人类白细胞抗原基因座与疫苗诱导的免疫性血栓性血小板减少症的关联：血小板因子4衍生肽与MHC-II相互作用的潜在作用
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.
作者信息
Petito Eleonora, Bury Loredana, Antunes Heck Lilian, Sadler Brooke, De Candia Erica, Podda Gian Marco, Falanga Anna, Stefanini Lucia, Boccatonda Andrea, Sciancalepore Patrizia, Florio Igor, Imbalzano Egidio, Marcucci Rossella, Noris Patrizia, Panella Marta, Santoro Rita Carlotta, Turi Maria Costanza, Vaudo Gaetano, Di Paola Jorge, Rondina Matthew T, Gresele Paolo
机构信息
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.
出版信息
Br J Haematol. 2025 Jan;206(1):290-295. doi: 10.1111/bjh.19838. Epub 2024 Oct 27.
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: DPB117:01, DQA105:01, and DRB111:04. In silico analysis revealed increased affinity of DRB111:04 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.
目前尚未确定疫苗诱导的免疫性血栓性血小板减少症（VITT）的危险因素。本研究的目的是确定可能与VITT易感性相关的人类白细胞抗原（HLA）等位基因。与意大利对照组相比，VITT患者中检测到特定HLA II类等位基因的频率显著更高：DPB117:01、DQA105:01和DRB111:04。计算机分析显示，DRB111:04对血小板因子4（PF4）衍生肽ITSLEVIKA的亲和力增加，该肽包含VITT患者抗PF4抗体特异性结合位点中的两个氨基酸。我们的研究结果首次表明，对腺病毒载体疫苗产生抗PF4抗体存在遗传易感性。
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