{"doi":"10.1126/sciadv.adi1394","title":"A ligand-independent Tie2-activating antibody reduces vascular leakage in models of Clarkson disease","abstract":"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.","journal":"Science Advances","year":2023,"id":345310,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":516543,"name":"Abhishek Desai","orcid":"0000-0002-6770-4876","position":1,"is_corresponding":false},{"id":1084784,"name":"Jin-San Yoo","orcid":"0000-0003-2695-9685","position":2,"is_corresponding":false},{"id":1085301,"name":"Cheon Ho Park","orcid":null,"position":3,"is_corresponding":false},{"id":1085302,"name":"Eun-Ah Lee","orcid":null,"position":4,"is_corresponding":false},{"id":1085303,"name":"Bu Yeon Kim","orcid":null,"position":5,"is_corresponding":false},{"id":1084785,"name":"Hyunsun Park","orcid":"0000-0003-1338-654X","position":6,"is_corresponding":false},{"id":213824,"name":"Young Ae Lee","orcid":null,"position":7,"is_corresponding":false},{"id":1084786,"name":"Sang Ryeol Shim","orcid":"0000-0002-5188-688X","position":8,"is_corresponding":false},{"id":1085304,"name":"Weon Sup Lee","orcid":null,"position":9,"is_corresponding":false},{"id":369508,"name":"Kirk M. Druey","orcid":"0000-0002-5834-6501","position":10,"is_corresponding":false},{"id":1084783,"name":"Ararat J. Ablooglu","orcid":"0009-0002-8692-4572","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T01:11:39.484741Z","pmid":"37976351","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}