Portal de Periódicos da CAPES

Vaccine-induced immune thrombotic thrombocytopenia is mediated by a stereotyped clonotypic antibody

2022; Elsevier BV; Volume: 140; Issue: 15 Linguagem: Inglês

10.1182/blood.2022016474

1528-0020

Jing Jing Wang, Bridie Armour, Tim Chataway, Alexander Troelnikov, Alex D. Colella, Olivia Yacoub, Simon Hockley, Chee Wee Tan, Tom P. Gordon,

Blood groups and transfusion

Letter to Blood| October 13, 2022 Vaccine-induced immune thrombotic thrombocytopenia is mediated by a stereotyped clonotypic antibody Jing Jing Wang, Jing Jing Wang 1Department of Immunology, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia2Department of Immunology, South Australia (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 Bridie Armour, Bridie Armour 1Department of Immunology, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia2Department of Immunology, South Australia (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 Tim Chataway, Tim Chataway 3Flinders 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 Alexander Troelnikov, Alexander Troelnikov 1Department of Immunology, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia2Department of Immunology, South Australia (SA) Pathology (Flinders Medical Centre), Bedford Park, SA, Australia https://orcid.org/0000-0002-7239-3814 Search for other works by this author on: This Site PubMed Google Scholar Alex Colella, Alex Colella 3Flinders Proteomics Facility, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Olivia Yacoub, Olivia Yacoub 4SA Pathology, Adelaide, SA, Australia https://orcid.org/0000-0001-8817-9591 Search for other works by this author on: This Site PubMed Google Scholar Simon Hockley, Simon Hockley 5Intensive Care Unit, Calvary Hospital, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Chee Wee Tan, Chee Wee Tan 4SA Pathology, Adelaide, SA, Australia6Department of Haematology, Royal Adelaide Hospital, Central Area Local Health Network (CALHN), Adelaide, SA, Australia https://orcid.org/0000-0001-8623-5991 Search for other works by this author on: This Site PubMed Google Scholar Tom Paul Gordon Tom Paul Gordon 1Department of Immunology, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia2Department of Immunology, South Australia (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 (2022) 140 (15): 1738–1742. https://doi.org/10.1182/blood.2022016474 Article history Submitted: March 28, 2022 Accepted: May 31, 2022 First Edition: June 3, 2022 Connected Content This is a related article to: Dangerous B-cell clones An erratum has been published: Wang JJ, Armour B, Chataway T, et al. Vaccine-induced immune thrombotic thrombocytopenia is mediated by a stereotyped clonotypic antibody. Blood. 2022;140(15):1738-1742. Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Request Permissions Cite Icon Cite Search Site Citation Jing Jing Wang, Bridie Armour, Tim Chataway, Alexander Troelnikov, Alex Colella, Olivia Yacoub, Simon Hockley, Chee Wee Tan, Tom Paul Gordon; Vaccine-induced immune thrombotic thrombocytopenia is mediated by a stereotyped clonotypic antibody. Blood 2022; 140 (15): 1738–1742. doi: https://doi.org/10.1182/blood.2022016474 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: Free Research Articles, Immunobiology and Immunotherapy, Thrombosis and Hemostasis TO THE EDITOR: The syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare thromboembolic complication of adenoviral-vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson) mediated by antibodies directed against platelet factor 4 (PF4).1-5 The mechanisms by which the adenoviral DNA vectors break immune tolerance to PF4 and trigger B-cell clonal expansion and secretion of anti-PF4 immunoglobulin Gs (IgGs) are under intense investigation and likely involve formation of immunogenic complexes of PF4 with vaccine components in a proinflammatory setting.6 Pathogenic anti-PF4 IgGs subsequently form circulating immune complexes with PF4 tetramers, which are thought to drive thrombotic events by Fc γ receptor IIa–dependent platelet activation and to activate granulocytes to release procoagulant neutrophil extracellular traps.6-8 Serum anti-PF4 antibodies are mostly transient and appear in serum within days of vaccination, suggesting... 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.Costello A, Pandita A, Devitt J. Case report: thrombotic thrombocytopenia after COVID-19 Janssen vaccination. Am Fam Physician. 