Leucine-rich glioma inactivated 3: a novel keratinocyte-derived melanogenic cytokine in vitiligo patients

Farag, Azza Gaber Antar; Hammam, Mostafa Ahmed; Al-Sharaky, Dalia Rifaat; El-Boghdady, Ghada Mohamed

doi:10.1590/abd1806-4841.20198250

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Investigation • An. Bras. Dermatol. 94 (4) • Jul-Aug 2019 • https://doi.org/10.1590/abd1806-4841.20198250 copy

Leucine-rich glioma inactivated 3: a novel keratinocyte-derived melanogenic cytokine in vitiligo patients^* * Study conducted at the Dermatology, Andrology and STDs department, Pathology Department, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt.

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract:

Background:

In-vitro studies showed that Leucine-rich glioma inactivated 3 (LGI3) is a keratinocyte-derived cytokine that stimulates melanin synthesis and is increased after ultra violet B (UVB) irradiation. So, we postulated that LGI3 may be involved in vitiligo aetiopathogenesis and may participate in narrow band ultra violet B (NB-UVB) induced pigmentation in vitiligo.

Objectives:

To assess this hypothesis, lesional LGI3 immunohistochemical expression of vitiligo patients before and after NB-UVB phototherapy was studied, and its correlation with repigmentation was evaluated.

Methods:

Forty vitiligo patients and 20 age, sex, and skin phenotype-matched controls were enrolled. Patients were treated with NB-UVB thrice weekly for 12 weeks. VASI score was evaluated before and after NB-UVB sessions. For vitiligo patients, baseline LGI3 immunohistochemical staining was estimated, and compared to that of controls and to its post-treatment data in those patients. Results: Baseline LGI3 immunohistochemical studied parameters (expression, intensity, percentage and H score) were significantly lower in vitiligo cases than controls (p=0.003, 0.013, 0.001 and 0.001 respectively). After 12 weeks of NB-UVB phototherapy, these LGI3 immunohistochemical parameters were up-regulated and became comparable to that of controls (p >0.05 for all). There was a significant positive correlation between the improvement of both VASI score and LGI3 H score mean values (r=-0.349 , p=0.027).

Study limitations:

Small number of investigated subjects.

Conclusions:

Decreased LGI3 protein may play an active role in vitiligo pathogenesis and its up-regulation after NB-UVB phototherapy, may actively participate in NB-UVB photo-induced melanogenesis.

Keywords:
Phototherapy; Skin pigmentation; Vitiligo

Evaluated data	Studied group N=60				Test of significance	P value
	Cases n=40		Control n=20
Age
Mean ± SD	33.9±11.38		37.40±10.58		U	0.249
Range	15.0-50.0		20.0-50.0		1.15
Median	32.0		35.0
Sex	NO	%	NO	%	χ²	0.464
Male	20	50.0	12	60.0	0.536
Female	20	50.0	8	40.0
Occupation					0.313	0.576
Outdoor	17	42.5	7	35.0
Indoor	23	57.5	13	65.0
Skin type					0.967	0.616
II	10	25.0	4	20.0
III	19	47.5	8	40.0
IV	11	27.5	8	40.0
Family history of vitiligo			---	------	---	---
Positive	2	5.0
Negative	38	95.0
Type of vitiligo			---	---	---	---
Segmental	16	40.0
Non-segmental	24	60.0
Disease duration (years)		---	---	---	---	---
Mean ± SD	3.48±5.59
Range	0.25-24.0
Median	1.0
Age of onset (years)		---	---	---	---	---
Mean ± SD	30.55± 11.01
Range	14.0-50.0
Median	28.0
VASI score before phototherapy		---	---	---	---	---
Mean±SD	3.74±2.29
Range	0.9-10.8
Median	3.6

Immunohistochemical staining	Studied group (N=60)						Test of Significance	p-value
	Controls n=20		Cases before treatment n=40		Cases after treatment n=40
Expression	NO	%	NO	%	NO	%	T1=χ²=8.29	P1=0.003^* * Significant.
Positive	20	100	27	67.5	37	92.5	T2=Mc Nemar χ²=10.58	P2=0.001^* * Significant.
Negative	0	0.0	13	32.5	3	7.5	T3= χ²=1.85	P3=0.554
Localization
Cytoplasmic	18	90	24	88.9	31	83.8	T1= χ²=0.83	P1=0.659
Membranous	0	0	1	3.7	1	2.7	T2=MH=0.447	P2=0.655
Membrano-cytoplasmic	2	10	2	7.4	5	13.5	T3= χ²=0.73	P3=0.694
Intensity
Mild	10	50.0	22	81.5	18	48.6	T1= χ²=8.65	P1=0.013^* * Significant.
Moderate	5	25.0	5	18.5	14	37.8	T2=MH=2.99	P2=0.003^* * Significant.
Strong	5	25.0	0	0.0	5	13.5	T3= χ21.62	P3=0.444
Distribution							T1= χ²=0.366	P1=0.545
Patchy	14	70.0	21	77.8	20	54.05	T2=Mc Nemar χ²=6.50	P2=0.011^* * Significant.
Diffuse	6	30.0	6	22.2	17	45.9	T3= χ²=1.37	P3=0.242
Percentage
Mean ± SD	40.25±26.83		18.22±18.44		39.07±24.89		T1=U=116.00	P1=0.001^* * Significant.
Range	10.0-85.0		2.0-70.0		2.0-95.0		T2=Wilcoxon signed rank=4.29	P2=0.001^* * Significant.
Median	30.0		10.0		30.0		T3=U=0.528	P3=0.597
H score
Mean ± SD	89.75±94.79		25.26±31.03		74.11±71.96		T1=U=3.39	P1=0.001^* * Significant.
Range	10.0-255.0		2.0-120.0		2.0-240.0		T2=Wilcoxon signed rank =4.38	P2=0.001^* * Significant.
Median	40.0		10.0		45.0		T3=U=0.570	P3=0.569

Sociedade Brasileira de Dermatologia Av. Rio Branco, 39 18. and., 20090-003 Rio de Janeiro RJ, Tel./Fax: +55 21 2253-6747 - Rio de Janeiro - RJ - Brazil
E-mail: revista@sbd.org.br

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[1] Mailing Address: Azza Gaber Antar Farag. E-mail: azzagaber92@yahoo.com

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Leucine-rich glioma inactivated 3: a novel keratinocyte-derived melanogenic cytokine in vitiligo patients* * Study conducted at the Dermatology, Andrology and STDs department, Pathology Department, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt.

Abstract:

Background:

Objectives:

Methods:

Study limitations:

Conclusions:

Leucine-rich glioma inactivated 3: a novel keratinocyte-derived melanogenic cytokine in vitiligo patients^* * Study conducted at the Dermatology, Andrology and STDs department, Pathology Department, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt.