{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T20:04:16Z","timestamp":1788206656876,"version":"build-2803163510"},"reference-count":37,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"46","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,11,17]]},"abstract":"<jats:p>Vascular dysfunction resulting from endothelial hyperpermeability is a common and important feature of critical illness due to sepsis, trauma, and other conditions associated with acute systemic inflammation. Clarkson disease [monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome (ISCLS)] is a rare, orphan disorder marked by spontaneous and recurrent episodes of hypotensive shock and peripheral edema due to widespread vascular leakage in peripheral tissues. Mortality from acute flares approaches 30% due to lack of effective therapies. We evaluated a monoclonal antibody (4E2) specific for the endothelial receptor tyrosine kinase Tie2 in ISCLS models. 4E2 activated Tie2 in ISCLS patient-derived endothelial cells and reduced baseline and proinflammatory mediator-induced barrier dysfunction. 4E2 also reduced mortality and\/or vascular leakage associated with systemic histamine challenge or influenza infection in the SJL\/J mouse model of ISCLS. These findings support a critical role for Tie2 dysregulation in ISCLS and highlight a viable therapeutic approach to this catastrophic disorder.<\/jats:p>","DOI":"10.1126\/sciadv.adi1394","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T19:01:01Z","timestamp":1700247661000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":12,"title":["A ligand-independent Tie2-activating antibody reduces vascular leakage in models of Clarkson disease"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8692-4572","authenticated-orcid":true,"given":"Ararat J.","family":"Ablooglu","sequence":"first","affiliation":[{"name":"Lung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Desai","sequence":"additional","affiliation":[{"name":"Lung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2695-9685","authenticated-orcid":true,"given":"Jin-San","family":"Yoo","sequence":"additional","affiliation":[{"name":"R&amp;D Center, PharmAbcine Inc., 70, Yuseong-daero 1689 beon-gil, Yuseong-gu, Daejeon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheon Ho","family":"Park","sequence":"additional","affiliation":[{"name":"R&amp;D Center, PharmAbcine Inc., 70, Yuseong-daero 1689 beon-gil, Yuseong-gu, Daejeon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7739-5977","authenticated-orcid":true,"given":"Eun-Ah","family":"Lee","sequence":"additional","affiliation":[{"name":"R&amp;D Center, PharmAbcine Inc., 70, Yuseong-daero 1689 beon-gil, Yuseong-gu, Daejeon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5077-4938","authenticated-orcid":true,"given":"Bu Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"R&amp;D Center, PharmAbcine Inc., 70, Yuseong-daero 1689 beon-gil, Yuseong-gu, Daejeon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunsun","family":"Park","sequence":"additional","affiliation":[{"name":"R&amp;D Center, PharmAbcine Inc., 70, Yuseong-daero 1689 beon-gil, Yuseong-gu, Daejeon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Ae","family":"Lee","sequence":"additional","affiliation":[{"name":"R&amp;D Center, PharmAbcine Inc., 70, Yuseong-daero 1689 beon-gil, Yuseong-gu, Daejeon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5188-688X","authenticated-orcid":true,"given":"Sang Ryeol","family":"Shim","sequence":"additional","affiliation":[{"name":"R&amp;D Center, PharmAbcine Inc., 70, Yuseong-daero 1689 beon-gil, Yuseong-gu, Daejeon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weon Sup","family":"Lee","sequence":"additional","affiliation":[{"name":"R&amp;D Center, PharmAbcine Inc., 70, Yuseong-daero 1689 beon-gil, Yuseong-gu, Daejeon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5834-6501","authenticated-orcid":true,"given":"Kirk M.","family":"Druey","sequence":"additional","affiliation":[{"name":"Lung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000002496"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.10.042"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2017.07.021"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2710.211155"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000005023"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.46.6129"},{"key":"e_1_3_2_8_2","first-page":"1219.e1219","article-title":"Intravenous immunoglobulins improve survival in monoclonal gammopathy-associated systemic capillary-leak syndrome","volume":"130","author":"de Chambrun M. 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