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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 46  |  Issue : 2  |  Page : 139-144

Serum galectin-9 level in patients with atopic dermatitis


1 Department of Dermatology and Venereology, Tanta University Hospital, Tanta, Egypt
2 Department of Clinical Pathology, Tanta University Hospital, Tanta, Egypt
3 Department of Dermatology and Venerology, Kafr Elsheikh Dermatology Hospital, Tanta, Egypt

Date of Submission26-Jul-2017
Date of Acceptance02-Jan-2018
Date of Web Publication31-Oct-2018

Correspondence Address:
Shaimaa E Elgedawy
Mahallet Ziad, Samannoud, Gharbia Governorate, 31816
Egypt
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DOI: 10.4103/tmj.tmj_71_17

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  Abstract 


Background Atopic dermatitis (AD) is a common chronic inflammatory skin disease of unknown etiology. It is characterized by peripheral eosinophilia, mast cell activation, and predominance of T-helper-2 cells. Galectin-9 is a potent eosinophilic chemoattractant. It also alters T-cell balance by negatively regulating T-helper cells, resulting in T-helper-2 polarization. Inhibition of endogenous galectin-9 may improve the course of the disease.
Aim The aim of this study was to evaluate serum level of galectin-9 in patients with AD to assess its possible role in pathogenesis of the disease.
Patients and methods The current study included 20 patients with AD and 10 age-matched and sex-matched healthy individuals who served as a control group. Patients were divided into three groups, mild, moderate, and severe, according to their Six-Area, Six-Sign Atopic Dermatitis score. Peripheral venous blood sample was taken from each participant, and serum was examined by enzyme-linked immunosorbent assay for quantitative evaluation of galectin-9.
Results Galectin-9 was significantly increased in patients with AD compared with the control group. The difference between the three studied groups was statistically significant regarding serum galectin-9 level. There was significant positive correlation between serum galectin-9 level and severity of the disease. In contrast, no significant correlations were found between serum galectin-9 level and age, sex of the patients, and duration of the disease.
Conclusion Serum galectin-9 level was significantly elevated in patients with AD. This increase was positively correlated with disease severity. This suggests a possible role of galectin-9 in the pathogenesis of AD. New treatment strategies that are directed toward lowering galectin-9 level may be a hope for future perspectives of the treatment of AD.

Keywords: atopic dermatitis, galectins, Six-Area Six-Sign Atopic Dermatitis, T-cell immunoglobulin mucin-3


How to cite this article:
Amin TE, Hodeib AA, Elsharnouby JA, Elgedawy SE. Serum galectin-9 level in patients with atopic dermatitis. Tanta Med J 2018;46:139-44

How to cite this URL:
Amin TE, Hodeib AA, Elsharnouby JA, Elgedawy SE. Serum galectin-9 level in patients with atopic dermatitis. Tanta Med J [serial online] 2018 [cited 2018 Nov 21];46:139-44. Available from: http://www.tdj.eg.net/text.asp?2018/46/2/139/244691




  Introduction Top


Atopic dermatitis (AD) is a pruritic disease of unknown origin that usually starts in early infancy, though an adult-onset variant has been recognized. This is the first disease to present in a series of allergic diseases, that include food allergy, asthma, and allergic rhinitis, in order of presentation, which has given rise to the ‘atopic march’ theory. It has been suggested that AD is part of a progression that may lead to subsequent allergic disease at other epithelial-barrier surfaces [1],[2].

Two main hypotheses have been proposed regarding the development of inflammation that leads to AD. The first hypothesis suggests a primary immune dysfunction resulting in immunoglobulin E sensitization and secondary epithelial-barrier disturbance. The second hypothesis proposes a primary defect in the epithelial barrier leading to secondary immunologic dysregulation and resulting in inflammation [3].

Galectins are a large family proteins with relatively broad specificity. They have a broad variety of functions including mediation of cell–cell interactions, cell–matrix adhesion, and transmembrane signaling. Their expression and secretion are well regulated, suggesting that they may be expressed at different times during development [4]. Galectins can regulate cell death both intracellularly and extracellularly. Extracellularly, they cross-link glycans on the outside of cells and transduce signals across the membrane to directly cause cell death or activate downstream signaling that triggers apoptosis. Intracellularly, they can directly regulate proteins that control cell fate. So, galectins have a vital role in apoptosis. One essential way by which galectins regulate apoptosis is by controlling positive and negative selection of T cells in the thymus. This process prevents the circulation of T cells that are self-reactive and recognize self-antigen [5].

