Analysis of CD95 and CCR7 expression on circulating CD4+ lymphocytes revealed disparate immunoregulatory potentials in systemic lupus erythematosus

Emerging data have implicated a critical role for CD4 in the pathogenesis of systemic lupus erythematosus (SLE). This study was designed to delineate the contribution of CD4⁺ T cells in the pathogenesis of SLE disease. Forty-four patients (3 male: 41 female) and 20 healthy volunteers (4 male: 16 female) were included in the study. CD4⁺ lymphocytes analysis was done using three-color flow cytometry with antibodies against human-CD95, a prototype cell death receptor, and the chemokine receptor-7 (CCR7) after gating for lymphocytes based on the forward and side scatter. Serum levels of IL-6, IL-12, IL-17, TNF-α and IL-10 cytokines were assayed using ELISA. Disease activity was assessed using the SLE disease activity index (SLEDAI). Based on the expression of CCR7 and CD95, CD4⁺ lymphocytes were subdivided into three particular subsets; CD4⁺CD95⁺CCR7⁺ cells, CD4⁺CD95⁻CCR7⁺ cells and CD4⁺CD95⁺CCR7⁻ cells. Percentage of CD4⁺CD95⁺CCR7⁺ cell subset was significantly higher in patients with SLE with active disease (SLEDAI > 6) and inactive (SLEDAI < 6) as compared with controls (P = 0.005), and it showed a significant positive correlation with ANA titer (P = 0.01), and a negative correlation with WBCs count (P = 0.001). CD4⁺CD95⁺CCR7⁻ cell subset was significantly higher in active SLE patients in comparison to patients with inactive disease and controls (P = 0.05, P = 0.005 respectively), and it correlates positively with SLEDAI, IL-6 and IL-17 levels (P = 0.001, 0.05, 0.01 respectively), and negatively with blood WBCs counts (P = 0.001). The third CD4⁺CD95⁻CCR7⁺cell subset was found significantly lower in SLE patients compared with controls, and it was found negatively correlated with IL-10, IL-6, and IL-17. The results show that CD4⁺CD95⁺subset lacking expression of CCR7 is associated with cell mediated inflammatory response as manifested by its correlation with signs of inflammation, inflammatory cytokines and disease activity index. Whereas, CD4⁺CD95⁺CCR7⁺ correlate more with antibody immune responses as manifested by association with serum ANA. These data suggest disparate roles of these cell subsets in the pathophysiology of SLE. A better understanding of the characteristics of CD4 cell subsets may shed light on the pathogenesis of autoimmune diseases, particularly SLE.     

Soluble granzyme B and cytotoxic T lymphocyte activity in the pathogenesis of systemic lupus erythematosus

Activated cytotoxic T lymphocyte (CTL) mediated target cell death has been implicated in the development of systemic autoimmune disease like SLE. However, the role of soluble granzyme B and its relationship with CTL activity and disease activity is still unknown. In this study, we evaluated role of soluble granzyme B and cytotoxic T lymphocyte activity in SLE patients. The soluble granzyme B was measured in the serum by an enzyme-linked immunosorbent assay while cytotoxic T lymphocyte activity was measured by flow cytometry. The disease activity was determined by using SLE Disease Activity Index (SLEDAI) score. Cytotoxic T lymphocyte activity was increased and strongly associated with disease activity. The soluble granzyme B levels were higher in SLE patients and associated with various clinical features like reduced complement components; C3 & C4 and skin lesion. The soluble granzyme B levels were also sturdily related with severity of the disease. The findings of this study suggest that excessive secretion of soluble granzyme B and enhanced activity of cytotoxic T lymphocyte may play a vital role in the pathogenesis of SLE and organ damage. Also, evaluation of soluble granzyme B may be helpful in monitoring the clinical features associated with activated CTL in SLE.     

