Tissue-resident Memory T Cells Expression Among the Repigmentation Patterns Induced by NB-UVB Phototherapy in Vitiligo

Vitiligo Clinical Trial

Official title:

Tissue-resident Memory T Cells Expression Among the Repigmentation Patterns Induced by NB-UVB Phototherapy in Vitiligo

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05506995
• Other study ID #: 63-21
• Status: Completed
• Start date: August 1, 2021
• Est. completion date: August 3, 2022

Study information

• Verified date: August 2022
• Source: Universidad Autonoma de San Luis Potosí
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Vitiligo is the most commonly acquired depigmentation disorder characterized by selective destruction of melanocytes resulting in well-circumscribed achromic macules. Tissue-resident memory T cells (TRM) are memory T lymphocyte subsets that reside in the skin, lack recirculation, proliferate locally, produce cytokines, and may be implicated in relapses. NB-UVB Phototherapy induces repigmentation in certain patterns. The aim of this study was to determine the levels of TRM cells on vitiligo lesions, and after phototherapy by repigmentation pattern.

Description:

Vitiligo is the most commonly acquired depigmentation disorder characterized by the selective destruction of melanocytes. Its etiology is not yet fully understood, but the most accepted hypotheses are genetic predisposition, environmental factors, oxidative stress and immune response. In relation with the latter, the damage-associated molecular patterns activate TRM cells and induce interferon-gamma that release CXCL9/10, recruiting cytotoxic CD8+ that ultimately destroys melanocytes. Furthermore, the lesions recur 40% in the first year and in the same site, suggesting local autoimmune response by TRM cells.

The TRM cells are memory T lymphocyte subsets that reside in the skin, lack recirculation, proliferate locally, and produce cytokines. TRM cells express the CD69+CD103+ surface markers. Moreover, TRM cells express specific transcription factors like Hobbit, Blimp1, Runx3 and Notch1, which regulate their differentiation and survival.

Interleukin (IL)-15 stimulates Hobbit, which drives TRM cells long-term maintenance by blocking CCR7-S1PR1 and promoting the expression of CD103+. Blimp1 is essential for the differentiation of TRM cells, as it inhibits the differentiation of naive T cells into circulating-memory T cells, and regulates the effector function by stimulating granzyme B and promoting the expression of CD69+. Runx3 is essential for TRM cells long-term maintenance by promoting CD103+, which can also induce Blimp1 and Hobbit. Notch1 is essential for the maintenance of CD103+, facilitating the TRM-epithelium linking. Both TRM cells and central-memory T cells have been found in vitiligo lesions, and the CD69+CD103+ TRM cells are increased in vitiligo skin.

NB-UVB phototherapy is the first line treatment for vitiligo involving more than 10 percent of the body surface area, with an average response rate of 67%. It promotes repigmentation by differentiation and migration of perilesional melanocytes, tyrosinase increase and inhibition of effector and memory T cells. NB-UVB promotes different patterns of repigmentation such as follicular, marginal, and diffuse. The NB-UVB exposure causes a decrease in the transforming factor beta that maintain the expression of CD103+, but there is no data about the CD69+ modification, suggesting a possible effect on TRM cells.

Vitiligo relapses tend to be at the same site of previous lesions, suggesting local autoimmunity by the TRM cells that could be modified by UVB-NB phototherapy. Phototherapy can inhibit effector and memory-T cells; however its effect on TRM cells in vitiligo and their modification is unknown. The purpose of this study was to determine the levels of TRM cells on vitiligo lesions, and following NB-UVB phototherapy by repigmentation pattern.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: August 3, 2022
• Est. primary completion date: July 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years of age or older

• Symmetric vitiligo

• Affected body surface greater than 10%

• Patients with follicular, marginal and diffuse repigmenting patterns

• No previous topical or systemic treatment in the previous 2 and 3 months, respectively

• Signed informed consent

Exclusion Criteria:

• Concomitant treatment or systemic diseases

• Pregnancy

• Drugs intake

• Mental disorders

• Acral, universal or segmental vitiligo

Related Conditions & MeSH terms

• Vitiligo

Locations

Country	Name	City	State
Mexico	Dermatology Department. Hospital Central "Dr. Ignacio Morones Prieto"	San Luis Potosí