Galectin-9 (Gal-9) is secreted by epithelial cells in the thymus and mediates T-cell apoptosis. T-cell death is also necessary to kill activated and infected T cells after an immune response. Gal-9 has been well characterized as an eosinophilic chemoattractant. Inhibition of endogenous Gal-9 function may improve the disease course of AD [6].


  Aim Top


The aim of this study was to evaluate serum level of Gal-9 in patients with AD to assess its possible role in pathogenesis of the disease.


  Patients and methods Top


This study was carried out on 20 patients with AD who were recruited from the outpatient clinic of Dermatology and Venereology Department, Tanta University Hospitals. In addition, 10 age-matched and sex-matched healthy individuals were recruited who served as a control group.

The patient group included 11 males and nine females. Their ages ranged between 3 months and 25 years. The diagnosis of AD was based on Hanifin and Rajka criteria for AD [7]. The control group included five males and five females with no past or family history of atopic disorders. Their ages ranged between 5 months and 26 years.

Inclusion criteria

The following were the inclusion criteria:
  1. Patients with different stages and severity of the disease.
  2. Patients who accepted to be enrolled in the study and signed informed consents.


Exclusion criteria

The following were the exclusion criteria:
  1. Patients who received any topical or systemic treatment for AD during the past 6 weeks before the study.
  2. Patients with history of drug or alcohol dependency or cigarette smokers.
  3. Patients with other dermatological diseases that may affect serum Gal-9 such as systemic lupus erythematosus and viral infection such as herpes simplex virus and HIV.
  4. Patients with any systemic diseases that may affect serum Gal-9 level such as autoimmune diseases, coronary artery disease, and various cancers (hepatocellular carcinoma, cholangiocarcinoma, or hematologic malignancies).
  5. Patients under NSAIDs or antioxidants, as they may affect the serum level of Gal-9.


All participants were subjected to the following:
  1. Complete history taking:
    1. Personal history included name, age, sex, occupation, and special habits.
    2. Present history included onset, course, and duration of the disease.
    3. Family history of AD or other allergic diseases.
    4. Past history of similar condition.
  2. Thorough general and dermatological examination was done to exclude any systemic or dermatological diseases:
    1. Patients were examined for the site, morphology, and distribution of the lesions.
    2. The severity of the disease was assessed using Six-Areas Six-Signs Atopic Dermatitis (SASSAD) severity score [8]. The patients were classified into mild (SASSAD score<20), moderate (SASSAD score=20–40), and severe (SASSAD score>40).
  3. Laboratory investigations: routine laboratory investigations included complete blood count, random blood glucose level, lipid profile, liver and renal function tests, along with determination of the serum level of Gal-9 by enzyme-linked immunosorbent assay for quantitative detection of human Gal-9 were done [9].
  4. Statistical presentation and analysis of the study were conducted using the mean value, SD, χ2-test and linear correlation coefficient (r) by SPSS, Newtest company Egypt, V.16.



  Results Top


Clinical results

The present study included 20 patients with AD and 10 age-matched and sex-matched healthy persons serving as controls.

Control group

This group included five (50%) males and five (50%) females. Their ages ranged from 5 months to 26 years, with a mean of 10.48±10.97 years. They included three (30%) infants, three (30%) children, and four (40%) adults ([Table 1]).
Table 1 Demographic data of the studied groups

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Patients group

This group included 20 patients with AD, with 11 (55%) males and nine (45%) females. Their ages ranged from 3 months to 25 years, with mean of 9.77±9.28 years. They included six (30%) infants, seven (35%) children, and seven (35%) adults. Comparison between patients and control groups regarding the age and sex revealed no significant difference ([Table 1]).

Duration of the disease ranged from 2 months to 20 years, with a mean of 5.87±5.86 years. There was a positive personal history of other atopic disorders in nine (45%) patients, in the form of allergic rhinitis in seven (35%) patients and asthma in two (10%) patients. Family history of atopic diseases was positive in 11 (55%) patients only ([Table 2]).
Table 2 Clinical parameters of the studied patients

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Patients were classified according to SASSAD score into mild, moderate, and severe. The score ranged from 10 to 42, with mean of 29.05±10.87. Mild AD group included five (25%) patients. Of them, one (20%) was infant, two (40%) were children, and two (40%) were adults. Moderate AD group included nine (45%) patients. Of them, there were three (33.3%) infants, three (33.3%) children, and three (33.3%) adults. Severe AD group included six (30%) patients. Of them, there were two (33.3%) infants, two (33.3%) children, and two (33.3%) adults ([Table 3] and [Table 4]).
Table 3 Data of the studied patients according to Six-Area, Six-Sign Atopic Dermatitis score

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Table 4 Relation between disease severity and age in patients group

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Laboratory results

Routine laboratory investigations including complete blood count, random blood glucose level, lipid profile, liver and renal function tests were within normal limits.

