James P Strassner1, Mehdi Rashighi1, Maggi Ahmed Refat2, Jillian M Richmond1, John E Harris3. 1. Department of Medicine, Division of Dermatology, University of Massachusetts Medical School, Worcester, Massachusetts. 2. Department of Medicine, Division of Dermatology, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Dermatology, Sohag University, Sohag, Egypt. 3. Department of Medicine, Division of Dermatology, University of Massachusetts Medical School, Worcester, Massachusetts. Electronic address: john.harris@umassmed.edu.
Abstract
BACKGROUND: Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies. OBJECTIVE: To investigate potential biomarkers of disease activity directly in the skin of vitiligo subjects and healthy subjects. METHODS: Patient skin was sampled via a modified suction-blister technique, allowing for minimally invasive, objective assessment of cytokines and T-cell infiltrates in the interstitial skin fluid. Potential biomarkers were first defined and later validated in separate study groups. RESULTS: In screening and validation, CD8+ T-cell number and C-X-C motif chemokine ligand (CXCL) 9 protein concentration were significantly elevated in active lesional compared to nonlesional skin. CXCL9 protein concentration achieved greater sensitivity and specificity by receiver operating characteristic analysis. Suction blistering also allowed for phenotyping of the T-cell infiltrate, which overwhelmingly expresses C-X-C motif chemokine receptor 3. LIMITATIONS: A small number of patients were enrolled for the study, and only a single patient was used to define the treatment response. CONCLUSION: Measuring CXCL9 directly in the skin might be effective in clinical trials as an early marker of treatment response. Additionally, use of the modified suction-blister technique supports investigation of inflammatory skin diseases using powerful tools like flow cytometry and protein quantification.
BACKGROUND:Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies. OBJECTIVE: To investigate potential biomarkers of disease activity directly in the skin of vitiligo subjects and healthy subjects. METHODS:Patient skin was sampled via a modified suction-blister technique, allowing for minimally invasive, objective assessment of cytokines and T-cell infiltrates in the interstitial skin fluid. Potential biomarkers were first defined and later validated in separate study groups. RESULTS: In screening and validation, CD8+ T-cell number and C-X-C motif chemokine ligand (CXCL) 9 protein concentration were significantly elevated in active lesional compared to nonlesional skin. CXCL9 protein concentration achieved greater sensitivity and specificity by receiver operating characteristic analysis. Suction blistering also allowed for phenotyping of the T-cell infiltrate, which overwhelmingly expresses C-X-C motif chemokine receptor 3. LIMITATIONS: A small number of patients were enrolled for the study, and only a single patient was used to define the treatment response. CONCLUSION: Measuring CXCL9 directly in the skin might be effective in clinical trials as an early marker of treatment response. Additionally, use of the modified suction-blister technique supports investigation of inflammatory skin diseases using powerful tools like flow cytometry and protein quantification.
Authors: Jillian M Richmond; Dinesh S Bangari; Kingsley I Essien; Sharif D Currimbhoy; Joanna R Groom; Amit G Pandya; Michele E Youd; Andrew D Luster; John E Harris Journal: J Invest Dermatol Date: 2016-09-26 Impact factor: 8.551
Authors: Tag Anbar; Nehal Mohamed Zuel-Fakkar; Mary Fikry Matta; Mai Mohammed Ibrahim Arbab Journal: Eur J Dermatol Date: 2016 Jan-Feb Impact factor: 3.328
Authors: Kyle J Gellatly; James P Strassner; Kingsley Essien; Maggi Ahmed Refat; Rachel L Murphy; Anthony Coffin-Schmitt; Amit G Pandya; Andrea Tovar-Garza; Michael L Frisoli; Xueli Fan; Xiaolan Ding; Evangeline E Kim; Zainab Abbas; Patrick McDonel; Manuel Garber; John E Harris Journal: Sci Transl Med Date: 2021-09-08 Impact factor: 17.956
Authors: Jillian M Richmond; James P Strassner; Lucio Zapata; Madhuri Garg; Rebecca L Riding; Maggi A Refat; Xueli Fan; Vincent Azzolino; Andrea Tovar-Garza; Naoya Tsurushita; Amit G Pandya; J Yun Tso; John E Harris Journal: Sci Transl Med Date: 2018-07-18 Impact factor: 17.956