title: Association of CD8(+) T lymphocyte repertoire spreading with the severity of DRESS syndrome.
abstract: T-cell receptor (TCR)-mediated cross-recognition is a major mechanism in the pathogenesis of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. However, the characteristics of the TCR repertoire and the clinical significance of repertoire reformation throughout the course of DRESS are unknown. Here, we isolated CD4(+) and CD8(+) T-cells from peripheral blood of 8 DRESS patients at 10-day intervals and, sequenced CDR3-regions of the TCRB chain by high-throughput sequencing to analyze the dynamic reformation in the T-cell repertoire hierarchy. Compared with healthy donors, T-cell expanded in peripheral repertoires from DRESS patient. The extent of fluctuation of dominant CD8(+) T-cell clones, but not of CD4(+) counterparts, correlated positively with the clinical severity and helped classify the enrolled subjects into "fluctuant" and "flat" repertoire groups. The anti-herpesvirus response, which was measured using anti-EBV/HHV antibodies, and the proportion of the homologous CD8(+) EBV-specific clonotypes, in the "fluctuant" group was substantial higher than that in the "flat" group. Furthermore, autoimmune sequelae were observed in a cured "fluctuant" patient. Collectively, the clinical relevance of the fluctuant CD8(+) T-cell repertoires supports the notion that herpes virus-mediated continuously de novo priming of newly pathogenic CD8(+) T-cell clones is an alternate mechanism responsible for the pathogenicity of DRESS.
authors.affiliation: Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Niu
authors.affiliation: 1] Biomedical Analysis Center, Third Military Medical University, Chongqing, China [2] Chongqing Key Laboratory of Cytomics, Chongqing, China.
authors.forename: Qingzhu
authors.initials: Q
authors.lastname: Jia
authors.affiliation: 1] Biomedical Analysis Center, Third Military Medical University, Chongqing, China [2] Chongqing Key Laboratory of Cytomics, Chongqing, China.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Ni
authors.affiliation: 1] Biomedical Analysis Center, Third Military Medical University, Chongqing, China [2] Chongqing Key Laboratory of Cytomics, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 1] Biomedical Analysis Center, Third Military Medical University, Chongqing, China [2] Chongqing Key Laboratory of Cytomics, Chongqing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xichuan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Zhai
authors.affiliation: 1] Biomedical Analysis Center, Third Military Medical University, Chongqing, China [2] Chongqing Key Laboratory of Cytomics, Chongqing, China.
authors.forename: Haili
authors.initials: H
authors.lastname: Yu
authors.affiliation: 1] Biomedical Analysis Center, Third Military Medical University, Chongqing, China [2] Chongqing Key Laboratory of Cytomics, Chongqing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Guan
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Regina
authors.initials: R
authors.lastname: Lin
authors.affiliation: Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Song
authors.affiliation: 1] Chongqing Key Laboratory of Cytomics, Chongqing, China [2] Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Qi-Jing
authors.initials: QJ
authors.lastname: Li
authors.affiliation: Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Hao
authors.affiliation: Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhong
authors.affiliation: 1] Biomedical Analysis Center, Third Military Medical University, Chongqing, China [2] Chongqing Key Laboratory of Cytomics, Chongqing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016000:Cluster Analysis; D063926:Drug Hypersensitivity Syndrome / Q000276:immunology / Q000473:pathology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D011948:Receptors, Antigen, T-Cell