Central nervous system function in systemic lupus erythematosus

Autoantibodies to three eukaryotic 60S ribosomal phosphoproteins P0, P1 and P2 have been found in the sera of 10–20% of patients with systemic lupus erythematosus (SLE). These antibodies inhibit protein synthesis in vitro and when microinjected into cultured human fibroblasts. The three proteins share a common epitope contained within the carboxyl terminal 22 amino acids of each protein. Because a significant number of SLE patients have central nervous system disturbances with major behavioral disorders, the antiribosomal protein autoantibodies were measured in this subset of SLE individuals to determine whether or not there was an association. These antibodies are present in 90% of SLE patients who were diagnosed as having psychosis, secondary to the disease.Special issue dedicated to Dr. Sidney underfriend     

Predictors of clinical outcomes in patients with neuropsychiatric systemic lupus erythematosus

IntroductionNeuropsychiatric systemic lupus erythematosus (NPSLE), a serious organ disorder with a variety of symptoms, has diverse therapeutic outcomes because of the variability of NPSLE manifestations. A comprehensive association study of NPSLE among clinical and immunopathogenic aspects and outcomes has not been conducted.MethodsWe analyzed the laboratory data, NPSLE symptoms, and clinical outcomes at 1 yr post-treatment and the profiles of 27 cytokines, chemokines and growth factors in cerebrospinal fluid (CSF) samples using the Bio-Plex Human 27-plex panel from 28 NPSLE patients. Univariate and multivariable competing risks regression analyses were used to determine the predictive factors of clinical response. We also tried to predict the outcome of NPSLE by the 27 cytokines/chemokines/growth factors using a weighted-voting (WV) algorithm.ResultsOf the two males and 26 females (92.9%), 16 were non-responders at 1 yr post-treatment; in the final model, the independent predictors of non-responders were longer disease durations of SLE (odds ratio [OR]: 1.490, 95% confidence interval [CI]: 1.143–2.461, p = 0.0003) and patients with more than one NPSLE symptom types (OR: 15.14, 95% CI: 1.227–452.1, p = 0.0334). The pretreatment CSF interleukin (IL)-6, IL-10, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) levels were significantly higher in the non-responders (p = 0.0207, p = 0.0054, p = 0.0242 and p = 0.0077, respectively). We identified six “minimum predictive markers:” IL-10, TNF-α, IL-6, IFN-γ, IL-4 and IL-13 by a WV algorithm that showed the highest accuracy (70.83%) and highest Matthews correlation coefficient (54.23%).ConclusionsWe have devised a numerical prediction scoring system that was able to separate the non-responders from responders. The patients with longer disease durations of SLE and those with more than one NPSLE symptom types had poorer outcomes. Our findings may indicate both the importance of making a diagnosis at an earlier phase for better therapeutic response and the usefulness of measuring multiple cytokines to predict NPSLE therapeutic outcomes.     

系统性红斑狼疮与肠道菌群关系研究进展

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种慢性进行性自身免疫疾病,可累及全身多器官。SLE的发病机制不仅与遗传易感性有关,还与环境因素有关,其中肠道菌群紊乱引起了越来越多的关注。研究表明,肠道菌群是影响自身免疫性疾病发病率的环境因素。公认的机制包括异常的微生物移位、分子拟态以及局部和全身免疫的失调。因此,肠道菌群及其代谢物影响SLE的发生发展。本文将重点探讨肠道菌群与SLE的关系,以及菌群干预作为SLE防治的新策略,为进一步研究SLE的诊断和治疗提供新的思路。     

Abnormal Fas/FasL and caspase-3-mediated apoptotic signaling pathways of T lymphocyte subset in patients with systemic lupus erythematosus

