• Users Online: 330
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 45  |  Issue : 1  |  Page : 25-33

Correlation of serum interleukin-10 level with disease activity and severity in systemic lupus erythematosus


1 Department of Rheumatology and Rehabilitation, Faculty of Medicine, Beni Suef University, Beni Suef, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Beni Suef University, Beni Suef, Egypt
3 Department of Internal Medicine Department, Beni Suef University, Beni Suef, Egypt

Date of Submission19-Mar-2017
Date of Acceptance30-Jul-2017
Date of Web Publication9-Jan-2018

Correspondence Address:
Mervat I Abd Elazeem
1 Elgeesh Street, Elsaa Square, Elminia, 71111
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/err.err_15_17

Rights and Permissions
  Abstract 


Background Systemic lupus erythematosus (SLE, lupus) is a syndrome of multifactorial etiology, characterized by widespread inflammation, most commonly affecting women during the childbearing years. Virtually, every organ and/or system of the body may be involved. Interleukin-10 (IL-10) production is increased in SLE.
Objective The aim of the study was to assess serum levels of IL-10 in SLE patients and their relationship with disease activity and severity parameters.
Patients and methods Totally, 50 patients with SLE and 20 healthy controls were investigated in this study diagnosed according to Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE. Clinical assessment of the disease activity was performed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. Assessment of SLE disease severity was carried out using the SLICC/American College of Rheumatology Damage Index and laboratory parameters, including erythrocyte sedimentation rate, C-reactive protein (CRP), 24 h urinary proteins, anti-dsDNA antibodies, complement 3, and complement 4 levels. The serum IL-10 levels were determined using enzyme-linked immune sorbent assay technique.
Results The serum IL-10 levels were significantly higher in SLE patients (mean: 23.07±33.19 pg/ml) compared with the controls (0.52±0.86 pg/ml, P=0.000*). The increase in serum levels IL-10 significantly correlated with the SLEDAI scores (P=0.016*) and CRP (P=0.042*) in the studied patients. There were no significant correlations between IL-10 and SLICC, age, disease duration, erythrocyte sedimentation rate, 24 h urinary protein, anti-DNA, and complement 3–complement 4 (P=0.735; r=0.05, P=0.890, P=0.521, P=0.529; r=0.09, P=0.430; r=0.11, P=0.263; r=0.16, P=0.195; r=0.19, respectively).
There was no significant difference between mean IL-10 levels in different classes of lupus nephritis (P=0.702).
Conclusion The circulating IL-10 concentrations were significantly elevated in SLE patients and correlated with the SLEDAI score and CRP.

Keywords: enzyme-linked immune sorbent assay, interleukin-10, systemic lupus erythematosus, systemic lupus erythematosus disease activity index


How to cite this article:
Abd Elazeem MI, Mohammed RA, Abdallah NH. Correlation of serum interleukin-10 level with disease activity and severity in systemic lupus erythematosus. Egypt Rheumatol Rehabil 2018;45:25-33

How to cite this URL:
Abd Elazeem MI, Mohammed RA, Abdallah NH. Correlation of serum interleukin-10 level with disease activity and severity in systemic lupus erythematosus. Egypt Rheumatol Rehabil [serial online] 2018 [cited 2018 Jan 16];45:25-33. Available from: http://www.err.eg.net/text.asp?2018/45/1/25/222629




  Introduction Top


Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by B lymphocyte hyperactivity, production of autoantibodies directed against double-stranded DNA, and dysfunction of antigen presenting cells and T lymphocytes. Increased production and decreased clearance of immune complexes lead to immune complex deposition in tissue and damage to multiple organ systems. Interleukin-10 (IL-10) has the ability to induce autoantibody production by B lymphocytes, suggesting that IL-10 plays an important role in the pathogenesis of SLE [1]. The great sources of IL-10 in patients with SLE are B-cells and monocytes. IL-10 overproduction by B lymphocytes and monocytes was described for the first time by Lorente et al. [2].

The IL-10 cytokine is required for regulating immune functions by motivating the widespread suppression of immune responses through its pleiotropic effects. The Interleukin 10 (IL-10) cytokine is required for regulating immune functions by promoting the widespread suppression of immune responses through its pleiotropic effects and the autocrine/ paracrine capabilities of IL-10 by direct binding to leukocytes and function of this cytokine. IL-10 secretion from CD4+CD25+FoxP3+regulatory cells (Tregs), macrophages, and other leukocytes, followed by subsequent binding to IL-10 receptors on macrophages and dendritic cells (DCs), has been linked to decreased antigen presentation and increased T-cell anergy [3].