2021;103(11):646-647.Google ScholarPubMed 5.Muir KL, Kallam A, Koepsell SA, Gundabolu K. Thrombotic thrombocytopenia after Ad26.COV2.S vaccination. N Engl J Med. 2021;384(20):1964-1965.Google ScholarCrossrefSearch ADS 6.Greinacher A, Selleng K, Palankar R, et al. Insights in ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopenia. Blood. 2021;138(22):2256-2268.Google ScholarCrossrefSearch ADS PubMed 7.Baker AT, Boyd RJ, Sarkar D, et al. ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome. Sci Adv. 2021;7(49):eabl8213.Google ScholarCrossrefSearch ADS PubMed 8.Greinacher A, Schönborn L, Siegerist F, et al. Pathogenesis of vaccine-induced immune thrombotic thrombocytopenia (VITT). Semin Hematol. 2022;59(2):97-107.Google ScholarCrossrefSearch ADS PubMed 9.Schönborn L, Thiele T, Kaderali L, Greinacher A. Decline in pathogenic antibodies over time in VITT. N Engl J Med. 2021;385(19):1815-1816.Google ScholarCrossrefSearch ADS 10.Huynh A, Kelton JG, Arnold DM, Daka M, Nazy I. Antibody epitopes in vaccine-induced immune thrombotic thrombocytopaenia. Nature. 2021;596(7873):565-569.Google ScholarCrossrefSearch ADS PubMed 11.Singh B, Kanack A, Bayas A, et al. Anti-PF4 VITT antibodies are oligoclonal and variably inhibited by heparin. medRxiv. 2021.Google Scholar 12.Singh B, Kanack A, Bayas A, et al. Monoclonal and oligoclonal anti-PF4 antibodies mediate VITT. [abstract]. Blood. 2021;138(suppl 1). Abstract 3220.Google Scholar 13.Wang JJ, Al Kindi MA, Colella AD, et al. IgV peptide mapping of native Ro60 autoantibody proteomes in primary Sjögren’s syndrome reveals molecular markers of Ro/La diversification. Clin Immunol. 2016;173:57-63.Google ScholarCrossrefSearch ADS PubMed 14.Al Kindi MA, Colella AD, Chataway TK, Jackson MW, Wang JJ, Gordon TP. Secreted autoantibody repertoires in Sjögren’s syndrome and systemic lupus erythematosus: a proteomic approach. Autoimmun Rev. 2016;15(4):405-410.Google ScholarCrossrefSearch ADS PubMed 15.Wang JJ, Colella AD, Beroukas D, Chataway TK, Gordon TP. Precipitating anti-dsDNA peptide repertoires in lupus. Clin Exp Immunol. 2018;194(3):273-282.Google ScholarCrossrefSearch ADS PubMed 16.Wang JJ, Reed JH, Colella AD, et al. Molecular profiling and clonal tracking of secreted rheumatoid factors in primary Sjögren’s syndrome. Arthritis Rheumatol. 2018;70(10):1617-1625.Google ScholarCrossrefSearch ADS PubMed 17.Greinacher A, Selleng K, Mayerle J, et al. Immune-Response in COVID-19 Vaccination Study Group. Anti-platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein. Blood. 2021;138(14):1269-1277.Google ScholarCrossrefSearch ADS PubMed 18.Arepally GM, Kamei S, Park KS, et al. Characterization of a murine monoclonal antibody that mimics heparin-induced thrombocytopenia antibodies. Blood. 2000;95(5):1533-1540.Google ScholarCrossrefSearch ADS PubMed 19.Maity PC, Bilal M, Koning MT, et al. IGLV3-21∗01 is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling. Proc Natl Acad Sci USA. 2020;117(8):4320-4327.Google ScholarCrossrefSearch ADS PubMed 20.Xu JL, Davis MM. Diversity in the CDR3 region of V(H) is sufficient for most antibody specificities. Immunity. 2000;13(1):37-45.Google ScholarCrossrefSearch ADS PubMed 21.Thurgood LA, Arentz G, Lindop R, et al. An immunodominant La/SSB autoantibody proteome derives from public clonotypes. Clin Exp Immunol. 2013;174(2):237-244.Google ScholarCrossrefSearch ADS PubMed 22.Merlini G, Stone MJ. Dangerous small B-cell clones. Blood. 2006;108(8):2520-2530.Google ScholarCrossrefSearch ADS PubMed 23.Huynh A, Arnold DM, Michael JV, et al. Characteristics of VITT antibodies in patients vaccinated with Ad26.COV2.S. [published online ahead of print 4 April 2022]. Blood Adv. 2022. https://doi.org/10.1182/bloodadvances.2022007336Google Scholar 24.Singh M, Jackson KJL, Wang JJ, et al. Lymphoma driver mutations in the pathogenic evolution of an iconic human autoantibody. Cell. 2020;180(5):878-894.e19.Google ScholarCrossrefSearch ADS PubMed 25.Wheatley AK, Juno JA, Wang JJ, et al. Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19. Nat Commun. 2021;12(1162):1-11.Google ScholarPubMed © 2022 by The American Society of Hematology2022 © 2022 by The American Society of Hematology2022 You do not currently have access to this content. Sign in via your Institution