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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 34  |  Issue : 2  |  Page : 494-497

Role of high mobility group box 1 in vitiligo


1 Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Medical Biochemistry, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission01-Dec-2019
Date of Decision04-Feb-2020
Date of Acceptance08-Feb-2020
Date of Web Publication30-Jun-2021

Correspondence Address:
Eman El-Sayed Ahmed Ghoniem
MBBCh, El-Shohadaa, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_363_19

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  Abstract 


Objectives
To assess the role of high-mobility group box 1 (HMGB1) in the pathogenesis of vitiligo patients and its relation to severity of vitiligo.
Background
Vitiligo is a chronic inflammatory disease characterized by skin depigmentation caused by the loss of epidermal melanocytes. Its prevalence ranges between 0.5 and 2%. The pathogenesis of vitiligo is poorly understood.
Patients and methods
This is a case–control study that was conducted on 80 participants, who were divided into two main groups. The first group A included 40 patients with vitiligo. The second group B included 40 age-matched and sex-matched healthy participants as a control group. Blood sample was taken from each participant for measurement of plasma HMGB1 level by the enzyme-linked immunosorbent assay technique.
Results
The result showed significant increase in the level of plasma HMGB1 in vitiligo patients (79.48 ± 110.5) compared with controls (51.70 ± 69.16) (P = 0.040). The result also showed that HMGB1 concentration was not correlated with clinical parameters such as age, sex, disease onset, duration of recent aggravation, or percentage of vitiligo involvement.
Conclusion
Our data provide insights into the possible role of HMGB1 for the pathogenesis of vitiligo.

Keywords: high-mobility group bo × 1, pathogenesis, vitiligo


How to cite this article:
Basha MA, Elgayed EM, Ghoniem EE. Role of high mobility group box 1 in vitiligo. Menoufia Med J 2021;34:494-7

How to cite this URL:
Basha MA, Elgayed EM, Ghoniem EE. Role of high mobility group box 1 in vitiligo. Menoufia Med J [serial online] 2021 [cited 2024 Mar 29];34:494-7. Available from: http://www.mmj.eg.net/text.asp?2021/34/2/494/319723




  Introduction Top


Vitiligo is the most common acquired idiopathic depigmentary disorder characterized by amelanotic macules and patches of the skin, hair, and mucous membranes due to selective destruction of melanocytes [1]. Its prevalence ranges between 0.5 and 2% [2]. The pathogenesis of vitiligo is poorly understood but a number of mechanisms such as oxidative stress, autoimmunity, autocytotoxicity, genetic factors, neural, and melanocytorrhagy have been proposed for the pathogenesis of vitiligo [3]. The lack of pigmentation may be attributed to two main causes: absence of melanocytes and/or the inability of melanocytes to produce and store melanin in melanosomes in the process of melanogenesis [4]. High-mobility group box 1 (HMGB1) is a nonhistone DNA-binding protein active in the bending of DNA and in its transcription[5] that participates in a number of physiological and pathological processes, including cytokine production, cell proliferation, angiogenesis, cellular differentiation, and cell death [6],[7]. Normally it is found in the nucleus, although cytoplasmic translocation may be stimulated by external stresses or release of cytokines from the surrounding cells. HMGB1 may also breach extracellular space upon cell death via necrosis or apoptosis [8],[9]. Extracellular HMGB1 binds to receptors for advanced glycation end products on cell surfaces to induce cellular signaling in inflammation, cell differentiation, and cell migration [10],[11]. Many external stresses, which include reactive oxygen species from ultraviolet (UV) irradiation and intracellular enzymatic reactions, are known to stimulate secretion of HMGB1 from many cells, such as macrophages, monocytes, and neutrophils [12],[13]. Secretion of HMGB1 from keratinocytes is also induced by UVB irradiation, potentially linking HMGB1 with certain pathological conditions of the skin [14]. Released HMGB1 may act as a damage-associated molecular pattern molecule, inducing immune responses through proinflammatory molecular production. Mounting evidence suggests that HMGB1 is involved in assorted autoimmune diseases [15]. The aim of this study was to assess the role of HMGB1 in the pathogenesis of vitiligo patients and its relation to severity of vitiligo.


  Patients and methods Top


This study was carried out at the Dermatology, Andrology and STDs and Medical Biochemistry and Molecular Biology Departments, Faculty of Medicine, Menoufia University. This study included 80 patients who were divided into two groups:

  1. Group A: 40 patients with vitiligo as the patient group.
  2. Group B: 40 age-matched and sex-matched healthy volunteers as a control group.


A written informed consent was taken from every participant participated in this study. The protocol was approved by the ethics committee of medical research of Menoufia Faculty of Medicine.

Inclusion criteria

  1. All cases of vitiligo (segmental or nonsegmental).


Exclusion criteria

  1. Concomitant autoimmune disease.
  2. Malignancy.
  3. Symptoms of any infection.


All participants were subjected to the following:

  1. Full history taking, complete general examination, dermatological examination.
  2. Laboratory investigations including measurement of HMGB1 plasma levels by enzyme-linked immunosorbent assay (ELISA) technique.


Samples collection

From each participant in the study, 3 ml of venous blood was withdrawn under complete aseptic condition. Samples were dispensed in EDTA tubes and then the samples were centrifuged at 3000 rpm for 15 min and serum was kept frozen at − 20°C until analysis.

Measurement of high-mobility group bo × 1 plasma levels

HMGB1 levels were measured by the ELISA kit (Sunred Company, Shanghai, China).