Immune cells express IL-10 with T-cells and B-cells, natural killer cells, mast cells, eosinophils, DCs, and monocytes/macrophages as major sources. IL-10 modulates T-cell responses through the inhibition of major histocompatibility complex class II expression, limited costimulation, and decreased proinflammatory cytokine expression from antigen presenting cells. Conversely, IL-10 promotes B-cell differentiation, proliferation, survival, and antibody production. Thus, IL-10 has been implicated in the pathophysiology of autoimmune disorders [1]. In early lupus, IL-10 was observed to play a downregulatory role, whereas at later phases of disease excessive production of IL-10 might result in enhanced autoantibody production and subsequent formation of pathogenic autoantibody–antigen complexes, as it has been illustrated in in-vitro studies that anti-IL-10 antibodies could markedly inhibit immunoglobulin production by SLE peripheral blood mononuclear cells (PBMC), which confirmed the role of IL-10 in mediating autoantibody production [4]. Yin et al. [5]. found that the serum IL-10 was significantly higher in SLE patients compared with controls. Furthermore, such an increase in the level of IL-10 showed a highly significant positive correlation with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores in the studied patients. Abnormal production of autoantibodies by B lymphocytes in patients with SLE is IL-10 dependent, and all related studies found that there is a positive correlation of serum IL-10 levels with disease activity [6]. This study aimed to assess serum levels of IL-10 in SLE and their relationship with disease activity and severity, as it might supply future views for targeted therapeutic strategies in SLE.


  Patients and methods Top


This study was conducted on 50 clinically diagnosed SLE patients (44 female and six male) who were selected from the Rheumatology and Rehabilitation Department of Beni Suef University hospital from June 2015 to April 2016 and diagnosed according to Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE [7]. Twenty healthy adults served as a control group; consent was taken from all individuals in this study. The study population was subjected to the following clinical and investigational workup: full history taking including age, sex, disease duration, and swollen and tender joint counts of the patients; chest radiography; and echocardiography. Clinical assessment of the disease activity was performed using the SLEDAI score [8]. An SLEDAI score of more than 6 was considered active disease. Laboratory workup included routine laboratory survey with complete blood picture [9] and erythrocyte sedimentation rate (ESR), which was expressed in mm/h [10]. The C-reactive protein (CRP) concentration was determined using immune nephelometry methods; concentrations of 6 mg/l were considered positive for CRP [11]. The serum levels of complement 3 (C3) and complement 4 (C4) were quantitatively measured in all samples by means of immune turbidimetry with the Turbid Time System according to the manufacturer’s instructions and expressed in terms of mg/dl [12]. Antinuclear antibody (ANA) [13] and antibodies to double-stranded DNA (anti-DNA) were measured using indirect immunofluorescence [14]. Anticardiolipin and lupus anticoagulant antibodies were measured. Blood samples from SLE patients and controls were centrifuged and sera were obtained for immediate routine laboratory workup. The remaining sera were stored frozen in aliquots at −20°C for the subsequent assays; urine analysis and 24 h urinary protein estimation were performed [15]. Renal biopsy was performed if indicated and classified according to the classification of lupus nephritis by the International Society of Nephrology/Renal Pathology Society [16]. Determination of serum IL-10 was performed using ELISA kits (Biosource International Inc.) following the manufacturers’ instructions; the samples, standard, and controls were added to wells, followed by the incubation buffer. After incubation, biotin-conjugated anti-IL-10 antibody was added to each well. After 2 h of incubation, streptavidin–HRP working conjugate was added; finally, chromogen was added, followed by the stop solution, and then absorbance was read at 450 nm. The normal values for serum IL-10 ranged between 7.8 and 500 pg/ml.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Statistical methods

For statistical analysis, statistical package for the social sciences software version 20 (SPSS Inc., Chicago, Illinois, USA) was used.

The following tests were used:
  1. Descriptive analysis of the results in the form of percentage distribution for qualitative data and minimum, maximum, mean and SD calculation for quantitative data.
  2. Cross tabulation test for comparison between percentage values.
  3. Student’s t-test for comparison between mean of two groups with a normal distribution.
  4. The Mann–Whitney or Kruskall–Wallis test was used to compare the mean of variables that did not have a normal distribution.
  5. The Correlation coefficient (r): Pearson’s correlation test was used to detect whether change in one variable is accompanied by a corresponding change in the other variable. A significant correlation may be positive, indicating that the change in the two variables is in the same direction or negative, indicating that the change in the two variables is in the opposite direction; the sign of the correlation coefficient (+, −) defines the direction of the relationship, either positive or negative and ‘r’ represents the correlation coefficient.