OBJECTIVES: To explore the relationships between Fas-FasL-mediated signaling pathway and apoptosis disturbance of T lymphocyte subset in patients with SLE. METHODS: Flow cytometry was used to determine the percentage of apoptotic lymphocytes and necrotic lymphocytes by AnnexinV-FITC/PI double staining. Cell surface expression rates of Fas, FasL, and intracellular expression rates of activated caspase-3 were evaluated by two-color flow cytometry analysis in peripheral T lymphocyte subsets of SLE patients with inactive disease (n=22) and with active disease (n=17). The serum concentration of anti-nucleosome antibodies in SLE patients were assayed by ELISA immunoassay methods. Health volunteers (n=13) served as controls. RESULTS: The percentage of early apoptotic cells was enhanced in patients with active disease (P=0.001, vs. control) and in patients with inactive disease (P=0.004, vs. control). Compared with health control, the percentage of necrotic cells was significant higher in patients with active disease (P=0.001). The percentages of CD4(+)T cells expressing Fas (P=0.023, vs. control) and FasL (P=0.001, vs. control) were increased in patients with active disease. But there were no obvious differences of expression rates of Fas and FasL on T cell subset between two disease groups (P>0.05). In patients with active disease the percentage of CD4(+)T cells or CD8(+)T cells expressing intracellular activated caspase-3 significantly increased compared to inactive disease patients (P=0.018, P=0.027, respectively) and health controls (P=0.001, P=0.001, respectively). The serum concentration of anti-nucleosome antibodies was strikingly higher in patients with active disease (P=0.002, vs. patients with inactive disease; P=0.001, vs. control, respectively), however, the serum concentration of anti-nucleosome antibodies was not obviously different between patients with inactive disease and health control group (P=0.473). The percentage of apoptotic cells correlated with the serum concentration of anti-nucleosome antibodies in SLE patients (r(s)=0.350, P=0.031). CONCLUSIONS: Apoptosis of T lymphocyte subset in SLE patients increases. CD4(+)T cells are a state of active apoptosis. Fas/FasL-mediated apoptotic pathways are especially important for CD4(+)T cells undergoing apoptosis in SLE patients with active disease. Increased Fas expression results in a higher susceptibility to Fas-mediated apoptosis, which contributes to the increased levels of intracellular activated caspase-3 and accelerates apoptosis of T lymphocytes. The degree of lymphocytic apoptosis disturbance correlates with the level of anti-nucleosome antibodies in the circulation. Acceleration of lymphocytic apoptosis plays important roles in immune pathologic injury and immune regulation dysfunction.     

Roles of CD147 on T lymphocytes activation and MMP-9 secretion in systemic lupus erythematosus

The cellular and molecular mechanisms involved in many abnormalities described in Systemic Lupus Erythematosus (SLE) are still unclear. Some of these abnormalities referred to the hyperactivation of T lymphocytes and the enhanced secretion of MMP-9 by peripheral blood mononuclear cells (PBMCs). Therefore, in this paper we investigated the potential role of CD147 molecule in these abnormalities. Our results demonstrated that CD147 molecule is overexpressed on CD3+T lymphocytes from SLE patients when compared with CD3+T lymphocytes from healthy donors. Monoclonal anti-CD147 antibodies, MEM-M6/1 clone, were able to inhibit protein tyrosine phosphorylation only in CD3 x CD28 costimulated T lymphocytes from SLE patients. However, this monoclonal antibody was unable to inhibit the enhanced activity of MMP-9 secreted by SLE PBMCs.     

The abnormal apoptosis of T cell subsets and possible involvement of IL-10 in systemic lupus erythematosus

To study the apoptosis of lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients and the possible role of IL-10 in this apoptosis involved in the pathogenesis of SLE, three color fluorescence and flow cytometry were used to investigate the early apoptosis of lymphocyte subsets from freshly separated or cultured peripheral blood mononuclear cells (PBMCs). ELISA was employed to detect the levels of IL-10 in serum and the levels of sFas and sFasL in cultured PBMC supernatants, and the results of sFas and sFasL were confirmed by real-time PCR of Fas and FasL mRNA. The results showed that in cells from SLE patients, the apoptosis of CD3+, CD4+, and CD8+ T cells was distinctly increased, and the percentage of CD4+ cells and the CD4/CD8 ratio was significantly decreased, as compared with normal controls. The apoptosis of T lymphocytes cultured with SLE serum was markedly higher than that of cells cultured with control's serum. Blockade of interleukin-10 (IL-10) activation by an anti-IL-10 antibody reduced the SLE serum induced apoptosis of CD4+ and CD8+ T cells. The levels of sFas and sFasL in the culture supernatant and Fas and FasL mRNA expressions in cultured cells were significantly higher in the SLE serum-cultured groups, but decreased evidently in the presence of the anti-IL-10 antibody. Above findings suggested that SLE cells showed abnormally high apoptosis of T lymphocytes, especially of the CD4+ subpopulation, resulting in a decreased CD4/CD8 ratio. The high percentage of apoptotic T cells in SLE patients may be related to the high levels of IL-10 in SLE serum, as IL-10 may induce the abnormally activated T cells to trigger apoptosis via the Fas-FasL pathway.     

