Clinical trial NCT05698342: Tissue-resident Memory T Cells Expression in Melasma
Official title: Tissue-resident Memory T Cells Expression in Melasma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Melasma
Keywords: blimp-1
runx-3
transcription factors
tissue-resident memory T cells
Lead sponsor: Universidad Autonoma de San Luis Potosí
Sponsor class: OTHER
First posted: 2023-01-26
Enrollment: 20
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: female patients with malar melasma, healthy volunteers 18 years of age and older, without previous treatment or photoprotection measures within the previous 4 weeks, who had at least 7 Modified Melasma Activity and Severity Index (mMASI) score

Brief summary: The treatment of melasma and the maintenance of depigmentation represent a challenge due to its frequent recurrences. Pathophysiological mechanisms and factors have been linked to melasma such as inflammation, sun exposure, increased CD4+ T lymphocytic infiltrate and IL-17 in damaged skin. Tissue-resident memory T cells (Trm), derived from naïve T lymphocytes, are associated with the recurrence of lesions at the same sites but they have not been described in melasma. This a Cross-sectional, prospective analytical study. 20 female patients, 18 to 55 years of age, with diagnosis of melasma and mMASI score of at least 7, at least 1-year duration, lesional and perilesional skin biopsies were taken for PCR and DIF. The objective is to determine the transcription factors of Trm cells in malar melasma.

Detailed description: Melasma is a common, acquired pigmentary disorder characterized by chronic and relapsing hypermelanosis on sun-exposed areas that causes significant emotional and psychosocial impact in patients mainly in women with Fitzpatrick III-V phototypes. The treatment of melasma and the maintenance of depigmentation represents a challenge due to its frequent recurrences.

Different pathophysiological mechanisms and factors have been linked to melasma such as inflammation, sun exposure, increased CD4+ T lymphocytic infiltrate and IL-17 in damaged skin. In pathologies such as vitiligo and psoriasis, tissue-resident memory T cells (Trm), derived from naïve T lymphocytes, are associated with the recurrence of lesions at the same sites. These cells have a specific profile of transcription factors (Runx3+, Notch+, Blimp1+) and CD69 + CD103 + markers. These cells have not been described in melasma.

Objective: to determine the transcription factors of Trm cells in malar melasma. This is a Cross-sectional, prospective analytical study. 20 female patients, 18 to 55 years of age, with diagnosis of melasma and mMASI score of at least 7, at least1 year duration, and no treatment in the last 4 weeks, were included. Lesional and perilesional skin biopsies were taken for PCR and DIF. The presence of trm cells has not been described or studied in melasma where there is recurrence of the dermatosis in the same site, it is essential to understand its pathogenesis in order to address directed future therapies targeting these cells that may related to the disease.

Eligibility criteria: Inclusion Criteria:

female patients with malar melasma, healthy volunteers 18 years of age and older, without previous treatment or photoprotection measures within the previous 4 weeks, who had at least 7 Modified Melasma Activity and Severity Index (mMASI) score

Exclusion Criteria:

* Exclusion criteria were pregnancy or nursing, menopause, coexistence of other pigmentation conditions, heat exposure, regular exer- cise, diet restriction, consumption of food supplements or any type of drugs (including anti-inflammatories and hormonal treatments) within the previous 2 months, and women who had given birth within 1 year

Primary outcomes:
measure: Tissue-resident memory T cells
timeFrame: up to 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: San Luis Potosí
country: Mexico
facility: Dermatology Department. Hospital Central "Dr. Ignacio Morones Prieto"
Study officials:
References:
citation: Filoni A, Mariano M, Cameli N. Melasma: How hormones can modulate skin pigmentation. J Cosmet Dermatol. 2019 Apr;18(2):458-463. doi: 10.1111/jocd.12877. Epub 2019 Feb 18.
citation: Hernandez-Barrera R, Torres-Alvarez B, Castanedo-Cazares JP, Oros-Ovalle C, Moncada B. Solar elastosis and presence of mast cells as key features in the pathogenesis of melasma. Clin Exp Dermatol. 2008 May;33(3):305-8. doi: 10.1111/j.1365-2230.2008.02724.x.
citation: Rodriguez-Arambula A, Torres-Alvarez B, Cortes-Garcia D, Fuentes-Ahumada C, Castanedo-Cazares JP. CD4, IL-17, and COX-2 Are Associated With Subclinical Inflammation in Malar Melasma. Am J Dermatopathol. 2015 Oct;37(10):761-6. doi: 10.1097/DAD.0000000000000378.
citation: Lee HC, Thng TG, Goh CL. Oral tranexamic acid (TA) in the treatment of melasma: A retrospective analysis. J Am Acad Dermatol. 2016 Aug;75(2):385-92. doi: 10.1016/j.jaad.2016.03.001. Epub 2016 May 17.
citation: Tokura Y, Phadungsaksawasdi P, Kurihara K, Fujiyama T, Honda T. Pathophysiology of Skin Resident Memory T Cells. Front Immunol. 2021 Feb 3;11:618897. doi: 10.3389/fimmu.2020.618897. eCollection 2020.
citation: Watanabe R, Gehad A, Yang C, Scott LL, Teague JE, Schlapbach C, Elco CP, Huang V, Matos TR, Kupper TS, Clark RA. Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells. Sci Transl Med. 2015 Mar 18;7(279):279ra39. doi: 10.1126/scitranslmed.3010302.
citation: Zou Y, Yuan H, Zhou S, Zhou Y, Zheng J, Zhu H, Pan M. The Pathogenic Role of CD4+ Tissue-Resident Memory T Cells Bearing T Follicular Helper-Like Phenotype in Pemphigus Lesions. J Invest Dermatol. 2021 Sep;141(9):2141-2150. doi: 10.1016/j.jid.2021.01.030. Epub 2021 Mar 16.
citation: Fraczek A, Owczarczyk-Saczonek A, Placek W. The Role of TRM Cells in the Pathogenesis of Vitiligo-A Review of the Current State-Of-The-Art. Int J Mol Sci. 2020 May 18;21(10):3552. doi: 10.3390/ijms21103552.
citation: Adachi T, Kobayashi T, Sugihara E, Yamada T, Ikuta K, Pittaluga S, Saya H, Amagai M, Nagao K. Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma. Nat Med. 2015 Nov;21(11):1272-9. doi: 10.1038/nm.3962. Epub 2015 Oct 19.