P value of greater than 0.05 was considered nonsignificant; P value of less than 0.05 was considered significant; P value of less than 0.01 was considered highly significant.


  Results Top


The present study was conducted on 50 SLE patients and 20 age-matched and sex-matched healthy controls.

Among the 50 SLE cases, there were 44 (88%) female and six (12%) male cases. As regards the age, it ranged from 21 to 52 years with a mean value of 27.48±9.58. As for the control group, there were 15 (77.3%) female and five (22.7%) male participants with a mean age of 25.90±4.57 years. As regards the disease duration, it ranged from 1 to 72 months with a mean value of 25.76±17.98 months ([Table 1]).
Table 1 Demographic data of systemic lupus erythematosus cases and controls

Click here to view


The clinical and descriptive data of SLE patients are shown in [Table 2].
Table 2 Clinical data of systemic lupus erythematosus patients

Click here to view


The number of patients with renal disorders was 33 (66%) patients [mesangial, four (12.1%) patients; focal proliferative, 12 (36.4%) patients; diffuse proliferative, six (18.2%) patients; membranoproliferative, six (18.2%) patients; mesangioproliferative, four (12.1%) patients; and membranous, one (3.0%) patient] ([Figure 1]).
Figure 1 Renal disorders in lupus nephritis patients.

Click here to view


As regards the SLEDAI score in all SLE cases, it ranged from 0 to 48 with a mean of 13.50±10.43, whereas the SLICC score ranged from 0 to 10 with a mean of 1.68±1.73 ([Table 3]).
Table 3 The systemic lupus erythematosus disease activity index, systemic lupus international collaborating clinics scores in all systemic lupus erythematosus cases

Click here to view


The first hour ESR ranged from 8 to 180 mm/h with a mean value of 67.98±41.66 mm/h.

As regards the CRP, the number of patients with negative CRP was 35 (70%), whereas the number of patients with positive CRP was 15 (30%), which ranged from 3 to 96 mg/l with a mean of 25.48±28.119 mg/l.

As regards the complete blood picture, the hemoglobin level ranged from 6 to 15 g/dl with a mean of 10.30±2.06 g/dl. The white blood cell count ranged from 2 to 20 (103/μl) with a mean of 6.32±3.24 (103/μl). The platelet count ranged from 60 to 477 (103/μl) with a mean of 259.18±98.31 (103/μl). The 24 h urinary protein level ranged from 85 to 3500 mg/dl with a mean of 1097.40±1038.17 mg/dl.

All patients had a positive ANA (100%), 31 (62%) patients had positive anti-dsDNA, and 19 (38%) patients had negative anti-dsDNA.

As regards the C3 and C4 levels, the number of patients with consumed C3 and C4 was 23 (46%), whereas the number of patients with normal C3 and C4 was 27 (54%).

The number of patients with positive anticardiolipin was four (8%), and the number of patients with positive lupus anticoagulant was three (6%).

There was a highly statistically significant difference (P=0.000) on comparing results of serum IL-10 in cases and controls. The mean serum IL-10 levels was 23.07±33.19 pg/ml in the patient group and it was 0.52±0.86 in the healthy control group.

There was no significant difference between mean IL-10 levels in male patients compared with female patients (P=0.788) ([Figure 2]).
Figure 2 The mean serum interleukin-10 (IL-10) level in male and female participants.

Click here to view


There was no statistically significant relation found on correlating serum IL-10 with age of patients (P=0.890). Correlation coefficient was 0.02, which revealed a weak positive correlation. There was no statistically significant relation found on correlating serum IL-10 with disease duration (P=0.521). Correlation coefficient was 0.09.

There was no statistically significant difference on comparing IL-10 levels in SLE patients. According to the disease activity status based on the SLEDAI scoring system, IL-10 levels were higher in the active group (mean: 24.22±32.79 pg/ml) compared with the nonactive group (17.06±36.97 pg/ml) ([Table 4]).
Table 4 Comparing results of serum interleukin-10 level and Systemic Lupus Erythematosus Disease Activity Index score in systemic lupus erythematosus patients

Click here to view


There was a significant correlation between serum IL-10 and the SLEDAI score in all SLE patients (P=0.016; r=0.34) ([Table 5]).
Table 5 Correlation of Systemic Lupus Erythematosus Disease Activity Index score and Systemic Lupus International Collaborating Clinics score with serum interleukin-10 in all patients

Click here to view


SLICC/American College of Rheumatology (ACR) score for cumulative organ damage was correlated with IL-10 in all SLE patients to determine whether IL-10 has a role in SLE organ damage. There was no statistical correlation detected on correlating SLICC/ACR score with IL-10 in SLE patients (P=0.735; r=0.05) ([Table 5]).