Identification of autoantibodies associated with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of antinuclear antibodies. We performed serological analysis of cDNA expression library (SEREX) to identify autoantibodies associated with SLE. The screening of three different cDNA expression libraries with pooled sera of patients with SLE yielded 11 independent clones that reacted with pooled sera of patients with SLE. In this screening, autoantibodies to poly(ADP-ribose) polymerase (PARP), U1snRNP, and galectin-3 were prevalent in the sera of patients with SLE (26/68, 25/68, 12/63, respectively). The frequency of autoantibody to PARP was significantly higher in SLE than that of healthy donors (0/76) (38.2% vs 0%, p<0.00001). The autoantibody to PARP was infrequently detected in the serum of patients with RA (1/50). However, autoantibody to PARP was not found in the sera of patients with other rheumatic diseases including Sjogren's syndrome (0/19), systemic sclerosis (0/18), and polymyositis/myositis (0/37). The frequency of autoantibody to human galectin-3 (12/63) was significantly higher in SLE than that of healthy donors (0/56) (19% vs 0%, p=0.0006). Autoantibody to galectin-3 was not found in the sera of patients with rheumatoid arthritis (0/50), Sjogren's syndrome (0/18), and systemic sclerosis (0/19). Interestingly, autoantibody to galectin-3 was also prevalent in the sera of patients with polymyositis/dermatomyositis (16/37, 43.2%). Further functional characterization of these autoantibodies would be necessary to determine their value as diagnostic markers or to define clinical subsets of patients with SLE. Statistical analysis revealed that the presence of autoantibody to PARP was inversely related with pleurisy, and the presence of autoantibody to galectin-3 related with renal disease.     

Changes of frequency and expression level of CD161 in CD8+ T cells and natural killer T cells in peripheral blood of patients with systemic lupus erythematosus

Immunologic abnormalities of natural killer (NK) cells and T cells play a role in the pathogenesis of systemic lupus erythematosus (SLE). CD161 is expressed on most of the NK cells and on some T cells. The quantities of CD161-expressing cells and expression levels of CD161 were analyzed in T cells and NK cells from patients with SLE compared with normal controls. The expression of CD161 on NK cells, NKT cells, CD4⁺ T cells, and CD8⁺ T cells in peripheral blood from patients with inactive SLE and active SLE, and from the normal controls group were determined using flow cytometry. The frequency and expression level of CD161 in the lymphocyte subsets and its relationship with the quantity of regulatory T cells, anti-double stranded DNA antibody, and the titer of antinuclear antibody were evaluated. Both the percentages of the CD161⁺ subpopulation and the mean fluorescence intensities (MFIs) of CD161 in CD8⁺ T cells and NKT cells decreased significantly in SLE patients compared with normal controls (P < .001). The CD161 expression in CD8⁺ T cells and NKT cells also decreased in the anti-dsDNA (+) group (P < .05). The counts of Treg cells were lower in SLE patients and were weakly correlated with the percentage of the CD161 subpopulation (r = 0.229, P = .016) and the MFIs of CD161 expression in CD8⁺ T cells (r = .232, P = .014). The frequencies and levels of CD161 expression on CD8⁺ T cells and NKT cells were reduced in SLE patients, suggesting that an abnormality of these cells was related to the pathogenesis of SLE.     

