Characterization of T-Cell Responses to SMX and SMX-NO in Co-Trimoxazole Hypersensitivity Patients Expressing <i>HLA-B*13:01</i>



Pratoomwun, Jirawat, Thomson, Paul ORCID: 0000-0001-5431-0459, Jaruthamsophon, Kanoot, Tiyasirichokchai, Rawiporn, Jinda, Pimonpan, Rerkpattanapipat, Ticha, Tassaneeyakul, Wichittra, Nakkam, Nontaya, Rerknimitr, Pawinee, Klaewsongkram, Jettanong
et al (show 4 more authors) (2021) Characterization of T-Cell Responses to SMX and SMX-NO in Co-Trimoxazole Hypersensitivity Patients Expressing <i>HLA-B*13:01</i>. FRONTIERS IN IMMUNOLOGY, 12. 658593-.

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Abstract

<i>HLA-B*13:01</i>-positive patients in Thailand can develop frequent co-trimoxazole hypersensitivity reactions. This study aimed to characterize drug-specific T cells from three co-trimoxazole hypersensitive patients presenting with either Stevens-Johnson syndrome or drug reaction with eosinophilia and systemic symptoms. Two of the patients carried the HLA allele of interest, namely <i>HLA-B*13:01</i>. Sulfamethoxazole and nitroso sulfamethoxazole specific T cell clones were generated from T cell lines of co-trimoxazole hypersensitive <i>HLA-B*13:01</i>-positive patients. Clones were characterized for antigen specificity and cross-reactivity with structurally related compounds by measuring proliferation and cytokine release. Surface marker expression was characterized <i>via</i> flow cytometry. Mechanistic studies were conducted to assess pathways of T cell activation in response to antigen stimulation. Peripheral blood mononuclear cells from all patients were stimulated to proliferate and secrete IFN-γ with nitroso sulfamethoxazole. All sulfamethoxazole and nitroso sulfamethoxazole specific T cell clones expressed the CD4+ phenotype and strongly secreted IL-13 as well as IFN-γ, granzyme B and IL-22. No secretion of IL-17 was observed. A number of nitroso sulfamethoxazole-specific clones cross-reacted with nitroso dapsone but not sulfamethoxazole whereas sulfamethoxazole specific clones cross-reacted with nitroso sulfamethoxazole only. The nitroso sulfamethoxazole specific clones were activated in both antigen processing-dependent and -independent manner, while sulfamethoxazole activated T cell responses <i>via</i> direct HLA binding. Furthermore, activation of nitroso sulfamethoxazole-specific, but not sulfamethoxazole-specific, clones was blocked with glutathione. Sulfamethoxazole and nitroso sulfamethoxazole specific T cell clones from hypersensitive patients were CD4+ which suggests that <i>HLA-B*13:01</i> is not directly involved in the iatrogenic disease observed in co-trimoxazole hypersensitivity patients.

Item Type: Article
Uncontrolled Keywords: co-trimoxazole, drug hypersensitivity, human leukocyte antigen, sulfamethoxazole, T cell
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 01 Jun 2021 14:49
Last Modified: 18 Oct 2023 08:37
DOI: 10.3389/fimmu.2021.658593
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3124660