{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:03:55Z","timestamp":1793034235859,"version":"4.5.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Vitiligo is an acquired depigmentation skin disease caused by immune-mediated death of melanocytes. The most common treatment for vitiligo is narrow band ultraviolet B phototherapy, which often is combined with topical therapies such as tacrolimus. However, patients\u2019 responses to these treatments show large variations. To date, the mechanism for this heterogeneity is unknown, and there are no molecular indicators that can predict an individual patient\u2019s response to therapy. The goal of this study is to identify clinical parameters and gene expression biomarkers associated with vitiligo response to therapy. Six patients with segmental vitiligo and 30 patients with non-segmental vitiligo underwent transcriptome sequencing of lesional and nonlesional skin at baseline before receiving combined UBUVB and tacrolimus therapy for 6 month, and were separated into good response and bad response groups based on target lesion achieving &amp;gt; 10% repigmentation or not. Our study revealed that treatment-responsive vitiligo lesions had significantly shorter disease duration compared with non-responsive vitiligo lesions (2.5 years vs 11.5 years, p=0.046, t-Test), while showing no significant differences in the age, gender, ethnicity, vitiligo subtype, or disease severity. Transcriptomic analyses identified a panel of 68 genes separating the good response from bad response lesions including upregulation of immune active genes, such as CXCL10, FCRL3, and TCR, Further, compared with vitiligo lesions with long disease duration, the lesions with short duration also have much higher level of expression of immune-active genes, including some (such as FCRL3 and TCR genes) that are associated with favorable therapeutic response. In conclusion, our study has identified clinical parameters such as short disease duration and a panel of immune active and other gene expression biomarkers that are associated with favorable response to immune suppressive NBUVB + tacrolimus therapy. These markers may be useful clinically for individualized therapeutic management of vitiligo patients in the future.<\/jats:p>","DOI":"10.3389\/fimmu.2021.613031","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T14:28:26Z","timestamp":1614954506000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Vitiligo Skin Biomarkers Associated With Favorable Therapeutic Response"],"prefix":"10.3389","volume":"12","author":[{"given":"Qianli","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingwan","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gigi","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey","family":"Lui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingyu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youwen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2010.11.061","article-title":"Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up","volume":"65","author":"Alikhan","year":"2011","journal-title":"J\u00a0Am Acad Dermatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.144.8.1062","article-title":"Characteristics of patients with universal vitiligo and health-related quality of life","volume":"144","author":"Linthorst Homan","year":"2008","journal-title":"Arch Dermatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2009.03.022","article-title":"The burden of vitiligo: patient characteristics associated with quality of life","volume":"61","author":"Linthorst Homan","year":"2009","journal-title":"J Am Acad Dermatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2001.tb00004.x","article-title":"Psychiatric morbidity in vitiligo and psoriasis: a comparative study from India","volume":"28","author":"Mattoo","year":"2001","journal-title":"J Dermatol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1468-3083.2005.01369.x","article-title":"Psychosocial effects of vitiligo","volume":"20","author":"Ongenae","year":"2006","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.jaad.2015.08.063","article-title":"Comorbid autoimmune diseases in patients with vitiligo: A cross-sectional study","volume":"74","author":"Gill","year":"2016","journal-title":"J Am Acad Dermatol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1159\/000354607","article-title":"Comorbidities associated with vitiligo: a ten-year retrospective study","volume":"227","author":"Sheth","year":"2013","journal-title":"Dermatology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.gene.2018.01.053","article-title":"Fine-mapping analysis of the MHC region for vitiligo based on a new Han-MHC reference panel","volume":"648","author":"Yang","year":"2018","journal-title":"Gene"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.320","article-title":"Association analyses identify three susceptibility Loci for vitiligo in the Chinese Han population","volume":"133","author":"Tang","year":"2013","journal-title":"J Invest Dermatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/ng.603","article-title":"Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC","volume":"42","author":"Quan","year":"2010","journal-title":"Nat Genet"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-0820","article-title":"Platelet-derived growth factor receptor alpha gene mutations in vitiligo vulgaris","volume":"90","author":"Xu","year":"2010","journal-title":"Acta Derm