Correlation between serum granulysin level and clinical activity in patients with alopecia areata before and after tofacitinib therapy.
Alopecia areata
JAK inhibitors
biomarker
cytotoxicity
tofacitinib
treatment
Journal
Journal of cosmetic dermatology
ISSN: 1473-2165
Titre abrégé: J Cosmet Dermatol
Pays: England
ID NLM: 101130964
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
17
05
2020
revised:
11
06
2020
accepted:
26
06
2020
pubmed:
19
8
2020
medline:
15
5
2021
entrez:
19
8
2020
Statut:
ppublish
Résumé
Alopecia areata (AA) is a common immune-mediated disorder. Destruction of anagen hair follicles by cytotoxic T cells (CTL) plays a major role in the pathogenesis of AA. Serum granulysin has been shown to reflect overall activity of CTLs. In this study, we aimed to compare serum granulysin levels in patients with AA before and after therapy and to analyze correlation between serum granulysin levels and disease severity. We evaluated the Severity of Alopecia Tool (SALT) score and serum granuysin levels of 38 AA patients at baseline and at 6th month of therapy. Thirty-three patients were treated with tofacitinib 5 mg b.i.d, and five patients were treated with topical immunotherapy. Serum granulysin levels were measured by enzyme-linked immunosorbent assay. A moderate correlation was found between SALT scores and serum granulysin level at baseline (r = .378, P = .019). Baseline serum granulysin levels were significantly higher in patients with alopecia totalis/universalis compared with patients with patchy AA (P = .004, Z = 2.778). Serum granulysin levels significantly decreased in patients treated with tofacitinib compared to baseline (P = .001). The reduction in serum granulysin levels after tofacitinib therapy correlated with the reduction in SALT scores (P = .001). Our results suggest serum granulysin levels to be a good correlate of immunological activity of AA. We also assume granulysin to be a potential mediator of follicle attack, the effects of which is blocked by tofacitinib therapy. Therefore, changes in serum granulysin levels under therapy can reflect the downregulation of immunological activity of AA.
Sections du résumé
BACKGROUND
BACKGROUND
Alopecia areata (AA) is a common immune-mediated disorder. Destruction of anagen hair follicles by cytotoxic T cells (CTL) plays a major role in the pathogenesis of AA. Serum granulysin has been shown to reflect overall activity of CTLs.
AIMS
OBJECTIVE
In this study, we aimed to compare serum granulysin levels in patients with AA before and after therapy and to analyze correlation between serum granulysin levels and disease severity.
METHODS
METHODS
We evaluated the Severity of Alopecia Tool (SALT) score and serum granuysin levels of 38 AA patients at baseline and at 6th month of therapy. Thirty-three patients were treated with tofacitinib 5 mg b.i.d, and five patients were treated with topical immunotherapy. Serum granulysin levels were measured by enzyme-linked immunosorbent assay.
RESULTS
RESULTS
A moderate correlation was found between SALT scores and serum granulysin level at baseline (r = .378, P = .019). Baseline serum granulysin levels were significantly higher in patients with alopecia totalis/universalis compared with patients with patchy AA (P = .004, Z = 2.778). Serum granulysin levels significantly decreased in patients treated with tofacitinib compared to baseline (P = .001). The reduction in serum granulysin levels after tofacitinib therapy correlated with the reduction in SALT scores (P = .001).
CONCLUSIONS
CONCLUSIONS
Our results suggest serum granulysin levels to be a good correlate of immunological activity of AA. We also assume granulysin to be a potential mediator of follicle attack, the effects of which is blocked by tofacitinib therapy. Therefore, changes in serum granulysin levels under therapy can reflect the downregulation of immunological activity of AA.
Substances chimiques
Piperidines
0
Pyrimidines
0
Pyrroles
0
tofacitinib
87LA6FU830
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
971-975Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
Pratt CH, King LE, Messenger AG, Christiano AM, Sundberg JP. Alopecia areata. Nat Rev Dis Prim. 2017;16(3):17011.
Bodemer C, Peuchmaur M, Fraitaig S, Chatenoud L, Brousse N, De Prost Y. Role of cytotoxic T cells in chronic alopecia areata. J Invest Dermatol. 2000;114(1):112-116.
Ito T. Hair follicle is a target of stress hormone and autoimmune reactions. J Dermatol Sci. 2010;60(2):67-73.
Guo H, Cheng Y, Shapiro J, McElwee K. The role of lymphocytes in the development and treatment of alopecia areata. Expert Rev Clin Immunol. 2015;11(12):1335-1351.
Freyschmidt-Paul P, McElwee KJ, Botchkarev V, et al. Fas-deficient C3.MRL-Tnfrsf6lpr mice and Fas ligand-deficient C3H/HeJ-Tnfsf6gld mice are relatively resistant to the induction of alopecia areata by grafting of alopecia areata-affected skin from C3H/HeJ mice. J Investig Dermatology Symp Proc. 2003;8(1):104-108.
Ogawa K, Takamori Y, Suzuki K, et al. Granulysin in human serum as a marker of cell-mediated immunity. Eur J Immunol. 2003;33(7):1925-1933.
Ono S, Otsuka A, Yamamoto Y, et al. Serum granulysin as a possible key marker of the activity of alopecia areata. J Dermatol Sci. 2014;73(1):74-79.
Tojo G, Fujimura T, Kawano M, et al. Comparison of interleukin-17- producing cells in different clinical types of alopecia areata. Dermatology. 2013;227(1):78-82.
Liu LY, Craiglow BG, Dai F, King BA. Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients. J Am Acad Dermatol. 2017;76(1):22-28.
Xing L, Dai Z, Jabbari A, et al. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med. 2014;20(9):1043-1049.
Olsen EA, Hordinsky MK, Price VH, et al. Alopecia areata investigational assessment guidelines-Part II. National Alopecia Areata Foundation. J Am Acad Dermatol. 2004;51(3):440-447.
Jabbari A, Cerise JE, Chen JC, et al. Molecular signatures define alopecia areata subtypes and transcriptional biomarkers. EBioMedicine. 2016;1(7):240-247.
Phan K, Sebaratnam DF. JAK inhibitors for alopecia areata: a systematic review and meta-analysis. J Eur Acad Dermatology Venereol. 2019;33(5):850-856.
Jabbari A, Nguyen N, Cerise JE, et al. Treatment of an alopecia areata patient with tofacitinib results in regrowth of hair and changes in serum and skin biomarkers. Exp Dermatol. 2016;25(8):642-643.
Hogg AE, Bowick GC, Herzog NK, Cloyd MW, Endsley JJ. Induction of granulysin in CD8 + T cells by IL-21 and IL-15 is suppressed by human immunodeficiency virus-1. J Leukoc Biol. 2009;86(5):1191-1203.
Hoffmann R, Wenzel E, Huth A, et al. Cytokine mRNA levels in alopecia areata before and after treatment with the contact allergen diphenylcyclopropenone. J Invest Dermatol. 1994;103(4):530-533.
Simonetti O, Lucarini G, Bernardini ML, Simoncini C, Biagini G, Offidani A. Expression of vascular endothelial growth factor, apoptosis inhibitors (survivin and p16) and CCL27 in alopecia areata before and after diphencyprone treatment: an immunohistochemical study. Br J Dermatol. 2004;150(5):940-948.
Wasyłyszyn T, Kozłowski W, Zabielski SL. Changes in distribution pattern of CD8 lymphocytes in the scalp in alopecia areata during treatment with diphencyprone. Arch Dermatol Res. 2007;299(5-6):231-237.