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阿巴卡韦敏感受试者的蛋白质组分析和T细胞受体使用情况

Proteomic Profiling and T Cell Receptor Usage of Abacavir Susceptible Subjects.

作者信息

Gall Eline, Stieglitz Florian, Pich Andreas, Behrens Georg Martin Norbert, Kuhn Joachim, Blasczyk Rainer, Haukamp Funmilola Josephine, Bade-Döding Christina

机构信息

Institute for Transfusion Medicine and Transplantat Engineering, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.

Institute of Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.

出版信息

Biomedicines. 2022 Mar 17;10(3):693. doi: 10.3390/biomedicines10030693.

DOI:10.3390/biomedicines10030693
PMID:35327495
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8945713/
Abstract

Type B adverse drug reactions (ADRs) represent a significant threat as their occurrence arises unpredictable and despite proper application of the drug. The severe immune reaction Abacavir Hypersensitivity Syndrome (AHS) that arises in HIV patients treated with the antiretroviral drug Abacavir (ABC) strongly correlates to the presence of the human leukocyte antigen (HLA) genotype HLA-B57:01 and discriminates HLA-B57:01 HIV patients from ABC treatment. However, not all HLA-B57:01 HIV patients are affected by AHS, implying the involvement of further patient-specific factors in the development of AHS. The establishment of a reliable assay to classify HLA-B57:01 carriers as ABC sensitive or ABC tolerant allowed to investigate the T cell receptor (TCR) Vβ chain repertoire of effector cells and revealed Vβ6 and Vβ24 as potential public TCRs in ABC sensitive HLA-B*57:01 carriers. Furthermore, distinct effects of ABC on the cellular proteome of ABC sensitive and tolerant volunteers were observed and suggest enhanced activation and maturation of dentritic cells (DC) in ABC sensitive volunteers. Analysis of ABC-naïve cellular proteomes identified the T cell immune regulator 1 (TCIRG1) as a potential prognostic biomarker for ABC susceptibility and the involvement of significantly upregulated proteins, particularly in peptide processing, antigen presentation, interferon (IFN), and cytokine regulation.

摘要

B型药物不良反应（ADR）是一个重大威胁，因为其发生不可预测，且尽管药物使用得当仍会出现。接受抗逆转录病毒药物阿巴卡韦（ABC）治疗的HIV患者中出现的严重免疫反应阿巴卡韦超敏综合征（AHS）与人类白细胞抗原（HLA）基因型HLA - B57:01密切相关，并将携带HLA - B57:01的HIV患者与ABC治疗区分开来。然而，并非所有携带HLA - B57:01的HIV患者都会受到AHS影响，这意味着AHS的发生还涉及其他患者特异性因素。建立一种可靠的检测方法，将HLA - B57:01携带者分类为对ABC敏感或耐受，从而能够研究效应细胞的T细胞受体（TCR）Vβ链库，并揭示Vβ6和Vβ24是对ABC敏感的HLA - B*57:01携带者中潜在的公共TCR。此外，观察到ABC对ABC敏感和耐受志愿者细胞蛋白质组有不同影响，这表明ABC敏感志愿者中树突状细胞（DC）的激活和成熟增强。对未接触过ABC的细胞蛋白质组分析确定T细胞免疫调节因子1（TCIRG1）是ABC易感性的潜在预后生物标志物，且有显著上调的蛋白质参与其中，特别是在肽加工、抗原呈递、干扰素（IFN）和细胞因子调节方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9f3/8945713/1e390441881e/biomedicines-10-00693-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9f3/8945713/1e390441881e/biomedicines-10-00693-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9f3/8945713/067899714a77/biomedicines-10-00693-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9f3/8945713/fcb00d0801f0/biomedicines-10-00693-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9f3/8945713/07bfed4a23f2/biomedicines-10-00693-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9f3/8945713/b491fdfeb7ca/biomedicines-10-00693-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9f3/8945713/1e390441881e/biomedicines-10-00693-g007.jpg

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