{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:16:12Z","timestamp":1790486172473,"version":"4.1.0"},"reference-count":54,"publisher":"American Society of Hematology","issue":"23","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Thromboembolism complicates disorders caused by immunoglobulin G (IgG)\u2013containing immune complexes (ICs), but the underlying mechanisms are incompletely understood. Prior evidence indicates that induction of tissue factor (TF) on monocytes, a pivotal step in the initiation, localization, and propagation of coagulation by ICs, is mediated through Fc\u03b3 receptor IIa (Fc\u03b3RIIa); however, the involvement of other receptors has not been investigated in detail. The neonatal Fc receptor (FcRn) that mediates IgG and albumin recycling also participates in cellular responses to IgG-containing ICs. Here we asked whether FcRn is also involved in the induction of TF-dependent factor Xa (FXa) activity by IgG-containing ICs by THP-1 monocytic cells and human monocytes. Induction of FXa activity by ICs containing IgG antibodies to platelet factor 4 (PF4) involved in heparin-induced thrombocytopenia (HIT), \u03b2-2-glycoprotein-1 implicated in antiphospholipid syndrome, or red blood cells coated with anti-(\u03b1)-Rh(D) antibodies that mediate hemolysis in vivo was inhibited by a humanized monoclonal antibody (mAb) that blocks IgG binding to human FcRn. IgG-containing ICs that bind to Fc\u03b3R and FcRn induced FXa activity, whereas IgG-containing ICs with an Fc engineered to be unable to engage FcRn did not. Infusion of an \u03b1-FcRn mAb prevented fibrin deposition after microvascular injury in a murine model of HIT in which human Fc\u03b3RIIa was expressed as a transgene. These data implicate FcRn in TF-dependent FXa activity induced by soluble and cell-associated IgG-containing ICs. Antibodies to FcRn, now in clinical trials in warm autoimmune hemolytic anemia to lower IgG antibodies and IgG containing ICs may also reduce the risk of venous thromboembolism.<\/jats:p>","DOI":"10.1182\/blood.2019001133","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T19:00:02Z","timestamp":1584558002000},"page":"2085-2093","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":37,"title":["FcRn augments induction of tissue factor activity by IgG-containing immune complexes"],"prefix":"10.1182","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5986-504X","authenticated-orcid":false,"given":"Douglas B.","family":"Cines","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and"},{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei","family":"Zaitsev","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1990-3077","authenticated-orcid":false,"given":"Lubica","family":"Rauova","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann H.","family":"Rux","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9313-5742","authenticated-orcid":false,"given":"Victoria","family":"Stepanova","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6381-4325","authenticated-orcid":false,"given":"Sriram","family":"Krishnaswamy","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita","family":"Sarkar","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Anna","family":"Kowalska","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohua","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3740-0318","authenticated-orcid":false,"given":"Alan E.","family":"Mast","sequence":"first","affiliation":[{"name":"Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI;"},{"name":"Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9704-248X","authenticated-orcid":false,"given":"Laurence J.","family":"Blumberg","sequence":"first","affiliation":[{"name":"Syntimmune, Inc., Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7340-475X","authenticated-orcid":false,"given":"Keith R.","family":"McCrae","sequence":"first","affiliation":[{"name":"Taussig Cancer Institute and"},{"name":"Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7237-3613","authenticated-orcid":false,"given":"Mortimer","family":"Poncz","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 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