title: Interleukin-15 Is Associated with Severity and Mortality in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.
abstract: Early diagnosis and prognosis monitoring for Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN) still remain a challenge. This study aims to explore any cytokine/chemokine with prognostic potential in Stevens-Johnson syndrome/TEN. Through screening a panel of 28 serological factors, IL-6, IL-8, IL-15, tumor necrosis factor-α, and granulysin were upregulated in patients with Stevens-Johnson syndrome/TEN and selected for the further validation in total 155 patients with Stevens-Johnson syndrome/TEN, including 77 from Taiwan and 78 from the Registry of Severe Cutaneous Adverse Reactions. Among these factors evaluated, the levels of IL-15 (r = 0.401; P < 0.001) and granulysin (r = 0.223; P = 0.026) were significantly correlated with the disease severity in 112 samples after excluding patients with insufficient data to calculate the score of TEN. In addition, IL-15 was also associated with mortality (P = 0.002; odds ratio, 1.09; 95% confidence interval, 1.03-1.14; P = 0.001; adjusted odds ratio, 1.10; 95% confidence interval, 1.04-1.16). Consistent results were obtained after the exclusion of Taiwanese patients with sepsis to rule out possible confounders. Moreover, IL-15 was shown to enhance cytotoxicity of cultured natural killer cells and blister cells from patients with TEN. Our findings highlight a usefulness of IL-15 in prognosis monitoring and therapeutic intervention of this devastating condition.
authors.affiliation: Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan; Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Linkou and Keelung, Taiwan.
authors.forename: Shih-Chi
authors.initials: SC
authors.lastname: Su
authors.affiliation: Dokumentationszentrum schwerer Hautreaktionen, Department of Dermatology, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Maja
authors.initials: M
authors.lastname: Mockenhaupt
authors.affiliation: Department of Dermatology, Hospital Henri Mondor, Créteil, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Wolkenstein
authors.affiliation: Biostatistics and Epidemiology Unit, Gustave Roussy, Villejuif, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Dunant
authors.affiliation: University Medical Center Henri Mondor, ImmunoBiology Department and Inserm U955, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Le Gouvello
authors.affiliation: Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Linkou and Keelung, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chun-Bing
authors.initials: CB
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Hospital Henri Mondor, Créteil, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Chosidow
authors.affiliation: Department of Dermatology, Hospital Henri Mondor, Créteil, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Valeyrie-Allanore
authors.affiliation: Research Unit, Hospital La Paz Health Research Institute (IdiPAZ), Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Bellon
authors.affiliation: Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Peggy
authors.initials: P
authors.lastname: Sekula
authors.affiliation: Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Linkou and Keelung, Taiwan.
authors.forename: Chuang-Wei
authors.initials: CW
authors.lastname: Wang
authors.affiliation: Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schumacher
authors.affiliation: Department of Dermatology, Reference Center for Cutaneous Adverse Reactions, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Sylvia H
authors.initials: SH
authors.lastname: Kardaun
authors.affiliation: Institute of Pharmacology, School of Medicine, Infection and Immunity Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shuen-Iu
authors.initials: SI
authors.lastname: Hung
authors.affiliation: Department of Dermatology, Hospital Henri Mondor, Créteil, France. Electronic address: jean-claude.roujeau@wanadoo.fr.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Roujeau
authors.affiliation: Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan; Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Linkou and Keelung, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China. Electronic address: chung1@cgmh.org.tw.
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Chung
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018925:Chemokines / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D019409:Interleukin-15 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012042:Registries; D012720:Severity of Illness Index; D013262:Stevens-Johnson Syndrome / Q000097:blood / Q000401:mortality / Q000503:physiopathology*; D013624:Taiwan; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D018925:Chemokines; D016207:Cytokines; D019409:Interleukin-15