Statistical analysis

The collected data were analyzed using the International Business Machines Statistical Package for the Social Sciences (IBM SPSS) software package, version 20.0. (IBM Corp., Armonk, New York, USA). Two types of statistical analysis were done: (a) descriptive statistics, for example number, percentage (%), arithmetic mean, which was used as a measure of central tendency and SD, which was used as a measure of dispersion, median, and range. (b) Analytic statistics, for example, Mann–Whitney test for abnormally distributed quantitative variables to compare between two studied groups; χ2 test for categorical variables to compare between different groups; Student's t test for normally distributed quantitative variables to compare between two studied groups; Kruskal–Wallis test was used to assess the statistical significance of the difference between more than two study group ordinal variables and Spearman's correlation coefficient (r) was used to measure the association between two quantitative variables not normally distributed or one quantitative and other qualitative variables.

P value: level of significance:

  1. P value more than 0.05: nonsignificant (NS).
  2. P value less than 0.05: significant (S).



  Results Top


This study included a total of 80 patients who were divided into two groups. Group A included 17 (42.5%) men and 23 (57.5%) women; their age ranged from 7 to 72 years with a mean ± SD age of 26.15 ± 17.84 years. Group B (the control group) included 23 (57.5%) men and 17 (42.5%) women; their age ranged from 7 to 65 years with a mean ± SD age of 28.23 ± 17.75 years [Table 1]. As regards the clinical pattern of vitiligo lesions, vitiligo vulgaris (70%) was the most common type observed in our study followed by focal and acrofacial. In this study, distribution of the disease (vitiligo area scoring index score) ranged from 0.750 to 38% of body surface area with a mean of 5.17 ± 8.45. The mean duration of illness for the patient group was 6.93 ± 2.93 years. Regarding the family history of vitiligo in this study, 7.5% of vitiligo was seen with a positive family history. The study results showed that there was significant increase in the level of plasma HMGB1 in vitiligo patients mean ± SD = 79.48 ± 110.5 compared with controls 51.70 ± 69.16 (P = 0.040) [Table 2]. HMGB1 concentration was not correlated with clinical parameters such as age, sex, disease onset, duration of recent aggravation, or percentage of vitiligo involvement [Table 3] and [Table 4].
Table 1: Comparison between vitiligo patients and control groups regarding socioeconomic data

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Table 2: Comparison between vitiligo patients and control group as regards serum high-mobility group box 1 level

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Table 3: Relation between mean high-mobility group box 1 level and clinical data of studied vitiligo patients (n=40)

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Table 4: Correlation between high-mobility group box 1 level and other factors such as age, duration of diseases, and vitiligo area scoring index score in vitiligo patients

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  Discussion Top


Vitiligo is a common skin and mucous-membrane depigmentation disease[16] that is characterized by well-circumscribed depigmented macules and patches [17]. HMGB1 is a DNA-binding protein that acts as a transcriptional regulator participating in DNA replication, recombination, transcription, and repair. In addition to its nuclear functions, extracellular HMGB1 released from activated immune cells, necrotic or injured cells, becomes a proinflammatory mediator through binding to cell-surface receptors of responding cells [18]. It has already been shown to be increased in the sera of patients with different other autoimmune-related chronic inflammatory disorders such as lupus erythematosus, rheumatoid arthritis, systemic sclerosis, or Sjogren's syndrome [19],[20]. In this study, there is significant elevation of the plasma level of HMGB1 in vitiligo patients compared with controls. This was consistent with Kim et al.[3] who found that in the ELISA technique for measurement of HMGB1 concentration in the plasma, patients with vitiligo showed significantly higher concentrations of HMGB1 than healthy controls. Zhang et al.[21] also found that in the ELISA technique for measurement of HMGB1 concentration in the plasma, patients with vitiligo showed significantly higher concentrations of HMGB1 than healthy controls. Generally, HMGB1 localizes in the nucleus and is a vital regulator of gene transcription by interacting with the chromatin structures of DNA [22]. However, when cells are under endogenic or environmental stresses, HMGB1 can be either actively secreted or passively released upon cell death into the extracellular space, and then promote inflammation by integrating with Pattern recognition receptors (PRRs) [23]. Kim et al.[3] propose that external stressors, such as UVB radiation and oxidative stress, both regarded as triggering factors in vitiligo stimulate HMGB1 release from keratinocytes leading to melanocyte apoptosis and decreasing the expression levels of melanogenesis-related molecules. Zhang et al.[21] reported that HMGB1 may be released from melanocytes exposed to UVB and promote the activation of extracellular signal-regulated kinase pathway in melanocytes in an autocrine way. HMGB1 secreted by melanocytes under oxidative stress is able to promote the secretion of chemokines from keratinocytes, which could induce cutaneous infiltration of CD8 T cells and maturation of DCs. The presentation of self-antigens derived from melanocytes via mature DCs is essential for the activation of cytotoxic T cells that target melanocytes in vitiligo [24]. Secretion of HMGB1 from keratinocytes and melanocytes under oxidative stress explains the increased plasma level of HMGB1 in vitiligo patients. HMGB1 concentration was not correlated with clinical parameters such as age, sex, disease onset, duration of recent aggravation, or percentage of vitiligo involvement. This was consistent with Kim et al.[3] who found that the HMGB1 concentration was not correlated with clinical parameters such as age, sex, disease onset, duration of recent aggravation, or percentage of vitiligo involvement. However, Zhang et al.[21] have found that HMGB1 plasma level increased in patients in the active progressive phase, but showed no change in the slowly progressive phase, which indicates that HMGB1 is a crucial inflammatory factor involved in the progression of vitiligo. Therefore, plasma HMGB1 level is a promising biomarker for monitoring disease activity in patients with vitiligo.


  Conclusion Top


HMGB1 is a crucial damage-associated molecular pattern molecule that links oxidative stresses to the formation of autoimmunity in the pathogenesis of vitiligo.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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