Oxidative stress and its biomarkers in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease whose etiology remains largely unknown. The uncontrolled oxidative stress in SLE contributes to functional oxidative modifications of cellular protein, lipid and DNA and consequences of oxidative modification play a crucial role in immunomodulation and trigger autoimmunity. Measurements of oxidative modified protein, lipid and DNA in biological samples from SLE patients may assist in the elucidation of the pathophysiological mechanisms of the oxidative stress-related damage, the prediction of disease prognosis and the selection of adequate treatment in the early stage of disease. Application of these biomarkers in disease may indicate the early effectiveness of the therapy. This review is intended to provide an overview of various reactive oxygen species (ROS) formed during the state of disease and their biomarkers linking with disease. The first part of the review presents biochemistry and pathophysiology of ROS and antioxidant system in disease. The second part of the review discusses the recent development of oxidative stress biomarkers that relates pathogenesis in SLE patients and animal model. Finally, this review also describes the reported clinical trials of antioxidant in the disease that have evaluated the efficacy of antioxidant in the management of disease with ongoing conventional therapy.     

系统性红斑狼疮患者血清中CD83与自身抗体的表达及其相互关系

目的：检测系统性红斑狼疮（systemic lupus erythematosus,SLE）患者血清中CD83（soluble CD 83,sCD 83）和多种自身抗体的表达水平,并探讨其相互关系。方法：ELISA检测患者可溶性CD 83和AnuA的表达,应用间接免疫荧光的方法检测抗cmDNA抗体,应用乳凝法检测血清中的DNP,采用胶体金标记和快速膜渗滤技术测定血清中的抗dsDNA抗体。结果：对照组患者血清中可溶性CD 83的表达为（0.26±0.10）ng/ml,实验组患者血清中可溶性CD 83的表达为（5.56±0.72）ng/ml。与对照组相比,实验组患者血清中可溶性CD 83的平均浓度明显升高。在抗dsDNA抗体阴性的51例系统性红斑狼疮患者中AnuA的阳性率明显高于抗DNP抗体和抗cmDNA抗体,同样在抗DNP抗体阴性的58例系统性红斑狼疮患者中AnuA的阳性率明显高于dsDNA抗体和抗cmDNA抗体。系统性红斑狼疮患者中可溶性CD83的水平（〈2.68 ng/ml）与各种自身抗体（抗dsDNA抗体、AnuA、抗DNP抗体和抗cmDNA抗体）水平的相关系数分别为（r=0.542,0.613,0.489和0.367）。具有高水平可溶性CD83的系统性红斑狼疮患者（≥2.68 ng/ml）,与各种自身抗体（抗dsDNA抗体,AnuA,抗DNP抗体和抗cmDNA抗体）水平的相关系数分别为（r=0.711,P〈0.05）、（r=0.845,P〈0.01）、（r=0.862,P〈0.01）和（r=0.724,P〈0.051）。结论：可溶性CD83通过活化DC细胞并激活补体系统,参与系统性红斑狼疮的发生发展,联合可溶性CD83和多种自身抗体的检测,能更明确系统性红斑狼疮患者病情的严重程度,有利于SLE的诊断和治疗。     

系统性红斑狼疮患者血清中CD83 与自身抗体的表达及其相互关系

目的:检测系统性红斑狼疮(systemic lupus erythematosus,SLE)患者血清中 CD83(soluble CD 83,sCD 83)和多种自身抗体的表达水平,并探讨其相互关系.方法:ELISA 检测患者可溶性 CD 83 和AnuA的表达,应用间接免疫荧光的方法检测抗cmDNA 抗体,应用乳凝法检测血清中的DNP,采用胶体金标记和快速膜渗滤技术测定血清中的抗 dsDNA 抗体.结果:对照组患者血清中可溶性 CD83 的表达为(0.26±0.10)ng/ml,实验组患者血清中可溶性 CD83 的表达为(5.56±0.72)ng/mI.与对照组相比,实验组患者血清中可溶性CD 83的平均浓度明显升高.在抗dsDNA抗体阴性的 51 例系统性红斑狼疮患者中 AnuA 的阳性率明显高于抗DNP 抗体和抗 cmDNA 抗体,同样在抗 DNP 抗体阴性的 58 例系统性红斑狼疮患者中 AnuA 的阳性率明显高于 dsDNA 抗体和抗 cmDNA 抗体.系统性红斑狼疮患者中可溶性 CD83 的水平(<2.68 ng/ml)与各种自身抗体(抗 dsDNA 抗体、AnuA、抗DNP抗体和抗 cmDNA 抗体) 水平的相关系数分别为(r＝0.542,0.613,0.489和0.367).具有高水平可溶性CD83的系统性红斑狼疮患者( ≥2.68 ng/ml),与各种自身抗体(抗dsDNA抗体,AnuA,抗 DNP 抗体和抗cmDNA 抗体)水平的相关系数分别为(r＝0.711,P<0.05)、(r＝0.845,P<0.01)、(r=0.862,P<0.01)和(r=0.724,P<0.051).结论:可溶性CD83通过活化DC细胞并激活补体系统,参与系统性红斑狼疮的发生发展,联合可溶性 CD83 和多种自身抗体的检测,能更明确系统性红斑狼疮患者病情的严重程度,有利于 SLE 的诊断和治疗.     

