Proteomic Profiling and T Cell Receptor Usage of Abacavir Susceptible Subjects

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)...

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Published in:Biomedicines 2022-03, Vol.10 (3), p.693
Main Authors: Gall, Eline, Stieglitz, Florian, Pich, Andreas, Behrens, Georg Martin Norbert, Kuhn, Joachim, Blasczyk, Rainer, Haukamp, Funmilola Josephine, Bade-Döding, Christina
Format: Article
Language:English
Subjects:
Abacavir
adverse drug reaction
Antigen presentation
Antigens
Antiretroviral agents
Effector cells
FDA approval
Genotypes
Histocompatibility antigen HLA
HIV
HLA-B57:01
Human immunodeficiency virus
Hypersensitivity
Immune system
Interferon
Lymphocytes
Lymphocytes T
Pathogens
Patients
Peptides
Product safety
proteome
Proteomes
Proteomics
T cell receptor
T cell receptors
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Summary: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-B*57:01 and discriminates HLA-B*57:01 HIV patients from ABC treatment. However, not all HLA-B*57:01 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-B*57:01 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.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines10030693