Association of human leucocyte antigen loci with vaccine‐induced immune thrombotic thrombocytopenia: Potential role of the interaction between platelet factor 4‐derived peptides and <scp>MHC</scp>‐<scp>II</scp>
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 Santoro, Maria Costanza Turi, Gaetano Vaudo, Jorge Di Paola, Matthew T. Rondina, Paolo Gresele
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.