Association of human leucocyte antigen loci with vaccine-induced immune thrombotic thrombocytopenia: Potential role of the interaction between platelet factor 4-derived peptides and MHC-II.

Rossella Marcucci, Maria Costanza Turi, Rita Carlotta Santoro, Igor Florio, Patrizia Sciancalepore, Gian Marco Podda, Lilian Antunes Heck, Loredana Bury, Eleonora Petito, Marta Panella, Andrea Boccatonda, Brooke Sadler, Egidio Imbalzano, Anna Falanga, Matthew T Rondina, Lucia Stefanini, Paolo Gresele, Gaetano Vaudo, Erica De Candia, Jorge Di Paola, Patrizia Noris

Journal: British journal of haematology 2025;206(1):290-295

PMID: 39462764

Abstract

No risk factors have been identified for vaccine-induced immune thrombotic thrombocytopenia (VITT) so far. The aim of this study was to identify human leucocyte antigen (HLA) alleles potentially associated with VITT susceptibility. Specific HLA class II alleles were detected with significantly higher frequency in VITT patients compared with Italian controls: DPB1*17:01, DQA1*05:01, and DRB1*11:04. In silico analysis revealed increased affinity of DRB1*11:04 for a platelet factor 4 (PF4)-derived peptide, ITSLEVIKA, that contains two amino acids present in the specific binding site of anti-PF4 antibodies from VITT patients. Our findings show for the first time a genetic predisposition to developing anti-PF4 antibodies in response to Ad-vector vaccines.

© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

Address: Section of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.; Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.; Hemorrhagic and Thrombotic Diseases Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.; Medicina III, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milano, Italy.; Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy.; Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.; Internal Medicine, Azienda USL di Bologna, Bologna, Italy.; Haemostasis and Thrombosis Center, Azienda Ospedaliera SS. Antonio e Biagio, Alessandria, Italy.; Unit of Neurology and Stroke Unit, Azienda Ospedaliera di Bolzano, Bolzano, Italy.; Section of Internal Medicine, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.; Department of Clinical and Experimental Medicine, University of Florence, Firenze, Italy.; Department of Internal Medicine, University of Pavia, Pavia, Italy.; IRCCS Policlinico San Matteo Foundation, Pavia, Italy.; Department of Neuroscience, University Hospital of tor Vergata, Rome, Italy.; Haemophilia and Thrombosis Center, Pugliese-Ciaccio Hospital, Catanzaro, Italy.; Division of Pulmonary Disease, SS. Annunziata Hospital of Chieti, Chieti, Italy.; Unit of Internal Medicine, Terni University Hospital, Terni, Italy.; Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah Health, Salt Lake City, Utah, USA.; Division of Microbiology and Immunology, The Department of Pathology, University of Utah Health, Salt Lake City, Utah, USA.; University of Utah Molecular Medicine Program, University of Utah Health, Salt Lake City, Utah, USA.; The Department of Medicine and the Geriatric Research, Education, and Clinical Center (GRECC), George E. Wahlen VAMC, Salt Lake City, Utah, USA.
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