On comparing results of serum IL-10 level in lupus nephritis and nonlupus nephritis patients, the mean serum level of IL-10 was 20.90±22.48 in lupus nephritis, whereas it was 27.28±48.32 in nonlupus nephritis. There was no significant difference between mean IL-10 levels in lupus nephritis and nonlupus nephritis (P=0.743).

There was no significant difference between mean IL-10 levels in different classes of lupus nephritis (P=0.702). The mean serum level of IL-10 was 25.85±12.32 in mesangial, 25.70±26.72 in focal proliferative, 15.23±22.13 in diffuse proliferative, 18.55±26.47 in membranoproliferative, 16.77±19.04 in mesangioproliferative, and 8.30±0 in membranous class.

There was a statistically significant difference on comparing IL-10 levels in the CRP-positive and CRP-negative groups. The mean serum IL-10 level was 38.02±47.36 pg/ml in the CRP-positive group was and was 16.66±22.88 in the CRP-negative group (P=0.043) ([Figure 3]). Moreover, correlation analysis between IL-10 and CRP was significant (r=0.29; P=0.042*) ([Figure 4]).
Figure 3 The mean serum interleukin-10 (IL-10) level in the C-reactive protein (CRP)-positive and CRP-negative groups.

Click here to view
Figure 4 Correlation of serum interleukin-10 (IL-10) in all patients with C-reactive protein (CRP).

Click here to view


There was no statistically significant relation found on correlating serum IL-10 with ESR (P=0.529). Correlation coefficient was 0.09, which revealed a weak positive correlation. There was no statistically significant relation found on correlating serum IL-10 with 24 h urinary protein (P=0.430). Correlation coefficient was 0.13, which revealed a weak positive correlation.

There was no statistically significant relation found on correlating serum IL-10 with C3 (P=0.195). Correlation coefficient was 0.19, which revealed a weak positive correlation.

There was no statistically significant relation found on correlating serum IL-10 with anti-DNA (P=0.263). Correlation coefficient was 0.16, which revealed a weak positive correlation. There was no statistically significant relation found on correlating serum IL-10 with ANA (P). Correlation coefficient was negative ([Table 6]).
Table 6 Correlation of serum interleukin-10 with laboratory finding in all patients

Click here to view



  Discussion Top


SLE is an autoimmune disease with variations in incidence, prevalence, disease activity, and prognosis based on race and ethnicity [17]. SLE is a chronic systemic disease with variable clinical presentation. The exact pathological mechanisms of SLE remains elusive, and the cause of SLE is multifactorial, involving genes, sex hormones, and environmental factors, including sunlight, drugs, and infections [18].

Immune complexes that are produced in SLE acting through Fc γ receptor II stimulate IL-10 production from PBMC, thus perpetuating the pathological cycle. Rönnelid et al. [19] showed a significant increase in IL-10 production in cell cultures incubated with SLE sera, in comparison with cell cultures incubated with control sera. This effect gives a possible explanation for the enhanced production of IL-10 in patients with SLE, which leads to B-cell hyperactivity, autoantibody production, immune complex production, PBMC stimulation, and also production of IL-10. Stimulation of this cycle leads to increased deposition of immune complexes in tissues and SLE-related pathology [19].

The current research aimed to assess the relationship between SLE disease activity in a population of Egyptian patients in terms of the SLEDAI score and one of the most pathogenetically significant cytokines that have attracted researchers, IL-10. In addition, the study tried to explore the possible influence of the serologic profile and the results of the inflammatory biomarkers on the level of this cytokine. The present study included 50 SLE patients who were compared with 20 age-matched and sex-matched healthy unrelated controls. Both the patient and control groups were subjected for the analysis of IL-10 using enzyme-linked immune sorbent assay technique.

This study included 70 participants, and 50 of them were suffering from SLE. An overall 88% of SLE patients were female and 12% were male. This finding indicates that female sex is considered as one of the predisposing factors of the disease and that hormones share through unknown mechanisms to increase the prevalence of SLE among women. The X chromosome may share in increasing the severity of the disease, as the gene known to contribute to the pathogenesis of SLE is CD40, which is placed on chromosome X [20]. In the current case–control study, there was a highly statistically significant difference on comparing IL-10 levels in SLE patients and healthy controls. The mean serum IL-10 level was 23.07±33.19 pg/ml in the patient group and it was 0.52±0.86 in healthy controls (P=0.000).

