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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 46  |  Issue : 4  |  Page : 249-254

Plasma galectin-3-binding protein level in patients with systemic lupus erythematosus


1 Department of Dermatology, Basyeon Dermatology Hospital, Tanta, Egypt
2 Department of Dermatology and Venereology, Tanta University, Tanta, Egypt
3 Department of Clinical Pathology, Tanta University, Tanta, Egypt

Date of Submission10-Jul-2018
Date of Acceptance01-Dec-2018
Date of Web Publication02-Aug-2019

Correspondence Address:
MBBCH Samah Elsayed Abo-Elyazeed
Department of Dermatology, Basyeon Dermatology Hospital, Egypt
Egypt
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DOI: 10.4103/tmj.tmj_23_18

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  Abstract 


Background Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects multiple organs. It is characterized by production of autoantibodies and immune complex deposition in various organs, leading to inflammation and tissue destruction. Although the definite etiopathogenesis of SLE remains unclear, many different mechanisms may contribute to the pathogenesis of SLE. Galectin-3 is a member of beta-galactoside-binding lectins. It has an essential role in negatively regulating T-cell receptor.
Aim The aim of this work was to estimate the plasma level of galectin-3-binding protein (G3BP) in patients with SLE to assess its possible role in pathogenesis of the disease and its correlation to disease activity.
Patients and methods The current study included 25 patients with SLE and 25 healthy individuals who served as a control group. Patients were divided according to systemic lupus erythematosus disease activity index score. Peripheral venous blood samples were taken from each participant, and plasma was examined by enzyme-linked immunosorbent assay for quantitative evaluation of G3BP.
Results G3BP was significantly increased in SLE compared with control group. There was a significant positive relation between plasma G3BP level and family history. No significant correlation was found between plasma G3BP level and duration of the disease. A significant positive correlation was found between G3BP and activity of the disease according to systemic lupus erythematosus disease activity index.
Conclusion G3BP may play a role in the pathogenesis of SLE and may be useful for therapeutic intervention in patients with SLE.

Keywords: galectins, systemic lupus erythematosus, systemic lupus erythematosus disease activity index


How to cite this article:
Abo-Elyazeed SE, Gheida SF, Soliman GA, Gamea MM. Plasma galectin-3-binding protein level in patients with systemic lupus erythematosus. Tanta Med J 2018;46:249-54

How to cite this URL:
Abo-Elyazeed SE, Gheida SF, Soliman GA, Gamea MM. Plasma galectin-3-binding protein level in patients with systemic lupus erythematosus. Tanta Med J [serial online] 2018 [cited 2020 Feb 29];46:249-54. Available from: http://www.tdj.eg.net/text.asp?2018/46/4/249/263916




  Introduction Top


Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease affecting the connective tissue marked by alternate periods of remission and exacerbation [1]. It is characterized by production of autoantibodies directed against nuclear self-antigens leading to systemic inflammation and organ failure [2].

These autoantibodies can form immune complexes, which can be deposited in many tissues like skin and kidney [3]. Antinuclear autoantibodies and especially autoantibodies against double-stranded DNA represent a serological hallmark of SLE and may serve as indicators for disease activity and severity [4].

Pathophysiological mechanisms involved in breaking tolerance against self-components are not fully understood. However, in the past few years, disturbance in the clearance of apoptotic cells has been reported, and it has been suggested that apoptotic cells can serve as a source of autoantigens [5],[6].

Galectin-3, a member of the carbohydrate-binding protein family, shows high affinity for β-galactoside. It is mainly detected in the cytoplasm, as well as in nuclei and mitochondria [7],[8]. Galectin-3 is also secreted outside the cell [9].

The main biological function of galectin-3 is regulation of cell–cell cooperation, extracellular interactions during self/non-self-antigen, recognition and cellular activation, as well as mediating proliferation, differentiation, migration, and apoptosis [10].

High levels of galectin-3 have been found during chronic viral infections, in various types of solid cancers, Behcet’s disease, and rheumatoid arthritis (RA) [11].

The aim of the work was to estimate plasma level of galectin-3-binding protein (G3BP) in patients with SLE to assess its possible role in the pathogenesis of the disease and its correlation with disease activity.


  Patients and methods Top


This study was carried out on 25 patients with SLE recruited from the Outpatient Clinic of Dermatology and Venereology and Rheumatology Departments of Tanta University Hospitals after getting the approval from Tanta Faculty of Medicine Research Ethical committee. In addition, 25 healthy individuals of matched age and sex served as a control group.

The patient group included 22 females and three males. Their ages ranged between 17 and 45 years. The diagnosis of SLE was based on SLICC classification system [12]. The control group included 21 females and four males with no past or family history of autoimmune disorders. Their ages ranged between 17 and 41 years.

