Proteomic Profiling and T Cell Receptor Usage of Abacavir Susceptible Subjects

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2022 Mar 25

PMID 35327495

Authors

Eline Gall

Florian Stieglitz

Andreas Pich

Georg Martin Norbert Behrens

Joachim Kuhn

Rainer Blasczyk

Funmilola Josephine Haukamp

Christina Bade-Doding

Affiliations

Soon will be listed here.

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-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.

Citing Articles

HLA-B*57:01/Carbamazepine-10,11-Epoxide Association Triggers Upregulation of the NFκB and JAK/STAT Pathways.

Haukamp F, Hartmann Z, Pich A, Kuhn J, Blasczyk R, Stieglitz F Cells. 2023; 12(5).

PMID: 36899812 PMC: 10000580. DOI: 10.3390/cells12050676.

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