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. 2023 Nov;143(11):2275-2282.e6.
doi: 10.1016/j.jid.2023.03.1689. Epub 2023 Jul 20.

Lesional CD8+ T-Cell Number Predicts Surgical Outcomes of Melanocyte-Keratinocyte Transplantation Surgery for Vitiligo

Maggi A Refat  1 , James P Strassner  2 , Michael L Frisoli  2 , Mehdi Rashighi  2 , Jillian Richmond  2 , Essam Nada  3 , Ramadan Saleh  3 , Mohammed Abu El-Hamd  3 , Dori Goldberg  2 , Bassel H Mahmoud  2 , John E Harris  4
Affiliations

Lesional CD8+ T-Cell Number Predicts Surgical Outcomes of Melanocyte-Keratinocyte Transplantation Surgery for Vitiligo

Maggi A Refat et al. J Invest Dermatol. 2023 Nov.

Abstract

The melanocyte-keratinocyte transplantation procedure (MKTP) treats stable and recalcitrant vitiligo. Despite careful selection of candidates based on clinical stability, the success of the procedure is unpredictable. The aim of our study was to define the immunological profile of stable vitiligo lesions undergoing MKTP and correlate them with clinical outcomes. We included 20 MKTP candidates with vitiligo and a patient with piebaldism as a control. Prior to MKTP, T-cell subsets and chemokines in the recipient skin were measured by flow cytometry and ELISA. During MKTP, melanocytes in the donor skin were quantified by flow cytometry. After MKTP, patients were followed for 12 months and repigmentation was assessed clinically and by ImageJ analysis of clinical photographs. Baseline immunologic biomarkers, duration of clinical stability, and transplanted melanocyte number were correlated to postsurgical repigmentation scores. CD8+ T cells were elevated in 43% of the clinically stable vitiligo lesions. CD8+ T-cell number negatively correlated with postsurgical repigmentation scores (r = -0.635, P = 0.002). Duration of clinical stability, skin chemokines, and transplanted melanocyte number did not influence postsurgical repigmentation. This study demonstrates that CD8+ T-cell number correlates negatively with success of postsurgical repigmentation and can be a biomarker to identify ideal surgical candidates.

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Conflict of interest statement

CONFLICT OF INTEREST

JMR and JEH are inventors on patent application number 62489191, “Diagnosis and Treatment of Vitiligo,” which covers targeting IL-15 and resident memory T cell for the treatment of vitiligo. JEH is a scientific founder of Villaris Therapeutics, which is focused on developing treatments for vitiligo. JMR and JEH are inventors on patent application number 15/851,651, “Anti-human CXCR3 antibodies for the Treatment of Vitiligo,” which covers targeting CXCR3 for the treatment of vitiligo. JEH has served as a consultant and/or investigator for 3rd Rock Ventures, AbbVie, Aclaris Therapeutics, Admirx, Aldena, Almirall, AnaptysBio, Avita, BiologicsMD, Boston Pharma, Bridge-Bio, Celgene, Cogen Therapeutics, Dermavant, Dermira, EMD Serono, Frazier Management, Genzyme/Sanofi, Granular Therapeutics, Incyte, Janssen, LEO Pharma, Methuselah Health, NIRA Biosciences, Pandion, Pfizer, Platelet Biogenesis, Rheos Medicines, Sonoma Biotherapeutics, Stiefel/GSK, Sun Pharmaceuticals, Temprian Therapeutics, TeVido BioDevices, The Expert Institute, Twi Biotech, Villaris Therapeutics, Vimela, Matchpoint Therapeutics, and Merck. JEH reports equity in TeVido Biodevices, Rheos, Villaris Therapeutics, NIRA Biosciences, Aldena, Vimela, and Incyte. JEH is a founder of Villaris Therapeutics, NIRA Biosciences, Aldena, and Vimela. Villaris was recently acquired by Incyte. The remaining authors state no conflict of interest.

Figures

Figure 1.
Figure 1.. CXCL9 and CXCL10 chemokines and CD8+ T cells in MKTP candidate lesions compared with those in nonlesional and healthy skin.
Red lines represent predefined cutoff values above which (a) CXCL9, (b) CXCL10, or (c) T-cell number define disease activity. MKTP, melanocyte–keratinocyte transplantation procedure; ns, nonsignificant.
Figure 2.
Figure 2.. Relationship between duration of lesional stability, lesional CD8+ T-cell number, and transplanted suspension melanocyte number with the percentage of postsurgical acquired repigmentation.
Scatter plots with fitted regression lines using Spearman correlation coefficient indicating (a) lack of correlation between duration of lesional stability and score of repigmentation as well as (b) CD8+ T-cell number in the treated lesion. (c) No significant correlation was noted between the number of transplanted melanocytes and the score of repigmentation. (d) Significant negative correlation between CD8+ T cells in the lesion and score of repigmentation.
Figure 3.
Figure 3.. CD8+ T-cell infiltrate reflects surgical outcome.
Excellent surgical repigmentation, by Wood’s lamp, in a (a) patient with piebaldism and (b) patient with vitiligo with low lesional baseline CD8+ T-cell count by flow cytometry and immunofluorescent histochemistry. Poor surgical repigmentation in (c) a patient with vitiligo with high lesional baseline CD8+ T-cell count by flow cytometry and immunofluorescent histochemistry. Subjects consented to the publication of the image.
Figure 4.
Figure 4.. Relapse of vitiligo after successful MKTP despite clinical stability with high baseline lesional CD8+ T-cell count.
Nonsegmental vitiligo lesions in a woman aged 41 years (top left panel) and a man aged 57 years show 50 and 90% repigmentation, respectively, at 4 months (bottom left panel) and then a relapse of depigmentation 10 months after the procedure. Both patients had high baseline lesional CD8+ T-cell number (middle panel) and relapsing course (right panel). F/U, follow-up; MKTP, melanocyte–keratinocyte transplantation procedure.
Figure 5.
Figure 5.. MKTP technique.
(a–c) Left panel: Obtaining a superficial split thickness shave biopsy from a healthy donor site from the patient. Middle panel: (d) Donor skin was processed by enzymatic digestion (0.25% trypsin and 0.02% EDTA) and mechanical separation, (e) then centrifuged to form a pellet rich with melanocytes, resuspended into a single cell suspension, and (f) loaded into a syringe. (g) Right panel: The recipient skin was prepared by laser dermabrasion. (h) Finally, the suspension was applied to the denuded recipient skin and secured with multiple-layer dressings. MKTP, melanocyte–keratinocyte transplantation procedure.
See this image and copyright information in PMC

References

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