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Most patients with DRESS recover within a few weeks; however, some patients may suffer from a prolonged disease course and develop autoimmune sequelae.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To investigate the immune mechanism and therapeutic targets of patients with recalcitrant DRESS with a prolonged disease course.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Thirty-two patients with recalcitrant DRESS with a prolonged treatment course (\u2265 8 weeks; \u2018prolonged DRESS\u2019), 28 patients with DRESS with a short treatment course (&amp;lt; 2 weeks; \u2018short-duration DRESS\u2019) and 26 healthy donors (HDs) were enrolled.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Bulk transcriptome results showed that the mRNA expression levels of CCR8 and CXCR3 were significantly increased in blood samples from patients in the acute stage of prolonged DRESS [Padj = 1.50 \u00d7 10\u20139 (CCR8) and Padj = 2.60 \u00d7 10\u20134 (CXCR3), patients with prolonged DRESS compared with the HD group]. Serum and skin lesion concentrations of CCL1 and CXCL10 (ligands of CCR8 and CXCR3, respectively) were significantly increased in patients with prolonged DRESS compared with patients with short-duration DRESS. The results from high-parameter flow cytometry and autoantibody screening also identified significant increases in CD8+ GNLY+ CXCR3+ effector memory T cells, CD8+ central memory T cells, CD4+ CCR8+ T helper 2 cells and IgG anti-HES-6 autoantibodies in patients with prolonged DRESS. Furthermore, in vitro blocking assays revealed that Janus kinase inhibitors (JAKi; mainly tofacitinib and upadacitinib) significantly decreased the release of CCL1 and CXCL10. Some patients with prolonged DRESS were successfully treated with JAKi.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>JAKi (tofacitinib and upadacitinib) were associated with decreased concentrations of CCL1 and CXCL10, suggesting that they may attenuate CCR8\/CCL1 and CXCR3\/CXCL10 axis-mediated memory T-cell activation, which contributes to disease pathogenesis in patients with recalcitrant DRESS and a long-term treatment course.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n               <\/jats:sec>","DOI":"10.1093\/bjd\/ljae375","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T11:16:33Z","timestamp":1730891793000},"page":"293-305","source":"Crossref","is-referenced-by-count":14,"title":["CCR8\/CCL1 and CXCR3\/CXCL10 axis-mediated memory T-cell activation in patients with recalcitrant drug-induced hypersensitivity"],"prefix":"10.1093","volume":"192","author":[{"given":"Tsu-Man","family":"Chiu","sequence":"first","affiliation":[{"name":"Department of Dermatology, Chung Shan Medical University Hospital , Taichung ,","place":["Taiwan"]},{"name":"Institute of Medicine, Chung Shan Medical University , Taichung ,","place":["Taiwan"]},{"name":"School of Medicine, Chung Shan Medical University , Taichung ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7378-4235","authenticated-orcid":false,"given":"Chun-Bing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital , Linkou, Taipei, Tucheng and Keelung ,","place":["Taiwan"]},{"name":"Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University , Taoyuan ,","place":["Taiwan"]},{"name":"Department of Dermatology, Xiamen Chang Gung Hospital , Xiamen ,","place":["China"]},{"name":"College of Medicine, Chang Gung University , Taoyuan ,","place":["Taiwan"]},{"name":"Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital , Linkou ,","place":["Taiwan"]},{"name":"Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital , Keelung ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Wei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital , Linkou, Taipei, Tucheng and Keelung ,","place":["Taiwan"]},{"name":"Department of Dermatology, Xiamen Chang Gung Hospital , Xiamen ,","place":["China"]},{"name":"College of Medicine, Chang Gung University , Taoyuan ,","place":["Taiwan"]},{"name":"Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital , 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