Inclusion criteria

The following were the inclusion criteria:
  1. Newly diagnosed cases of SLE.
  2. Patients diagnosed with SLE, with either quiescent or active form of the disease.


Exclusion criteria

The following were the exclusion criteria:
  1. Patients associated with other dermatological and systemic diseases that may affect plasma G3BP level, for example, RA, malignancy, psoriasis, and atopic dermatitis.
  2. Pregnant and lactating females.
  3. Patients who had taken corticosteroids, immunosuppressive, immunomodulators, dapsone, and antimalarial therapy within 1 month before the study were also excluded.


All participants were subjected to the following:
  1. Complete history taking.
  2. Thorough general and dermatological examination.
  3. Laboratory investigations as follows:
    1. Routine laboratory investigations, for example, complete blood picture, erythrocyte sedimentation rate, complete urine analysis, and renal and liver function tests.
    2. Laboratory investigations for diagnosis of SLE, for example, antinuclear autoantibodies and anti-double-stranded DNA.
    3. Specific laboratory investigations to measure plasma level of G3BP.



  Results Top


Clinical results

The present study included 25 patients with SLE and 25 healthy persons of matched age and sex serving as controls.

Control group

This group included 21 (84%) females and four (16%) males. Their ages ranged from 17 to 41 years, with a mean of 31.84±7.35 years ([Table 1]).
Table 1 Demographic data of the studied groups

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Patients group

This group included 25 patients with SLE, comprising 22 (88%) females and three (12%) males. Their ages ranged from 17 to 45 years, with mean of 30.36±8.10 years. Comparison between patients and control groups regarding the age and sex revealed no significant difference ([Table 1]).

Duration of the disease ranged from 3 weeks up to 7 years, with a mean of 1.87±1.83. In this study, seven (28%) patients had a positive family history, whereas 18 (72%) patients gave negative family history ([Table 2]).
Table 2 Clinical parameters of the studied patients

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Patients were classified according to systemic lupus erythematosus disease activity index (SLEDAI) score into mild, moderate, and severe. It ranged from 5 to 19, with a mean of 13.16±3.76. Thus, according to SLEDAI score, the current study included 12 (48%) patients with mild to moderate SLE and 13 (52%) patients with severe SLE ([Table 3]).
Table 3 Data of the studied patients according to systemic lupus erythematosus disease activity index score

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Laboratory results

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

In SLE group, plasma levels of G3BP ranged from 8.28 to 15.32 ng/ml, with a mean of 9.83±1.48 ng/ml, whereas in control group, they ranged from 0.21 to 8.75 ng/ml, with a mean of 5.11±2.90 ng/ml. So, the plasma levels of G3BP in patients with SLE were significantly higher than control group ([Table 4]).
Table 4 Comparison between the two studied groups according to galectin-3-binding protein level (ng/ml)

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Statistical analysis

Regarding the relation between plasma levels of G3BP and sex in patients with SLE, the difference was not statistically significant (P=0.770) ([Table 5]).
Table 5 Relation between galectin-3-binding protein level with sex, family history, and disease activity in patients group

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Regarding the relation between plasma levels of G3BP in patients with SLE and family history of the disease, patients with positive family history had significantly higher G3BP level compared with those patients with negative family history (P=0.008) ([Table 5]).

According to the relation between the activity of SLE and plasma levels of G3BP, patients with severe activity were significantly higher compared with those with mild to moderate activity (P=0.006) ([Table 5]).

There was no significant correlation between plasma level of G3BP and duration of the disease (r=0.015, P=0.943) ([Table 6]).
Table 6 Correlation between galectin-3-binding protein level (ng/ml) with duration (years) and systemic lupus erythematosus disease activity index score in patient group

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There was a significant positive correlation between plasma level of G3BP and SLEDAI score (r=0.505, P=0.010) ([Table 6]).


  Discussion Top


SLE is autoimmune disorder that affects multiple organs. It is characterized by production of autoantibodies and immune complex deposition in various organs, leading to inflammation and tissue destruction [13]. Its etiology is unknown; however, genetic, environmental, and immunological factors are proposed to contribute to breaking tolerance, resulting in the production of a variety of antibodies directed to self-components [3].

Pathophysiological mechanisms involved in breaking tolerance against self-components are not fully understood [4]; however, disturbance in the clearance of apoptotic cells has been reported, and it has been suggested that apoptotic cells can serve as a source of autoantigens [5],[6].

Galectin-3, a member of the galectin superfamily of beta-galactoside-binding lectins, mediates some of cellular functions including migration, adhesion, proliferation, and apoptosis [14],[15]. Galectin-3 has a CRD in the C-terminal region and structurally promotes pentamerization through its N-terminal domain, forming an extracellular lattice of galectin-3 and cross-linked glycans at the cell surface [16]. The resultant multivalent interactions establish extracellular microenvironments, regulating glycoprotein distribution and diffusion across the cell surface [17].

