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.

IF 5.1 2区医学 Q1 HEMATOLOGY

British Journal of Haematology Pub Date : 2024-10-27 DOI:10.1111/bjh.19838

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

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引用次数: 0

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.

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人类白细胞抗原位点与疫苗诱导的免疫性血小板减少症的关系：血小板因子 4 衍生肽与 MHC-II 之间相互作用的潜在作用。

迄今为止，尚未发现疫苗诱发免疫性血栓性血小板减少症（VITT）的风险因素。本研究旨在确定可能与 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，在 VITT 患者中检测到的特定 HLA II 类等位基因的频率明显更高：DPB1*17:01、DQA1*05:01 和 DRB1*11:04。硅学分析表明，DRB1*11:04 与血小板因子 4（PF4）衍生的多肽 ITSLEVIKA 的亲和力增强，ITSLEVIKA 含有两个氨基酸，存在于 VITT 患者抗 PF4 抗体的特异性结合位点。我们的研究结果首次显示了一种遗传易感性，这种易感性会在接种广告载体疫苗后产生抗 PF4 抗体。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

British Journal of Haematology 医学-血液学

CiteScore

8.60

自引率

4.60%

发文量

565

审稿时长

1 months

期刊介绍： The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.