) were recorded. Blood samples for inflammatory cytokines (IL-6, IL-1\u00df, TNF-\u03b1) were collected at baseline, and 10 and 40 minutes after SECPT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared to HC, patients showed higher baseline HADS-A (7.3 \u00b1 4.5 vs 4.7 \u00b1 2.7), overall PCS (19.7 \u00b1 12.6 vs 12.9 \u00b1 8.7), and perceived stress during SECPT (60.6 \u00b1 34.3 vs 34.6 \u00b1 23.8). IL-6 levels were higher at baseline and 10 minutes post-test (2.63 \u00b1 1.21 vs 1.84 \u00b1 0.87; 2.78 \u00b1 1.20 vs 1.91 \u00b1 0.79 pg\/ml), as were TNF-\u03b1 levels across all phases (4.19 \u00b1 1.38 vs 3.26 \u00b1 1.55; 4.09 \u00b1 1.39 vs 3.40 \u00b1 1.48; 4.09 \u00b1 1.28 vs 3.20 \u00b1 1.57) while IL-1 \u00df remained unchanged. HR and AP variations were similar between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>HAE-C1INH patients exhibited heightened perceived stress response to SECPT, and elevated baseline inflammation, despite comparable cardiovascular reactivity. These findings highlight a complex psychophysiological\u2013inflammatory interplay in acute stress responses, suggesting the need to integrate psychological and biological frameworks in understanding HAE-C1INH triggers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trials code<\/jats:title>\n                    <jats:p>NCT06414252.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1736589","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:56:48Z","timestamp":1767769008000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Functional physiological, psychological, and biochemical reactivity to socially evaluated cold pressor test in hereditary angioedema patients (FRoSEn)"],"prefix":"10.3389","volume":"16","author":[{"given":"Beatrice","family":"De 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