Degradation of neutrophil extracellular traps co-varies with disease activity in patients with systemic lupus erythematosus

Introduction

The ability to degrade neutrophil extracellular traps (NETs) is reduced in a subset of patients with systemic lupus erythematosus (SLE). NETs consist of chromatin covered with antimicrobial enzymes and are normally degraded by DNase-I, an enzyme which is known to have reduced activity in SLE. Decreased ability to degrade NETs is associated with disease activity. In the current study we investigated how the ability of serum from SLE patients to degrade NETs varies during the course of SLE as well as what impact this may have for the clinical phenotype of SLE.

Methods

Serum from 69 patients with SLE, included in a prospective study, was taken every 60 days for a median of 784 days. The ability of serum to degrade NETs was determined and associated with clinical parameters occurring before and at the time of sampling, as well as after sampling by using conditional logistic regression.

Results

As many as 41% of all patients in the study showed decreased ability to degrade NETs at least once, but with a median of 20% of all time points. Decreased degradation was associated with manifestations of glomerulonephritis as well as low complement levels and elevated levels of antibodies directed against histones and DNA. Furthermore, the odds ratio for the patient to develop alopecia and fever after an episode of decreased NETs degradation was increased by four to five times compared to normal.

Conclusions

Decreased degradation of NETs is associated with clinical manifestations in SLE and may contribute to disease pathogenesis. Potential therapeutics restoring the ability to degrade NETs could be beneficial for certain patients with SLE.     

Effect of trichostatin A on human T cells resembles signaling abnormalities in T cells of patients with systemic lupus erythematosus: a new mechanism for TCR zeta chain deficiency and abnormal signaling

Trichostatin A (TSA) is a potent reversible inhibitor of histone deacetylase, and it has been reported to have variable effects on the expression of a number of genes. In this report, we show that TSA suppresses the expression of the T cell receptor zeta chain gene, whereas, it upregulates the expression if its homologous gene Fc(epsilon) receptor I gamma chain. These effects are associated with decreased intracytoplasmic-free calcium responses and altered tyrosine phosphorylation pattern of cytosolic proteins. Along with these effects, we report that TSA suppresses the expression of the interleukin-2 gene. The effects of TSA on human T cells are predominantly immunosuppressive and reminiscent of the signaling aberrations that have been described in patients with systemic lupus erythematosus.     

三氧化二砷对系统性红斑狼疮患者外周血淋巴细胞凋亡和IL-10分泌的影响

目的观察不同浓度三氧化二砷（As2O3）对活动期系统性红斑狼疮（SLE）患者外周血淋巴细胞凋亡及白介素10（IL-10）分泌的影响。方法收集15例未曾用过激素及免疫抑制剂治疗并排除其它类型的自身免疫性疾病及感染性疾病的初诊SLE患者和同期15例健康体检者（健康对照组）的外周血,分别于不同浓度As2O3干预培养后12h和24h采用VnnexinV＼PI染色定量分析外周血淋巴细胞凋亡率,采用酶联免疫吸附法（ELISA）检测培养上清液中IL-10的含量。结果SLE组患者和健康对照组在不同As2O3浓度下12h和24h的凋亡率均增加（P〈0．05）;不同浓度As2O3诱导SLE患者在12h和24h淋巴细胞凋亡率明显高于健康对照组（P〈0．05）;且随As2O3干预浓度的增加,两组外周血淋巴细胞凋亡率均增加（P〈0．05）。SLE组患者外周血淋巴细胞在体外培养后分泌IL-10水平明显高于健康对照组（P〈0．05）,且As2O3能显著抑制其分泌,As2O3对健康对照组无影响（P〉0．05）。结论As2O3能诱导外周血淋巴细胞凋亡,并且具有时间和浓度依赖性,提示As2O3通过引起淋巴细胞凋亡发挥治疗作用;As2O3抑制SLE患者外周血淋巴细胞分泌IL-10可能是其发挥治疗作用的重要机制之一。     