The overproduced IL-10 in SLE patients may be due to B-cells and monocytes [21]. Moreover, B-cell secretion of IL-10 could regulate DCs and T-cell function to motivate Th2 cell deviation of the immune response [22]. So, the increased excretion of IL-10 may be due to an increasing number of the earlier peripheral B-cell abnormalities including plasma cell spread [23].

In accordance with the results of the current study, Sahar et al. [24] indicated that in SLE patients the mean IL-10 levels was 120±27.2 pg/ml compared with a mean of 76±14.2 pg/ml in healthy controls (P=0.001). In addition, our results on the significant difference in IL-10 level detected between SLE patients and healthy controls were in agreement with the results of the studies conducted by Liviu et al. [25], Zhihua et al. [26], Yang et al. [27], and Ahmad et al. [28].

However, contrary to our results, Dhir et al. [29] and Chen et al. [30] found that there was no difference in serum IL-10 level between patients and controls. These conflicts may have arised probably from many potential factors such as sample size, patients with different demographics, clinical characteristics, or types of therapy. In addition, in some indices measured for SLE activity, qualitative data with high heterogenecity between studies can also contribute to this discordance.

In the current case–control study, we compared the IL-10 levels in SLE patients according to the disease activity status based on the SLEDAI scoring system. IL-10 levels were higher in the active group (mean: 24.22±32.79 pg/ml) compared with the nonactive group (17.06±36.97 pg/ml); however, the results did not reach statistical significance (P=0.072). However, correlation analysis between IL-10 and SLEDAI was statistically significant (r=0.34, P=0.016*).

In accordance with the results of the current study, Ahmad et al. [28] found that positive correlation between IL-10 levels and SLEDAI was highly significant (r=0.503, P<0.001).

Similarly, Yang et al. [27] indicated that IL-10 level was higher in active patients than in nonactive ones, and serum IL-10 level was correlated with SLEDAI.

In addition, several research groups [31],[32],[33],[34] had reported that the serum IL-10 level was correlated with SLEDAI. However, contrary to our results, on evaluating the correlation between the two variables, they detected a significant negative correlation. These results were contradicted by Lorente et al. [35] and Arora et al. [36]; such discrepancy might be attributed to the difference in the assessment technique as the current study measured IL-10 in the sera of patients, whereas in the study by Lorente and colleagues the authors studied its concentration in peripheral mononuclear cells cultures after 24 h.

In our study, there was a statistically significant difference on comparing IL-10 levels in the CRP-positive and CRP-negative groups. The mean serum IL-10 level was 38.02±47.36 pg/ml in the CRP-positive and 16.66±22.88) in CRP-negative groups (P=0.043). Moreover, correlation analysis between IL-10 and CRP was significant (r=0.29, P=0.042*).

In accordance with the results of the current study, Zhihua et al. [26] and Sahar et al. [24] had found that there was a significant positive correlation between IL-10 and CRP (r=0.373, P=0.001). In contrast, Lacki et al. [37] and Capper et al. [38] had found that there was no correlation between IL-10 and serum level of CRP.

Our study had found an increase in IL-10 serum in lupus nephritis patients in comparison with those without renal involvement (without statistical significance). The mean serum IL-10 level was 20.90±22.48 in lupus nephritis and was 27.28±48.32 in nonlupus nephritis (P=0.743).

There were no significant differences in serum level of IL-10 among different pathological classes (P=0.702). The mean serum level of IL-10 was 25.85±12.32 in mesangial, 25.70±26.72 in focal proliferative, 15.23±22.13 in diffuse proliferative, 18.55±26.47 in membranoproliferative, 16.77±19.04 in mesangioproliferative, and 8.30±0 in membranous.

In accordance with the results of the current study, Sikka et al. [39] and Sameh et al. [40] had found that there was no difference on comparing IL-10 levels in lupus nephritis patients with those without renal involvement.

There was no statistically significant difference detected on correlating IL-10 with anti-DNA (P=0.263).In contrast, Houssiau et al. [41], Park et al. [32], and El-Sayed et al. [42] in their study found that IL-10 positively correlated with anti-DNA. However, the reason for the discrepancy between our results and this study remains unexplained.

There was no statistically significant difference detected on correlating IL-10 with C3 and C4 (P=0.195). In accordance with the results of the current study, Sahar et al. [24] found a significant positive correlation between serum IL-10 and C4 (r=0.741, P<0.05).