Venereol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.06.004","article-title":"The Genetic Basis of Vitiligo","volume":"141","author":"Spritz","year":"2020","journal-title":"J Invest Dermatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908547","article-title":"Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo","volume":"362","author":"Jin","year":"2010","journal-title":"N Engl J Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061592","article-title":"NALP1 in vitiligo-associated multiple autoimmune disease","volume":"356","author":"Jin","year":"2007","journal-title":"N Engl J Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0227909","article-title":"The relationship between stress and vitiligo: Evaluating perceived stress and electronic medical record data","volume":"15","author":"Henning","year":"2020","journal-title":"PloS One"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12183","article-title":"A central role for inducible heat-shock protein 70 in autoimmune vitiligo","volume":"22","author":"Mosenson","year":"2013","journal-title":"Exp Dermatol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"223ra23","DOI":"10.1126\/scitranslmed.3007811","article-title":"CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo","volume":"6","author":"Rashighi","year":"2014","journal-title":"Sci Transl Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051040","article-title":"Transcriptome analysis reveals markers of aberrantly activated innate immunity in vitiligo lesional and non-lesional skin","volume":"7","author":"Yu","year":"2012","journal-title":"PloS One"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2016.11.006","article-title":"Chemical-Induced Vitiligo","volume":"35","author":"Harris","year":"2017","journal-title":"Dermatol Clin"},{"key":"B20","article-title":"Vitiliginous lesions induced by amyl nitrite exposure","volume":"91","author":"Vine","year":"2013","journal-title":"Cutis"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12162","article-title":"Provoking factors, including chemicals, in Dutch patients with vitiligo","volume":"168","author":"Vrijman","year":"2013","journal-title":"Br J Dermatol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/5416728","article-title":"Heme Oxygenases: Cellular Multifunctional and Protective Molecules against UV-Induced Oxidative Stress","volume":"2019","author":"Chen","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/2841814","article-title":"RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis","volume":"2019","author":"Sastry","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9613090","article-title":"Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases","volume":"2019","author":"Nandi","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12641","article-title":"Polymorphism of the E-cadherin gene CDH1 is associated with susceptibility to vitiligo","volume":"24","author":"Tarle","year":"2015","journal-title":"Exp Dermatol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"15011","DOI":"10.1038\/nrdp.2015.11","article-title":"Vitiligo","volume":"1","author":"Picardo","year":"2015","journal-title":"Nat Rev Dis Primers"},{"key":"B27","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1111\/j.1755-148X.2012.00997.x","article-title":"Revised classification\/nomenclature of vitiligo and related issues: the Vitiligo Global Issues Consensus Conference","volume":"25","author":"Ezzedine","year":"2012","journal-title":"Pigment Cell Melanoma Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000523","article-title":"Genetic variation of promoter sequence modulates XBP1 expression and genetic risk for vitiligo","volume":"5","author":"Ren","year":"2009","journal-title":"PloS Genet"},{"key":"B29","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.det.2019.08.005","article-title":"Phototherapy for Vitiligo","volume":"38","author":"Zubair","year":"2020","journal-title":"Dermatol Clin"},{"key":"B30","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1111\/pcmr.12561","article-title":"Repigmentation in vitiligo: position paper of the Vitiligo Global Issues Consensus Conference","volume":"30","author":"Gan","year":"2017","journal-title":"Pigment Cell Melanoma Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.140.6.677","article-title":"Parametric modeling of narrowband UV-B phototherapy for vitiligo using a novel quantitative tool: the Vitiligo Area Scoring Index","volume":"140","author":"Hamzavi","year":"2004","journal-title":"Arch Dermatol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09217.x","article-title":"Analysis of interleukin-10 levels in lesions of vitiligo following treatment with topical tacrolimus","volume":"161","author":"Taher","year":"2009","journal-title":"Br J Dermatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2002.126250","article-title":"Topical tacrolimus for repigmentation of vitiligo","volume":"47","author":"Grimes","year":"2002","journal-title":"J Am Acad Dermatol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/phpp.12593","article-title":"Efficacy of combination therapy of narrowband-ultraviolet B phototherapy or excimer laser with topical tacrolimus for vitiligo: An updated systematic review and meta-analysis","volume":"37","author":"Chang","year":"2021","journal-title":"Photodermatol Photoimmunol Photomed"},{"key":"B35","article-title":"Tacrolimus (FK506) ointment combined with Nb-UVB could activate both hair follicle (HF) and dermal melanocyte precursors in vitiligo: the first