title: Biomarkers of alopecia areata disease activity and response to corticosteroid treatment.
abstract: Alopecia areata (AA) is a common inflammatory disease targeting the anagen-stage hair follicle. Different cytokines have been implicated in the disease profile, but their pathogenic role is not yet fully determined. We studied biopsies of pretreatment lesional and non-lesional (NL) scalp and post-treatment (intra-lesional steroid injection) lesional scalp of 6 patchy patients with AA using immunohistochemistry and gene expression analysis. Immunohistochemistry showed increases in CD3(+) , CD8(+) T cells, CD11c(+) dendritic cells and CD1a(+) Langerhans cells within and around hair follicles of pretreatment lesional scalp, which decreased upon treatment. qRT-PCR showed in pretreatment lesional scalp (compared to NL) significant increases (P < 0.05) in expression of inflammatory markers (IL-2, IL-2RA, JAK3, IL-15), Th1 (CXCL10 and CXCL9), Th2 (IL-13, CCL17 and CCL18), IL-12/IL-23p40 and IL-32. Among these, we observed significant downregulation with treatment in IL-12/IL-23p40, CCL18 and IL-32. We also observed significant downregulation of several hair keratins in lesional scalp, with significant upregulation of KRT35, KRT75 and KRT86 in post-treatment lesional scalp. This study shows concurrent activation of Th1 and Th2 immune axes as well as IL-23 and IL-32 cytokine pathways in lesional AA scalp and defined a series of response biomarkers to corticosteroid injection. Clinical trials with selective antagonists coupled with cytokine-pathway biomarkers will be necessary to further dissect pathogenic immunity.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gulati
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Bonifacio
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.
authors.forename: Norma
authors.initials: N
authors.lastname: Kunjravia
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.
authors.forename: Xiuzhong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.|Dermatology Department, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Genetics and Genomics Science, Icahn Institute for Genomics and Multiscale Biology, New York, NY, USA.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Department of Dermatology, Tel-Hashomer Hospital, Tel Aviv, Israel.
authors.forename: Avner
authors.initials: A
authors.lastname: Shemer
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.|Dermatology Department, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Genetics and Genomics Science, Icahn Institute for Genomics and Multiscale Biology, New York, NY, USA.|Department of the Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000506:Alopecia Areata / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism*; D001706:Biopsy; D016207:Cytokines / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D007378:Interleukins / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D007801:Langerhans Cells / Q000378:metabolism; D008297:Male; D012535:Scalp / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D016207:Cytokines; C496971:IL32 protein, human; D007378:Interleukins; D007633:Keratins
keywords: alopecia areata; biomarkers; hair keratins; inflammatory cytokines