The aim of this work was to estimate plasma level of G3BP in patients with SLE to assess its possible role in the pathogenesis of the disease and its correlation to disease activity.

The current study was carried out on 25 patients with SLE and 25 healthy controls. Determination of plasma levels of G3BP was done in both patients and control by a quantitative enzyme-linked immunosorbent assay technique.

In the present study, there were 22 (88%) females and three (12%) males in patients with SLE, and this was in agreement with the previous reports, in which SLE is much more common in women than men (9 : 1) [18],[19]. Tsokos [20] reported that the ratio of women to men with SLE is ∼9 : 1, supporting a role for hormonal factors in disease induction and pathogenesis.

In the current study, positive family history was observed in 28% of patients with SLE. A study done by Caroline et al. [21] reported the frequency of family history of SLE in a cohort of 300 patients in London, United Kingdom, where 8% had at least one first-degree relative with SLE and 20–30% had a first-degree relative with other autoimmune diseases. This matched with Martens et al. [22] who reported that SLE has a familial association, and multiple genes such as class I, class II, and class III human leukocytic antigen genes appear to be responsible for a person developing lupus.

The present study showed statistically significant increase of mean plasma G3BP in patients with SLE in comparison with controls. This result agreed with Baechler et al. [23] who found that galectin-3 levels are increased in the serum of patients with SLE, possibly as a reflection of increased type 1 IFN activity, and Higgs et al. [24] found that increased activation of type 1 IFN system is a common dominator in rheumatic autoimmune diseases and is most increased in patients with SLE . Lee and colleagues reported increased levels of serum galectin-3 and good association between galectin-3 levels and disease activities in other autoimmune diseases. Another study showed that anti-galectin-3 autoantibody serum levels were significantly higher in patients with SLE than in healthy controls or in patients with other autoimmune diseases such as RA [25]. This finding indicates that galectin-3 may be an autoantigen in patients with SLE and be involved in the disease inflammatory process [26].

Nielsen and colleagues revealed an increased level of G3BP-positive microparticles either in sera or in electron-dense deposits from kidney biopsies of patients with SLE affected with lupus nephritis, suggesting that galectin-3 colocalizes in immune complex deposits. These results support the potential role of galectin-3 as a putative autoantigen in development of specific lupus manifestations [27].

Filer and colleagues demonstrated that increased galectin-3 levels in serum of patients with RA adds to the experimental and clinical evidence that galectin-3 plays a critical role in RA development, for example, by regulating RA synovial fibroblast functions. Thus, galectin-3 induces distinctive proinflammatory cytokine and chemokine expression profiles in RA synovial fibroblasts as compared with dermal fibroblasts [28]. In addition, Ohshima et al. [29] reported that galectin-3 and its binding protein is overexpressed in the RA synovial membrane, particularly at the invading pannus front, and that galectin-3 in the serum and synovial fluid is increased in patients with long-standing RA compared with osteoarthritis and healthy controls.

As far as clinical manifestations are concerned, the current study revealed no correlation between plasma level of G3BP and clinical manifestations. On the contrary, Shi and colleagues found correlation between anti-galectin-3 antibodies and SLE cutaneous vasculitis. Indeed, patients with SLE having skin lesions have high serum levels of anti-galectin-3 autoantibodies, which are localized on the vessel walls. Notably, the injection of anti-human galectin-3 antibodies in mice evoked a dermal vasculitis 36 h after injection [30].According to activity of the disease, this study found that plasma levels of G3BP were significantly higher in patients with severe SLE compared with those with moderate activity. In contrast to the results of the present study, Koca and colleagues stated that serum galectin-3 levels were elevated in patients with SLE nephritis versus healthy controls suggesting that galectin-3 might contribute to the inflammatory process. Nevertheless, galactin-3 exhibits insignificant correlation with disease activity and SLEDAI score [31].

The current study found a significant relation between plasma levels of G3BP and family history. There were no significant correlations between G3BP levels and duration of the disease. No available data in the literature have discussed these correlations.

The previous data and results showed the possible role of G3BP in the pathogenesis of SLE and its correlation with disease activity.

Financial support and sponsorship

Nil.

Conflicts of interest

None declared.



 
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Shi ZR, Tan GZ, Meng Z, Yu M, Li KW, Yin J et al. Association of anti-acidic ribosomal protein P0 and anti-galectin 3 antibodies with the development of skin lesions in systemic lupus erythematosus. Arthritis Rheumatol 2015; 67:193–203.  Back to cited text no. 30
    
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    Tables

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



 

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