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

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

doi:10.1111/bjh.19838

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

Br J Haematol. 2024 Oct 27. doi: 10.1111/bjh.19838. Online ahead of print.

Authors

Eleonora Petito¹, Loredana Bury¹, Lilian Antunes Heck², Brooke Sadler², Erica De Candia³, Gian Marco Podda⁴, Anna Falanga⁵, Lucia Stefanini⁶, Andrea Boccatonda⁷, Patrizia Sciancalepore⁸, Igor Florio⁹, Egidio Imbalzano¹⁰, Rossella Marcucci¹¹, Patrizia Noris^{12

13}, Marta Panella¹⁴, Rita Carlotta Santoro¹⁵, Maria Costanza Turi¹⁶, Gaetano Vaudo¹⁷, Jorge Di Paola², Matthew T Rondina^{18

19

20

21}, Paolo Gresele¹

Affiliations

¹ Section of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
² Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
³ Hemorrhagic and Thrombotic Diseases Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁴ Medicina III, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milano, Italy.
⁵ Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy.
⁶ Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
⁷ Internal Medicine, Azienda USL di Bologna, Bologna, Italy.
⁸ Haemostasis and Thrombosis Center, Azienda Ospedaliera SS. Antonio e Biagio, Alessandria, Italy.
⁹ Unit of Neurology and Stroke Unit, Azienda Ospedaliera di Bolzano, Bolzano, Italy.
¹⁰ Section of Internal Medicine, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
¹¹ Department of Clinical and Experimental Medicine, University of Florence, Firenze, Italy.
¹² Department of Internal Medicine, University of Pavia, Pavia, Italy.
¹³ IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
¹⁴ Department of Neuroscience, University Hospital of tor Vergata, Rome, Italy.
¹⁵ Haemophilia and Thrombosis Center, Pugliese-Ciaccio Hospital, Catanzaro, Italy.
¹⁶ Division of Pulmonary Disease, SS. Annunziata Hospital of Chieti, Chieti, Italy.
¹⁷ Unit of Internal Medicine, Terni University Hospital, Terni, Italy.
¹⁸ Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah Health, Salt Lake City, Utah, USA.
¹⁹ Division of Microbiology and Immunology, The Department of Pathology, University of Utah Health, Salt Lake City, Utah, USA.
²⁰ University of Utah Molecular Medicine Program, University of Utah Health, Salt Lake City, Utah, USA.
²¹ The Department of Medicine and the Geriatric Research, Education, and Clinical Center (GRECC), George E. Wahlen VAMC, Salt Lake City, Utah, USA.

PMID: 39462764
DOI: 10.1111/bjh.19838

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.

Keywords: HLA; PF4; VITT.

Grants and funding

Fondazione Umberto Veronesi