Sponsors (1)

Lead Sponsor	Collaborator
Universidad Autonoma de San Luis Potosí

Country where clinical trial is conducted

Mexico, 

References & Publications (10)

Azzolino V, Zapata L Jr, Garg M, Gjoni M, Riding RL, Strassner JP, Richmond JM, Harris JE. Jak Inhibitors Reverse Vitiligo in Mice but Do Not Deplete Skin Resident Memory T Cells. J Invest Dermatol. 2021 Jan;141(1):182-184.e1. doi: 10.1016/j.jid.2020.04.0 — View Citation

Bae JM, Jung HM, Hong BY, Lee JH, Choi WJ, Lee JH, Kim GM. Phototherapy for Vitiligo: A Systematic Review and Meta-analysis. JAMA Dermatol. 2017 Jul 1;153(7):666-674. doi: 10.1001/jamadermatol.2017.0002. Review. — View Citation

Behr FM, Chuwonpad A, Stark R, van Gisbergen KPJM. Armed and Ready: Transcriptional Regulation of Tissue-Resident Memory CD8 T Cells. Front Immunol. 2018 Jul 30;9:1770. doi: 10.3389/fimmu.2018.01770. eCollection 2018. Review. — View Citation

Castanedo-Cázares JP, Cortés-García JD, Fuentes-Ahumada C, Martinez-Rosales K, Torres-Álvarez B. Repigmentation patterns induced by NB-UVB and their relationship with melanocytic migration and proliferation in vitiligo. Photodermatol Photoimmunol Photomed — View Citation

Fraczek A, Owczarczyk-Saczonek A, Placek W. The Role of T(RM) Cells in the Pathogenesis of Vitiligo-A Review of the Current State-Of-The-Art. Int J Mol Sci. 2020 May 18;21(10). pii: E3552. doi: 10.3390/ijms21103552. Review. — View Citation

Mackay LK, Minnich M, Kragten NA, Liao Y, Nota B, Seillet C, Zaid A, Man K, Preston S, Freestone D, Braun A, Wynne-Jones E, Behr FM, Stark R, Pellicci DG, Godfrey DI, Belz GT, Pellegrini M, Gebhardt T, Busslinger M, Shi W, Carbone FR, van Lier RA, Kallies — View Citation

Patra V, Laoubi L, Nicolas JF, Vocanson M, Wolf P. A Perspective on the Interplay of Ultraviolet-Radiation, Skin Microbiome and Skin Resident Memory TCRaß+ Cells. Front Med (Lausanne). 2018 May 30;5:166. doi: 10.3389/fmed.2018.00166. eCollection 2018. — View Citation

Richmond JM, Strassner JP, Rashighi M, Agarwal P, Garg M, Essien KI, Pell LS, Harris JE. Resident Memory and Recirculating Memory T Cells Cooperate to Maintain Disease in a Mouse Model of Vitiligo. J Invest Dermatol. 2019 Apr;139(4):769-778. doi: 10.1016/ — View Citation

Riding RL, Harris JE. The Role of Memory CD8(+) T Cells in Vitiligo. J Immunol. 2019 Jul 1;203(1):11-19. doi: 10.4049/jimmunol.1900027. Review. — View Citation

Zubair R, Hamzavi IH. Phototherapy for Vitiligo. Dermatol Clin. 2020 Jan;38(1):55-62. doi: 10.1016/j.det.2019.08.005. Epub 2019 Oct 18. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tissue-resident memory T cells	To quantify the expression of Tissue-resident memory T cells before and after phototherapy	Up to 1 year
Secondary	Tissue-resident memory T cells among the repigmentation patterns	To quantify the expression of Tissue-resident memory T cells among the repigmentation patterns induced by NB-UVB phototherapy	Up to 1 year
Secondary	Arrangment of the Tissue-resident memory T cells among the repigmentation patterns	To show and quantify the fluorescence intensity of the CD69+CD103+ TRM cells among the repigmentation patterns induced by NB-UVB phototherapy	Up to 1 year
Secondary	TRM transcriptional factors profile	To quantify the TRM transcriptional factors expression in lesional skin and between the repigmentation patterns.	Up to 1 year