Serum Gal-9 in patients group ranged from 414.8 to 1296.3 pg/ml, with a mean of 872.44±252.49 pg/ml. In contrast, serum Gal-9 in control group ranged from 121.9 to 351.6 pg/ml, with a mean of 269.94±81.71 pg/ml. There was statistically significant increase in serum Gal-9 in patients compared with control (P<0.001) ([Table 5]).
Table 5 Comparison between the studied groups according to serum galectin-9 level

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In the 11 studied male patients, serum Gal-9 level ranged from 547.2 to 1121.5 pg/ml, with a mean of 833.75±179.1 pg/ml, whereas in the nine studied female patients, it ranged from 414.8 to 1296.3 pg/ml, with a mean of 919.72±326.71 pg/ml. There was no significant difference between serum Gal-9 in male and female patients (P=0.464) ([Table 6]).
Table 6 Relation between serum galectin-9 level and sex in patients group

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In the 11 studied patients with negative personal history of other atopic diseases, serum Gal-9 level ranged from 414.8 to 1296.3 pg/ml, with a mean of 840.35±284.55 pg/ml. In the seven studied patients with allergic rhinitis, serum Gal-9 level ranged from 1508 to 2160.3 pg/ml, with a mean of 1759.52±317.8 pg/ml. In the two studied patients with asthma, serum Gal-9 level ranged from 760 to 1121.5 pg/ml, with a mean of 940.75±255.62 pg/ml. There was no significant difference between serum Gal-9 levels in different groups of present history of other atopic diseases ([Table 7]).
Table 7 Relation between serum galectin-9 level and family history of atopy, personal history of atopy, and disease severity in patients group

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Serum Gal-9 level in the 11 studied patients with positive family history of atopic diseases ranged from 547.2 to 1296.3 pg/ml, with a mean of 916.92±193.95 pg/ml, whereas in the nine studied patients with negative family history of atopic diseases, it ranged from 414.8 to 1255.8 pg/ml, with a mean of 818±313.59 pg/ml. There was no significant difference of serum Gal-9 level in patients with positive family history of atopy than in patients with negative family history ([Table 7]).

Regarding relation between serum Gal-9 and severity of the disease in patients group, serum Gal-9 level in the mild AD group ranged from 414.8 to 682.9 pg/ml, with a mean of 533.18±102.44 pg/ml. In the moderate AD group, it ranged from 760 to 951 pg/ml, with a mean of 875.83±64.24 pg/ml, whereas in the severe AD group, it ranged from 977.1 to 1296.3 pg/ml, with a mean of 1150.05±140.19 pg/ml. There was significant difference in serum Gal-9 level between mild and moderate, between mild and severe, and between moderate and severe ([Table 7]).

Regarding correlations between serum Gal-9 level and different parameters in patients group, there was no significant correlation between serum Gal-9 level and age (r=0.008 and P=0.975) and duration of the disease (r=0.154 and P=0.518). There was significant positive correlation between serum Gal-9 level and severity of the disease (rs=0.932 and P<0.001) ([Table 8]).
Table 8 Correlation between serum galectin-9 and different parameters in patients group

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  Discussion Top


AD is a chronic, highly pruritic, inflammatory skin disease. It is characterized by periods of remission and relapse. The clinical phenotype that characterizes AD is the product of complex interactions among susceptibility genes, the host’s environment, defects in skin barrier function, as well as systemic and local immunologic responses [10].

AD is often the first step in the atopic march that results in asthma and allergic rhinitis in many of affected patients. It has been recognized as Th-2 disease for the abundant secreation of Th-2 cytokines; interleukin (IL)-4, IL-5, and IL-13 associated with eosinophilia; and elevated serum immunoglobulin E level [11].

