Clinical trial NCT05506995: Tissue-resident Memory T Cells Expression Among the Repigmentation Patterns Induced by NB-UVB Phototherapy in Vitiligo
Official title: Tissue-resident Memory T Cells Expression Among the Repigmentation Patterns Induced by NB-UVB Phototherapy in Vitiligo
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Vitiligo
Keywords: vitiligo
Ultraviolet Therapy
Pigmentation
Tissue-resident memory T cells
Hobbit
Blimp1
Runx3
Notch1
Lead sponsor: Universidad Autonoma de San Luis Potosí
Sponsor class: OTHER
First posted: 2022-08-18
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with clinical diagnosis of vitiligo vulgaris with more than 10 percent of the total body surface affected.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Tissue-resident memory T cells
timeFrame: Up to 1 year
Secondary outcomes:
measure: Tissue-resident memory T cells among the repigmentation patterns
timeFrame: Up to 1 year
measure: Arrangment of the Tissue-resident memory T cells among the repigmentation patterns
timeFrame: Up to 1 year
measure: TRM transcriptional factors profile
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: San Luis Potosí
country: Mexico
facility: Dermatology Department. Hospital Central "Dr. Ignacio Morones Prieto"
Study officials:
affiliation: Universidad Autonoma de San Luis Potosi
name: Juan P Castanedo-Cazares, MD
role: PRINCIPAL_INVESTIGATOR
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