histopathological and clinical study","volume-title":"Arch Dermatol Res","author":"Gauthier","year":"2020"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/ajd.13096","article-title":"The efficacy and safety of tacrolimus as mono- and adjunctive therapy for vitiligo: A systematic review of randomised clinical trials","volume":"61","author":"Arora","year":"2020","journal-title":"Australas J Dermatol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4103\/0378-6323.113091","article-title":"Efficacy and tolerability of combined treatment with NB-UVB and topical tacrolimus versus NB-UVB alone in patients with vitiligo vulgaris: a randomized intra-individual open comparative trial","volume":"79","author":"Satyanarayan","year":"2013","journal-title":"Indian J Dermatol Venereol Leprol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2011.04002.x","article-title":"Treatment of vitiligo with narrowband-UVB (TL01) combined with tacrolimus ointment (0.1%) vs. placebo ointment, a randomized right\/left double-blind comparative study","volume":"25","author":"Nordal","year":"2011","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B39","first-page":"57","article-title":"Topical treatment and combination approaches for vitiligo: new insights, new developments","volume":"145","author":"Hossani-Madani","year":"2010","journal-title":"G Ital Dermatol Venereol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1080\/09546630802155057","article-title":"The efficacy of pimecrolimus 1% cream plus narrow-band ultraviolet B in the treatment of vitiligo: a double-blind, placebo-controlled clinical trial","volume":"20","author":"Esfandiarpour","year":"2009","journal-title":"J Dermatol Treat"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2006.02101.x","article-title":"Narrow-band UVB phototherapy combined with tacrolimus ointment in vitiligo: a review of 110 patients","volume":"21","author":"Fai","year":"2007","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.13271","article-title":"Photolichenoid papules within vitiligo induced by narrowband UVB phototherapy","volume":"30","author":"AlJasser","year":"2016","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2015.1520","article-title":"Tofacitinib Citrate for the Treatment of Vitiligo: A Pathogenesis-Directed Therapy","volume":"151","author":"Craiglow","year":"2015","journal-title":"JAMA Dermatol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.01.033","article-title":"Vitiligo: Targeted Therapies Add Color to Disease Pathophysiology","volume":"140","author":"Ezzedine","year":"2020","journal-title":"J Invest Dermatol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30609-7","article-title":"Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial","volume":"396","author":"Rosmarin","year":"2020","journal-title":"Lancet"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2018.02.023","article-title":"Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib: A 32-week open-label extension study with optional narrow-band ultraviolet B","volume":"78","author":"Joshipura","year":"2018","journal-title":"J Am Acad Dermatol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s13555-020-00431-6","article-title":"Dermoscopic and Clinical Response Predictor Factors in Nonsegmental Vitiligo Treated with Narrowband Ultraviolet B Phototherapy: A Prospective Observational Study","volume":"10","author":"Errichetti","year":"2020","journal-title":"Dermatol Ther (Heidelb)"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0781.2006.00222.x","article-title":"Evaluation of the effects of NB-UVB in both segmental and non-segmental vitiligo affecting different body sites","volume":"22","author":"Anbar","year":"2006","journal-title":"Photodermatol Photoimmunol Photomed"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp0804388","article-title":"Clinical practice. Vitiligo","volume":"360","author":"Taieb","year":"2009","journal-title":"N Engl J Med"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.133.12.1525","article-title":"Treatment of vitiligo with UV-B radiation vs topical psoralen plus UV-A","volume":"133","author":"Westerhof","year":"1997","journal-title":"Arch Dermatol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1016\/j.jaad.2020.03.122","article-title":"Technological advances for the detection of melanoma: Advances in molecular techniques","volume":"83","author":"Fried","year":"2020","journal-title":"J\u00a0Am Acad Dermatol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2019.03.1160","article-title":"Side-by-Side Comparison of Skin Biopsies and Skin Tape Stripping Highlights Abnormal Stratum Corneum in Atopic Dermatitis","volume":"139","author":"Kim","year":"2019","journal-title":"J Invest Dermatol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.jdermsci.2006.08.007","article-title":"Analysis of RNA recovery and gene expression in the epidermis using non-invasive tape stripping","volume":"44","author":"Wong","year":"2006","journal-title":"J\u00a0Dermatol Sci"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.613031\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T14:24:55Z","timestamp":1616077495000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.613031\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,5]]},"references-count":53,"alternative-id":["10.3389\/fimmu.2021.613031"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.613031","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,5]]},"article-number":"613031"}}