In contrast with the results of the current study, Ishida et al. [31], Chun et al. [33], and Zhihua et al. [26] found that IL-10 negatively correlated with C3 and C4. Ma et al. [43] found that IL-10 negatively correlated with C3. Moreover, Sahar et al. [24] found no significant correlations between serum IL-10 and C3 levels (r=0.25, P>0.05).

There was no statistically significant difference detected on correlating IL-10 with ESR. In accordance with the results of the current study, Sahar et al. [24] found that there were no significant correlations between serum IL-10 and ESR (r=−0.208, P>0.05). Moreover, Ma et al. [43] in their study found that IL-10 negatively correlated with ESR. In contrast, a significant correlation was found between serum IL-10 and ESR in the studies of Capper et al. [38] and Zhihua et al. [26].

In the current study, SLICC/ACR score for cumulative organ damage was correlated with IL-10 in all SLE patients to determine whether IL-10 has a role in SLE organ damage. There was no statistically significant correlation detected on correlating SLICC/ACR score with IL-10 in SLE patients (P=0.735, r=0.05).

In accordance with the results of the current study, Eoghan et al. [44] in their study found that there was no statistical significance detected on correlating SLICC/ACR score with IL-10 (P=0.072).

In accordance with the therapeutic effect of anti-IL-10 antibodies, the continuous administration of recombinant IL-10 increased disease activity. Similarly, in a small, uncontrolled, open label study including patients with mild disease, anti-IL-10 monoclonal antibody improved skin lesions, joint symptoms, and the SLEDAI [45].

Therefore, the study concluded that the circulating IL-10 concentrations were significantly elevated in SLE patients and correlated with the SLEDAI score and CRP and it might be used as a serum marker to evaluate disease activity. Contribution of our studied cytokine might supply future ideas for targeted therapeutic strategies in SLE.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Peng H, Wang W, Zhou M, Li R, Pan HF, Ye DQ. Role of interleukin-10 and interleukin-10 receptor in systemic lupus erythematosus. Clin Rheumatol 2013; 32:1255–1266.  Back to cited text no. 1
    
2.
Lorente L, Richaud PY, Wijdenes J, Alcocer-Varela J, Maillot MC et al. Spontaneous production of interleukin-10 by B lymphocytes and monocytes in systemic lupus erythematosus. Eur Cytokine Netw 1993; 4:421–427.  Back to cited text no. 2
    
3.
Shalev I, Schmelzle M, Robson SC, Levy G. Making sense of regulatory T cell suppressive function. Semin Immunol 2011; 23:282–292.  Back to cited text no. 3
    
4.
Yin Z, Bahtiyar G, Zhang N, Liu L, Zhu P et al. IL-10 regulates murine lupus. J Immunol 2002; 169:2148–2155.  Back to cited text no. 4
    
5.
Yin Z, Huang J, He W, Cao Z, Luo X, Zhang C. Serum level of eight cytokines in Han Chinese patients with systemic lupus erythematosus using multiplex fluorescent microsphere method. Centr Eur J Immunol 2014; 39:228–235.  Back to cited text no. 5
    
6.
Da Silva HD, da Silva AP, da Silva HA, Asano NM, Maia Mde M, de Souza PR. Interferon gamma and interleukin 10 polymorphisms in Brazilian patients with systemic lupus erythematosus. Mol Biol Rep 2014; 41:2493–2500.  Back to cited text no. 6
    
7.
Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR. Derivation and validation of Systemic Lupus International Collaborating Clinics Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheum 2012; 64:2677–2686.  Back to cited text no. 7
    
8.
Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002; 29:288–291.  Back to cited text no. 8
    
9.
Newland J, Goldman L, Ausiello D. The peripheral blood smear. In: Wyngaarden JB, Smith LH Jr, Claude Bennett J, editors. Cecil medicine. 23rd ed. Philadelphia, PA, USA: Saunders Elsevier; 2007. 161:1212–1216.  Back to cited text no. 9
    
10.
Dacie V, Lewis M. Practicle heamatology Vol. 12. 6th ed. Edinburgh, London: Churchil Livingstone; 1984. 4220.  Back to cited text no. 10
    
11.
Karlson D, Elizabeth W, Paul M, Ridker M, Maher N, JoAnn E, Manson M. C-reactive protein in the prediction of rheumatoid arthritis in women. Arch Intern Med 2006; 166:2490–2494.  Back to cited text no. 11
    
12.
De Bruijn MH, Fey GH. Human complement component C3: cDNA coding sequence and derived primary structure. Proc Natl Acad Sci USA 1985; 82:708–712.  Back to cited text no. 12
    
