Drug-specific CD4(+) T-cell immune responses are responsible for antituberculosis drug-induced maculopapular exanthema and drug reaction with eosinophilia and systemic symptoms syndrome
DC Field | Value | Language |
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dc.contributor.author | Ye, Y. -M. | - |
dc.contributor.author | Hur, G. -Y. | - |
dc.contributor.author | Kim, S. -H. | - |
dc.contributor.author | Ban, G. -Y. | - |
dc.contributor.author | Jee, Y. -K. | - |
dc.contributor.author | Naisbitt, D. J. | - |
dc.contributor.author | Park, H. -S. | - |
dc.contributor.author | Kim, S. -H. | - |
dc.date.accessioned | 2021-09-03T10:28:59Z | - |
dc.date.available | 2021-09-03T10:28:59Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2017-02 | - |
dc.identifier.issn | 0007-0963 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/84793 | - |
dc.description.abstract | Background A multidrug regimen including isoniazid, rifampicin, pyrazinamide and ethambutol is commonly used as first-line treatment for tuberculosis. However, this regimen can occasionally result in severe adverse drug reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and drug-induced liver injury. The culprit drug and mechanistic basis for the hypersensitive reaction are unknown. Objectives To investigate drug-specific T-cell responses in patients with anti-tuberculosis drug (ATD)-induced cutaneous hypersensitivity and its underlying mechanism. Methods We enrolled eight patients with ATD-induced maculopapular exanthema and DRESS and performed a lymphocyte transformation test. Subsequently, drug-specific T-cell clones were generated from four of the patients who showed proliferation in response to ATDs. We measured the drug-specific proliferative responses and counted the drug-specific interferon (IFN)-gamma/granzyme B-producing cells after drug stimulation. Antihuman leukocyte antigen (HLA) class I and class II blocking antibodies were used to analyse human leukocyte antigenrestricted T-cell responses. Results Positive proliferative responses to ATDs were mostly found in patients with cutaneous hypersensitivity. Furthermore, we isolated isoniazid/rifampicin-specific T cells from patients, which consisted primarily of CD4+ T cells. Drug-specific CD4+ T cells proliferated and secreted IFN-gamma/granzyme B when stimulated with isoniazid or rifampicin, respectively. Isoniazid-responsive T-cell clones did not proliferate in the presence of rifampicin and vice versa. Drug-specific T-cell responses were blocked in the presence of anti-HLA class II antibodies. Conclusions This study identifies the presence of isoniazid/rifampicin-specific T cells in patients with ATD-induced maculopapular exanthema and DRESS. Furthermore, it highlights the important role of drug-specific T-cell immune responses in the pathogenesis of these reactions. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | WILEY | - |
dc.subject | INDUCED LIVER-INJURY | - |
dc.subject | INDUCED HYPERSENSITIVITY SYNDROME | - |
dc.subject | HUMAN-LEUKOCYTE ANTIGEN | - |
dc.subject | ADVERSE-REACTIONS | - |
dc.subject | DRESS SYNDROME | - |
dc.subject | RISK-FACTORS | - |
dc.subject | HEPATOTOXICITY | - |
dc.subject | ASSOCIATION | - |
dc.subject | FLUCLOXACILLIN | - |
dc.subject | SEVERITY | - |
dc.title | Drug-specific CD4(+) T-cell immune responses are responsible for antituberculosis drug-induced maculopapular exanthema and drug reaction with eosinophilia and systemic symptoms syndrome | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Hur, G. -Y. | - |
dc.identifier.doi | 10.1111/bjd.14839 | - |
dc.identifier.scopusid | 2-s2.0-85007140935 | - |
dc.identifier.wosid | 000394755100034 | - |
dc.identifier.bibliographicCitation | BRITISH JOURNAL OF DERMATOLOGY, v.176, no.2, pp.378 - 386 | - |
dc.relation.isPartOf | BRITISH JOURNAL OF DERMATOLOGY | - |
dc.citation.title | BRITISH JOURNAL OF DERMATOLOGY | - |
dc.citation.volume | 176 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 378 | - |
dc.citation.endPage | 386 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Dermatology | - |
dc.relation.journalWebOfScienceCategory | Dermatology | - |
dc.subject.keywordPlus | INDUCED LIVER-INJURY | - |
dc.subject.keywordPlus | INDUCED HYPERSENSITIVITY SYNDROME | - |
dc.subject.keywordPlus | HUMAN-LEUKOCYTE ANTIGEN | - |
dc.subject.keywordPlus | ADVERSE-REACTIONS | - |
dc.subject.keywordPlus | DRESS SYNDROME | - |
dc.subject.keywordPlus | RISK-FACTORS | - |
dc.subject.keywordPlus | HEPATOTOXICITY | - |
dc.subject.keywordPlus | ASSOCIATION | - |
dc.subject.keywordPlus | FLUCLOXACILLIN | - |
dc.subject.keywordPlus | SEVERITY | - |
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