Gal-9 is a member of the tandem-repeat galectin family [12]. Gal can regulate multiple physiological and pathological processes including allergy [13]. Gal-9 has been well characterized as an eosinophilic chemoattractant [6]. It alters T-cell balance by negatively regulating Th-1 and Th-17 cells, resulting in Th-2 polarization [13].

The aim of this work was to evaluate serum level of Gal-9 in patients with AD to assess its possible role in the pathogenesis of the disease.

The present study included 20 patients of AD and 10 healthy participants of matched age and sex who served as controls. The age of the patients ranged from 3 months to 25 years, as they were selected according to their ages to include all types of AD. AD occurs primarily in childhood affecting 15–30% of children and 2–10% of adults and most frequently begin in early childhood, with 45% of cases occurring within the first 6 months of life whereas 85% of cases diagnosed within the first 5 years [14]. The study included 11 (55%) male and nine (45%) female patients. This result was similar to Thomas and Myalil [15] who reported that male to female ratio in AD is 1.5 : 1. Selcuk et al. [16] and Shultz et al. [17] reported a male predominance. In contrast, Kim et al. [18], Edan et al. [19], and Williams et al. [20] reported higher AD prevalence in girls than in boys. In contrast, Johnston et al. [21], Saito [22], and Larsen and Hanifin [23] reported that both sexes are equally affected with AD. This wide range of results may be attributed to different race, education, and environmental factors of different studies.

The present study showed statistically significant increase of mean serum Gal-9 in patients with AD in comparison with controls. Significant positive correlation has been reported between serum Gal-9 level and the severity of the AD as evaluated by SASSAD score. This result agreed with Nakajima et al. [24] who reported that mean serum Gal-9 level was significantly increased in patients with AD than in controls. They suggested that Gal-9 is a potent chemoattractant for eosinophils in AD. In addition, it alters T-cell balance by negatively regulating T-helper Th-1 and Th-17 cells, resulting in Th-2 polarization. They also reported that serum Gal-9 levels were decreased after treatment, accompanied by improvement of skin lesions. This strongly indicates that serum Gal-9 levels correlate with disease activity.

Few articles discussed the evaluation of serum Gal-9 level in AD. In contrast, there are only few publications on Gal-9 in other atopic diseases with conflicting results reported [25],[26],[27]. Yamamoto et al. [27] showed that Gal-9 is not involved in airway hypersensitivity of guinea pig but is partly involved in prolonged eosinophil accumulation in the lung. In contrast, Chen et al. [26] documented that normal intestinal epithelial cells (IEC) show mild expression of Gal-9 that is markedly enhanced in patients with food allergy as mast cells induce IEC to produce Gal-9 via releasing tryptase that activated the proteinase-activated receptor 2 on IEC. Gal-9 activated dendritic cell to produce TIM-4 by ligating TIM3 on dendritic cell by activating the cyclic GMP pathway. In a mouse food allergy model, blocking Gal-9 inhibits the allergic hypersensitivity status and the antigen-specific Th-2 response in the intestine. Sziksz et al. [25] stated that Gal-9 plays a role as a mediator contributing to the development of allergic airway inflammation and may serve as a recruiter of eosinophil granulocytes and promoter of Th-2 dominance.

The previous data and results showed the possible role of Gal-9 in the pathogenesis of AD and its relation with disease activity.


  Conclusion Top


From this study, it can be concluded that serum Gal-9 level was significantly elevated in patients with AD. This increase was positively correlated with disease severity as evaluated by SASSAD score. This suggests a possible role of Gal-9 in the pathogenesis of AD. New treatment strategies directed to lower Gal-9 level may be a hope for future perspectives in the treatment of AD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Thomas IN, Myalil JM. How significant is family history in atopic dermatitis? a study on the role of family history in atopic dermatitis in children in Ajman, United Arab Emirates. Egypt Dermatol Online J 2010; 6:1–6.  Back to cited text no. 15
    
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Sziksz E, Kozma GT, Pállinger E, Komlósi ZI, Adori C, Kovács L et al. Galectin-9 in allergic airway inflammation and hyper-responsiveness in mice. Int Arch Allergy Immunol 2010; 151:308–317.  Back to cited text no. 25
    
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Chen X, Song CH, Liu ZQ, Feng BS, Zheng PY, Li P et al. Intestinal epithelial cells express galectin-9 in patients with food allergy that plays a critical role in sustaining allergic status in mouse intestine. Allergy 2011; 66:1038–1046.  Back to cited text no. 26
    
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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