13.
Aitcheston C, Tan C. Antinuclear antibody in scientific basis of rheumatology. In: Panayi GS (editor). Edinburgh, London, Melbourne and New York: Churil Livingstone; 1982. 87.  Back to cited text no. 13
    
14.
Okamura M, Kanayama Y, Amastu K, Negoro N, Kohda S, Takeda T et al. Significance of enzyme linked immune-sorbent assay (ELISA) for antibodies to double stranded and single stranded DNA in patients with lupus nephritis: correlation with severity of renal histology. Ann Rheum Dis 1993; 52:14–20.  Back to cited text no. 14
    
15.
Bazari H. Approach to the patient with renal disease. In: Goldman L, Ausiello D, editors. Cecil medicine. 23rd ed. Philadelphia, PA, USA: Saunders Elsevier; 2007. 115.  Back to cited text no. 15
    
16.
Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 2004; 65:521–530.  Back to cited text no. 16
    
17.
Mok CC, Yap DY, Navarra SV, Liu ZH, Zhao MH, Lu L. Asian Lupus Nephritis Network (ALNN). Overview of lupus nephritis management guidelines and perspective from Asia. Nephrology (Carlton) 2014; 19:11–20.  Back to cited text no. 17
    
18.
Tiffin N, Adeyemo A, Okpechi I. A diverse array of genetic factors contribute to the pathogenesis of systemic lupus erythematosus. Orphanet J Rare Dis 2013; 8:2.  Back to cited text no. 18
    
19.
Rönnelid J, Tejde A, Mathsson L, Nilsson-Ekdahl K, Nilsson B. Immune complexes from SLE sera induce IL10 production from normal peripheral blood mononuclear cells by an FcgRII dependent mechanism: implications for a possible vicious cycle maintaining B cell hyperactivity in SLE. Ann Rheum Dis 2003; 62:37–42.  Back to cited text no. 19
    
20.
Tsokos GC. Mechanisms of diseases, systemic lupus erythematosus. N Engl J Med 2011; 365:2110–2121.  Back to cited text no. 20
    
21.
Hondowicz BD, Alexander ST, Quinn WJ, Pagán AJ, Metzgar MH, Cancro MP. The role of BLyS/BLyS receptors in anti-chromatin B cell regulation. Int Immunol 2007; 19:465–475.  Back to cited text no. 21
    
22.
Moulin V, Andris F, Thielemans K, Maliszewski C, Urbain J, Moser M. B lymphocytes regulate dendritic cell (DC) function in vivo: increased interleukin 12 production by DCs from B cell-deficient mice results in T helper cell type 1 deviation. J Exp Med 2000; 192:475–482.  Back to cited text no. 22
    
23.
Jacobi AM, Odendahl M, Reiter K, Bruns A, Burmester GR et al. Correlation between circulating CD27 high plasma cells and disease activity in patients with systemic lupus erythematosus. Arthritis Rheum 2003; 48:1332–1342.  Back to cited text no. 23
    
24.
Sahar AF, Reem HA, Hanan S, Mohmad A. Serum interleukin-18 and interleukin-10 levels in systemic lupus erythematosus: correlation with SLEDAI score and disease activity parameters. Egypt Rheumatol Rehabil 2014; 41:160–166.  Back to cited text no. 24
    
25.
Liviu G, Vakkalanka RK, Elkon KB, Crow MK. Interleukin-10 promotes activation-induced cell death of SLE lymphocytes mediated by Fas Ligand. J Clin Invest 1997; 100:2622–2633.  Back to cited text no. 25
    
26.
Yin Z, Huang J, He W, Cao Z, Luo X, Zhang C. Serum level of eight cytokines in Han Chinese patients with systemic lupus erythematosus using multiplex fluorescent microsphere. Centr Eur J Immunol 2014; 39:228–235.  Back to cited text no. 26
    
27.
Yang X, Sun B, Wang H, Yin C, Wang X et al. Increased serum IL-10 in lupus patients promotes apoptosis of T cell subsets via the caspase 8 pathway initiated by Fas signaling. J Biomed Res 2015; 29:232–240.  Back to cited text no. 27
    
28.
Ahmad AE, Kamal FM, Nisreen EE, Mai HR. Effects of interleukin-10 gene polymorphism on clinical diversity and activity of systemic lupus erythematosus. Egypt Rheumatol Rehabil 2015; 42:49–54.  Back to cited text no. 28
    
