{"doi":"10.1016/j.bvth.2024.100006","title":"Idiopathic multicentric Castleman disease - TAFRO results in high levels of mTOR activator SVEP1, tissue factor, and endotheliopathy","abstract":"Idiopathic multicentric Castleman disease (iMCD) is an inflammatory disease associated with a cytokine storm, activation of the PI3K/AKT/mTOR pathway, coagulopathy, and increased risk of thrombosis. The mechanisms underlying these pathologic processes remain elusive. We studied novel markers of mTOR activation and thrombosis in 1 patient with typical features of iMCD with TAFRO (thrombocytopenia, anasarca, fevers, reticulin myelofibrosis, and organomegaly) syndrome (iMCD-TAFRO). Plasma levels of SVEP1 (Sushi, von Willebrand factor type A, epidermal growth factor, and pentraxin domain-containing 1 protein), a newly identified mTOR activator associated with cardiovascular diseases and dementia, in addition to cytokines, chemokines and components of the coagulation cascade and complement system were evaluated by enzyme-linked immunosorbent assay (ELISA) and arrays. Compared with healthy controls, a 15-fold increase in SVEP1 was observed. High levels of factor VIIa/antithrombin and microparticles expressing functional tissue factor (TF) were detected. The anticoagulants thrombomodulin and soluble endothelial protein C receptor were elevated, indicating shedding from endothelial cells. Plasminogen activator inhibitor 1 was increased, consistent with hypofibrinolysis, whereas high levels of C3b and C5a are in keeping with complement activation. Furthermore, markers of endothelial cell activation (e.g. von Willebrand factor, angiopoietin-2), cell adhesion molecules, and angiogenesis mediators were upregulated. SVEP1 emerges as a potential mechanism of mTOR activation in iMCD-TAFRO, while multiple pathways influence coagulopathy. Immunothrombosis emerges as a potential therapeutic target for iMCD.","journal":"Blood Vessels Thrombosis & Hemostasis","year":2024,"id":479820,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9631,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1272041,"name":"Jenna Brown","orcid":"0000-0002-7789-4175","position":1,"is_corresponding":false},{"id":22803,"name":"Sara Sheikhbahaei","orcid":"0000-0001-7866-4681","position":2,"is_corresponding":false},{"id":1318859,"name":"Anne Hubben","orcid":"0000-0001-7382-2222","position":3,"is_corresponding":false},{"id":1319202,"name":"Sharon C. Liu","orcid":null,"position":4,"is_corresponding":false},{"id":256164,"name":"Keith R. McCrae","orcid":"0000-0001-7340-475X","position":5,"is_corresponding":false},{"id":230446,"name":"Shruti Chaturvedi","orcid":"0000-0001-6832-2389","position":6,"is_corresponding":false},{"id":24997,"name":"Rakhi P. Naik","orcid":"0000-0001-5562-1283","position":7,"is_corresponding":false},{"id":445383,"name":"Ivo M.B. Francischetti","orcid":"0000-0002-5764-5454","position":8,"is_corresponding":false},{"id":1319201,"name":"Chen Lossos","orcid":null,"position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:06:54.284166Z","pmid":"40191177","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":[]}