TY - JOUR
T1 - Association of human leucocyte antigen loci with vaccine-induced immune thrombotic thrombocytopenia
T2 - Potential role of the interaction between platelet factor 4-derived peptides and MHC-II
AU - Petito, Eleonora
AU - Bury, Loredana
AU - Antunes Heck, Lilian
AU - Sadler, Brooke
AU - De Candia, Erica
AU - Podda, Gian Marco
AU - Falanga, Anna
AU - Stefanini, Lucia
AU - Boccatonda, Andrea
AU - Sciancalepore, Patrizia
AU - Florio, Igor
AU - Imbalzano, Egidio
AU - Marcucci, Rossella
AU - Noris, Patrizia
AU - Panella, Marta
AU - Santoro, Rita Carlotta
AU - Turi, Maria Costanza
AU - Vaudo, Gaetano
AU - Di Paola, Jorge
AU - Rondina, Matthew T.
AU - Gresele, Paolo
N1 - Publisher Copyright:
© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
PY - 2025/1
Y1 - 2025/1
N2 - 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.
AB - 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.
KW - HLA
KW - PF4
KW - VITT
UR - http://www.scopus.com/inward/record.url?scp=85207900598&partnerID=8YFLogxK
U2 - 10.1111/bjh.19838
DO - 10.1111/bjh.19838
M3 - Article
C2 - 39462764
AN - SCOPUS:85207900598
SN - 0007-1048
VL - 206
SP - 290
EP - 295
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 1
ER -