29.
Dhir V, Singh AP, Aggarwal A, Naik S, Misra R. Increased T-lymphocyte apoptosis in lupus correlates with disease activity and may be responsible for reduced T-cell frequency: a cross-sectional and longitudinal study. Lupus 2009; 18:785–791.  Back to cited text no. 29
    
30.
Chen J, Shen B, Jiang Y, Jun L, Zhu M, Chen B. Analysis of immunoglobulin-like transcripts (ILTs) in lymphocytes with sHLA-G and IL10 from SLE patients. Clin Exp Med 2013; 13:135–142.  Back to cited text no. 30
    
31.
Ishida H, Muchamuel T, Sakaguchi S, Andrade S, Menon S, Howard M. Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice. J Exp Med 1994; 179:305–310.  Back to cited text no. 31
    
32.
Park YB, Lee SK, Kim DS, Lee J, Lee CH, Song CH. Elevated interleukin-10 levels correlated with disease activity in systemic lupus erythematosus. Clin Exp Rheumatol 1998; 16:283–288.  Back to cited text no. 32
    
33.
Chun HY, Chung JW, Kim HA, Yun JM, Jeon JY, Ye YM. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol 2007; 27:461–466.  Back to cited text no. 33
    
34.
Koenig KF, Groeschi I, Pesickova SS, Tesar V, Eisenberger U, Trendelenburg M. Serum cytokine profile in patients with active lupus nephritis. Cytokine 2012; 60:410–416.  Back to cited text no. 34
    
35.
Lorente L, Richaud PY, Garcia PC, Claret E, Jakez OJ et al. Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus. Arthritis Rheum 2000; 43:1790–1800.  Back to cited text no. 35
    
36.
Arora V, Verma J, Marwah V, Kumar A, Anand D, Das N. Cytokine imbalance in systemic lupus erythematosus: a study on northern Indian subjects. Lupus 2012; 21:596–603.  Back to cited text no. 36
    
37.
Lacki JK, Samborski W, Mackiewicz SH. Interleukin-10 and interleukin-6 in lupus erythematosus and rheumatoid arthritis, correlations with acute phase proteins. Clin Rheumatol 1997; 16:275–278.  Back to cited text no. 37
    
38.
Capper ER, Maskill JK, Gordon C, BlakemoreA IF. Interleukin (IL)-10, IL-1ra and IL-12 profiles in active and quiescent systemic lupus erythematosus: could longitudinal studies reveal patient subgroups of differing pathology. Clin Exp Immunol 2004; 138:348–356.  Back to cited text no. 38
    
39.
Sikka G, Miller KL, Steppan J, Pandey D, Jung SM, Fraser CD. Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age. Exp Gerontol 2013; 48:128–135.  Back to cited text no. 39
    
40.
Sameh AZ, Ghada K, Malak N. IL10 in lupus nephritis: detection and relationship with disease activity. Electron Physician 2015; 7:1680–1685.  Back to cited text no. 40
    
41.
Houssiau FA, Lefebvre C, Vanden Berghe M, Lambert M, Devogelaer JP, Renauld JC. Serum interleukin 10 titers in systemic lupus erythematosus reflect disease activity. Lupus 1995; 4:393–395.  Back to cited text no. 41
    
42.
El-Sayed M, Nofal E, Al Mokadem S, Al Makhzangy I, Gaballah H, Hossneia A. Correlative study of serum Th1/Th2 cytokines levels in patients with systemic lupus erythematosus with SLEDAI. Egypt Dermatol Online J 2008; 4:3.  Back to cited text no. 42
    
43.
Ma L, Zhao P, Jiang Z, Shan Y, Jiang Y. Imbalance of different types of CD4+forkhead box protein 3 (FoxP3)+ T cells in patients with new-onset systemic lupus erythematosus. Clin Exp Immunol 2013; 174:345–355.  Back to cited text no. 43
    
44.
Eoghan MM, Siobha N, Ruth ZL, Gaye C, Michele F, Donnelly S. The association of cytokines with disease activity and damage scores in systemic lupus erythematosus patients. Rheumatology (Oxford) 2014; 53:1586–1594.  Back to cited text no. 44
    
45.
Ravirajan CT, Wang Y, Matis LA, Papadaki L, Griffiths MH, Latchman DS. Effect of neutralizing antibodies to IL-10 and C5 on the renal damage caused by a pathogenic human anti-dsDNA antibody. Rheumatology (Oxford) 2004; 43:442–447.  Back to cited text no. 45
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

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



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and methods
Results
Discussion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed18    
    Printed0    
    Emailed0    
    PDF Downloaded9    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]