Characterization of T-Cell Responses to SMX and SMX-NO in Co-Trimoxazole Hypersensitivity Patients Expressing HLA-B*13:01
HLA-B*13:01-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 sy...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2021-04-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.658593/full |
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doaj-03d26c6a0de240ce8c0bfdad4c177587 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jirawat Pratoomwun Jirawat Pratoomwun Paul Thomson Kanoot Jaruthamsophon Rawiporn Tiyasirichokchai Pimonpan Jinda Ticha Rerkpattanapipat Wichittra Tassaneeyakul Nontaya Nakkam Pawinee Rerknimitr Jettanong Klaewsongkram Yuttana Srinoulprasert Munir Pirmohamed Dean J. Naisbitt Chonlaphat Sukasem |
spellingShingle |
Jirawat Pratoomwun Jirawat Pratoomwun Paul Thomson Kanoot Jaruthamsophon Rawiporn Tiyasirichokchai Pimonpan Jinda Ticha Rerkpattanapipat Wichittra Tassaneeyakul Nontaya Nakkam Pawinee Rerknimitr Jettanong Klaewsongkram Yuttana Srinoulprasert Munir Pirmohamed Dean J. Naisbitt Chonlaphat Sukasem Characterization of T-Cell Responses to SMX and SMX-NO in Co-Trimoxazole Hypersensitivity Patients Expressing HLA-B*13:01 Frontiers in Immunology co-trimoxazole drug hypersensitivity human leukocyte antigen sulfamethoxazole T cell |
author_facet |
Jirawat Pratoomwun Jirawat Pratoomwun Paul Thomson Kanoot Jaruthamsophon Rawiporn Tiyasirichokchai Pimonpan Jinda Ticha Rerkpattanapipat Wichittra Tassaneeyakul Nontaya Nakkam Pawinee Rerknimitr Jettanong Klaewsongkram Yuttana Srinoulprasert Munir Pirmohamed Dean J. Naisbitt Chonlaphat Sukasem |
author_sort |
Jirawat Pratoomwun |
title |
Characterization of T-Cell Responses to SMX and SMX-NO in Co-Trimoxazole Hypersensitivity Patients Expressing HLA-B*13:01 |
title_short |
Characterization of T-Cell Responses to SMX and SMX-NO in Co-Trimoxazole Hypersensitivity Patients Expressing HLA-B*13:01 |
title_full |
Characterization of T-Cell Responses to SMX and SMX-NO in Co-Trimoxazole Hypersensitivity Patients Expressing HLA-B*13:01 |
title_fullStr |
Characterization of T-Cell Responses to SMX and SMX-NO in Co-Trimoxazole Hypersensitivity Patients Expressing HLA-B*13:01 |
title_full_unstemmed |
Characterization of T-Cell Responses to SMX and SMX-NO in Co-Trimoxazole Hypersensitivity Patients Expressing HLA-B*13:01 |
title_sort |
characterization of t-cell responses to smx and smx-no in co-trimoxazole hypersensitivity patients expressing hla-b*13:01 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-04-01 |
description |
HLA-B*13:01-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 HLA-B*13:01. Sulfamethoxazole and nitroso sulfamethoxazole specific T cell clones were generated from T cell lines of co-trimoxazole hypersensitive HLA-B*13:01-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 via 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 via 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 HLA-B*13:01 is not directly involved in the iatrogenic disease observed in co-trimoxazole hypersensitivity patients. |
topic |
co-trimoxazole drug hypersensitivity human leukocyte antigen sulfamethoxazole T cell |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.658593/full |
work_keys_str_mv |
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doaj-03d26c6a0de240ce8c0bfdad4c1775872021-04-29T13:43:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.658593658593Characterization of T-Cell Responses to SMX and SMX-NO in Co-Trimoxazole Hypersensitivity Patients Expressing HLA-B*13:01Jirawat Pratoomwun0Jirawat Pratoomwun1Paul Thomson2Kanoot Jaruthamsophon3Rawiporn Tiyasirichokchai4Pimonpan Jinda5Ticha Rerkpattanapipat6Wichittra Tassaneeyakul7Nontaya Nakkam8Pawinee Rerknimitr9Jettanong Klaewsongkram10Yuttana Srinoulprasert11Munir Pirmohamed12Dean J. Naisbitt13Chonlaphat Sukasem14Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandDepartment of Clinical Chemistry, Faculty of Medical Technology, Huachiew Chalermprakiet University, Samut Prakan, ThailandMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United KingdomDivision of Human Genetics, Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat Yai, ThailandDivision of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandDivision of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandDivision of Allergy Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandDepartment of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDepartment of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDivision of Dermatology, Department of Medicine, Faculty of Medicine, Skin and Allergy Research Unit, Chulalongkorn University, Bangkok, ThailandSkin and Allergy Research Unit, Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandDepartment of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United KingdomMRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United KingdomDivision of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandHLA-B*13:01-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 HLA-B*13:01. Sulfamethoxazole and nitroso sulfamethoxazole specific T cell clones were generated from T cell lines of co-trimoxazole hypersensitive HLA-B*13:01-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 via 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 via 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 HLA-B*13:01 is not directly involved in the iatrogenic disease observed in co-trimoxazole hypersensitivity patients.https://www.frontiersin.org/articles/10.3389/fimmu.2021.658593/fullco-trimoxazoledrug hypersensitivityhuman leukocyte antigensulfamethoxazoleT cell |