Characterization of reverse-engineered anti-PF4 stereotypic antibodies derived from serum of patients with VITT
Jing Jing Wang, Marijn van der Neut Kolfschoten, Lucy Rutten, Bridie Armour, Chee Wee Tan, Tim Chataway, Rinke Bos, Annemart Koornneef, Pravien Abeywickrema, Rick Kapur, Leendert Porcelijn, Midia Khalifa, Ava Sadi, Pascale Bouchier, Eleni Kourkouta, Aditya Perkasa, Ted Kwaks, Roland Zahn, Laura Solforosi, Tom P. Gordon
Abstract
Letter to Blood| January 25, 2024 Characterization of reverse-engineered anti-PF4 stereotypic antibodies derived from serum of patients with VITT Jing Jing Wang, Jing Jing Wang 1Department of Immunology, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia2Department of Immunology, SA Pathology, Flinders Medical Centre, Bedford Park, SA, Australia https://orcid.org/0000-0003-0114-5570 Search for other works by this author on: This Site PubMed Google Scholar Marijn van der Neut Kolfschoten, Marijn van der Neut Kolfschoten 3Janssen Vaccines & Prevention B.V., Leiden, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar Lucy Rutten, Lucy Rutten 3Janssen Vaccines & Prevention B.V., Leiden, The Netherlands https://orcid.org/0000-0002-7363-6822 Search for other works by this author on: This Site PubMed Google Scholar Bridie Armour, Bridie Armour 1Department of Immunology, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia2Department of Immunology, SA Pathology, Flinders Medical Centre, Bedford Park, SA, Australia https://orcid.org/0000-0001-7613-1638 Search for other works by this author on: This Site PubMed Google Scholar Chee Wee Tan, Chee Wee Tan 4Department of Medicine, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia5Department of Hematology, SA Pathology, Adelaide, SA, Australia6Department of Hematology, Royal Adelaide Hospital, Central Area Local Health Network, Adelaide, SA, Australia https://orcid.org/0000-0001-8623-5991 Search for other works by this author on: This Site PubMed Google Scholar Tim Chataway, Tim Chataway 7Flinders Proteomics Facility, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia https://orcid.org/0000-0003-0254-8099 Search for other works by this author on: This Site PubMed Google Scholar Rinke Bos, Rinke Bos 3Janssen Vaccines & Prevention B.V., Leiden, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar Annemart Koornneef, Annemart Koornneef 3Janssen Vaccines & Prevention B.V., Leiden, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar Pravien Abeywickrema, Pravien Abeywickrema 8Structural & Protein Sciences, Janssen Research and Development, Spring House, PA Search for other works by this author on: This Site PubMed Google Scholar Rick Kapur, Rick Kapur 9Sanquin Research, Department of Experimental Immunohematology, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands https://orcid.org/0000-0002-1608-876X Search for other works by this author on: This Site PubMed Google Scholar Leendert Porcelijn, Leendert Porcelijn 10Department of Immunohematology Diagnostics, Sanquin Diagnostic Services, Amsterdam, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar Midia Khalifa, Midia Khalifa 3Janssen Vaccines & Prevention B.V., Leiden, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar Ava Sadi, Ava Sadi 3Janssen Vaccines & Prevention B.V., Leiden, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar Pascale Bouchier, Pascale Bouchier 3Janssen Vaccines & Prevention B.V., Leiden, The Netherlands https://orcid.org/0000-0002-9388-1809 Search for other works by this author on: This Site PubMed Google Scholar Eleni Kourkouta, Eleni Kourkouta 3Janssen Vaccines & Prevention B.V., Leiden, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar Aditya Perkasa, Aditya Perkasa 3Janssen Vaccines & Prevention B.V., Leiden, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar Ted Kwaks, Ted Kwaks 3Janssen Vaccines & Prevention B.V., Leiden, The Netherlands Search for other works by this author on: This Site PubMed Google Scholar Roland Zahn, Roland Zahn 3Janssen Vaccines & Prevention B.V., Leiden, The Netherlands https://orcid.org/0000-0003-2822-6231 Search for other works by this author on: This Site PubMed Google Scholar Laura Solforosi, Laura Solforosi 3Janssen Vaccines & Prevention B.V., Leiden, The Netherlands https://orcid.org/0000-0003-3786-6468 Search for other works by this author on: This Site PubMed Google Scholar Tom P. Gordon Tom P. Gordon 1Department of Immunology, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia2Department of Immunology, SA Pathology, Flinders Medical Centre, Bedford Park, SA, Australia https://orcid.org/0000-0003-3232-8249 Search for other works by this author on: This Site PubMed Google Scholar Blood (2024) 143 (4): 370–374. https://doi.org/10.1182/blood.2023021307 Article history Submitted: May 26, 2023 Accepted: October 31, 2023 First Edition: November 17, 2023 Connected Content A commentary has been published: Deciphering VITT's dangerous code Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Request Permissions Cite Icon Cite Search Site Citation Jing Jing Wang, Marijn van der Neut Kolfschoten, Lucy Rutten, Bridie Armour, Chee Wee Tan, Tim Chataway, Rinke Bos, Annemart Koornneef, Pravien Abeywickrema, Rick Kapur, Leendert Porcelijn, Midia Khalifa, Ava Sadi, Pascale Bouchier, Eleni Kourkouta, Aditya Perkasa, Ted Kwaks, Roland Zahn, Laura Solforosi, Tom P. Gordon; Characterization of reverse-engineered anti-PF4 stereotypic antibodies derived from serum of patients with VITT. Blood 2024; 143 (4): 370–374. doi: https://doi.org/10.1182/blood.2023021307 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBlood Search Subjects: Thrombosis and Hemostasis TO THE EDITOR: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a complex multifactorial medical condition observed rarely following vaccination with adenovirus-based coronavirus disease 2019 (COVID-19) vaccines,1-6 and also after other types of vaccines.7-9 VITT involves platelet factor 4 (PF4) autoimmunity, which is also observed in heparin-induced thrombocytopenia.10-12 However, it is now known that VITT and heparin-induced thrombocytopenia antibodies bind separate epitopes on PF4 and have distinct clonal profiles.13-15 We recently discovered highly stereotypic anti-PF4 antibodies in 5 patients with VITT after ChAdOx1 nCoV-19 vaccination using mass spectrometry–based proteomics. These unique serum clonotypes are specified by identical IGLV3-21∗02 allelic light chains paired with heavy chains expressing shared heavy chain third complementarity–determining region (HCDR)3 amino acids motifs. These findings shed light on... References 1.Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med. 2021;384(22):2092-2101.Google ScholarCrossrefSearch ADS 2.Schultz NH, Sørvoll IH, Michelsen AE, et al. Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination. N Engl J Med. 2021;384(22):2124-2130.Google ScholarCrossrefSearch ADS 3.Scully M, Singh D, Lown R, et al. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination. N Engl J Med. 2021;384(23):2202-2211.Google ScholarCrossrefSearch ADS 4.Abrams CS, Barnes GD. SARS-CoV-2 vaccination-induced thrombotic thrombocytopenia: a rare but serious immunologic complication. 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