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Drug-specific CD4(+) T-cell immune responses are responsible for antituberculosis drug-induced maculopapular exanthema and drug reaction with eosinophilia and systemic symptoms syndrome

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dc.contributor.authorYe, YM-
dc.contributor.authorHur, GY-
dc.contributor.authorKim, SH-
dc.contributor.authorBan, GY-
dc.contributor.authorJee, YK-
dc.contributor.authorNaisbitt, DJ-
dc.contributor.authorPark, HS-
dc.contributor.authorKim, SH-
dc.date.accessioned2018-07-27T00:52:09Z-
dc.date.available2018-07-27T00:52:09Z-
dc.date.issued2017-
dc.identifier.issn0007-0963-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/15581-
dc.description.abstractBACKGROUND: 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 antituberculosis 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 antigen-restricted 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.
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dc.language.isoen-
dc.subject.MESHAdult-
dc.subject.MESHAntitubercular Agents-
dc.subject.MESHCD4-Positive T-Lymphocytes-
dc.subject.MESHDrug Hypersensitivity Syndrome-
dc.subject.MESHExanthema-
dc.subject.MESHFemale-
dc.subject.MESHHLA Antigens-
dc.subject.MESHHumans-
dc.subject.MESHImmunity, Cellular-
dc.subject.MESHIsoniazid-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHRifampin-
dc.titleDrug-specific CD4(+) T-cell immune responses are responsible for antituberculosis drug-induced maculopapular exanthema and drug reaction with eosinophilia and systemic symptoms syndrome-
dc.typeArticle-
dc.identifier.pmid27373553-
dc.contributor.affiliatedAuthor예, 영민-
dc.contributor.affiliatedAuthor반, 가영-
dc.contributor.affiliatedAuthor박, 해심-
dc.contributor.affiliatedAuthor김, 승현-
dc.type.localJournal Papers-
dc.identifier.doi10.1111/bjd.14839-
dc.citation.titleThe British journal of dermatology-
dc.citation.volume176-
dc.citation.number2-
dc.citation.date2017-
dc.citation.startPage378-
dc.citation.endPage386-
dc.identifier.bibliographicCitationThe British journal of dermatology, 176(2). : 378-386, 2017-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn1365-2133-
dc.relation.journalidJ000070963-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Journal Papers > Hospital > Clinical Trial Center
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