DNA methylation similarities in genes of black South Africans with systemic lupus erythematosus and systemic sclerosis

Background

Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are systemic autoimmune connective tissue diseases that share overlapping clinico-pathological features. It is highly probable that there is an overlap in epigenetic landscapes of both diseases. This study aimed to identify similarities in DNA methylation changes in genes involved in SLE and SSc. Global DNA methylation and twelve genes selected on the basis of their involvement in inflammation, autoimmunity and/or fibrosis were analyzed using PCR arrays in three groups, each of 30 Black South Africans with SLE and SSc, plus 40 healthy control subjects.

Results

Global methylation in both diseases was significantly lower (<25 %) than in healthy subjects (>30 %, p = 0.0000001). In comparison to healthy controls, a similar gene-specific methylation pattern was observed in both SLE and SSc. Three genes, namely; PRF1, ITGAL and FOXP3 were consistently hypermethylated while CDKN2A and CD70 were hypomethylated in both diseases. The other genes (SOCS1, CTGF, THY1, CXCR4, MT1-G, FLI1, and DNMT1) were generally hypomethylated in SLE whereas they were neither hyper- nor hypo-methylated in SSc.

Conclusions

SSc and SLE patients have a higher global hypomethylation than healthy subjects with specific genes being hypomethylated and others hypermethylated. The majority of genes studied were hypomethylated in SLE compared to SSc. In addition to the commonly known hypomethylated genes in SLE and SSc, there are other hypomethylated genes (such as MT-1G and THY-1) that have not previously been investigated in SLE and SSc though are known to be hypermethylated in cancer.     

Salivary levels of inflammatory cytokines and their association to periodontal disease in systemic lupus erythematosus patients. A case-control study

Both Systemic Lupus Erythematosus (SLE) and periodontal disease (PD) present a similar immunological profile mainly characterized by altered cytokine levels. In this study we sought to investigate the salivary levels of inflammatory cytokines and their association with PD in SLE patients. 60 patients with SLE and 54 systemically healthy individuals underwent a full periodontal clinical examination. They were then grouped according to their periodontal status. Stimulated saliva was collected in order to evaluate the salivary levels of interferon (IFN-γ), Interleukin (IL)-10, IL-17, IL-1β, and IL-4. Systemically healthy individuals with periodontitis (group P) presented higher levels of cytokines when compared to systemically healthy individuals, with no periodontal disease (group S) (p < 0.05). Additionally, in the P group, patients presented similar levels of cytokines to those of the patients with SLE, regardless of the presence of PD (p > 0.05), for most of the analyzed cytokines. There was a positive correlation in SLE patients, including IL-1β and all periodontal clinical parameters (p < 0.05), and between IL-4 and gingival bleeding index and the presence of biofilm (p < 0.05). Thus, our results confirmed, that patients with PD showed higher salivary levels of cytokines and, in SLE patients, the increased levels of salivary cytokines were observed even in the absence of periodontitis. IL-1β and IL-4 salivary levels were also positively correlated with periodontal status indicating their potential as markers of the amount and extent of periodontal damage in patients with SLE.     

Expression of CD55 and CD59 on peripheral blood cells from systemic lupus erythematosus (SLE) patients

CD55 and CD59 are glycosylphosphatidylinositol-anchored proteins with complement inhibitory properties. CD55 inhibits the formation of C3 convertases, and CD59 prevents the terminal polymerisation of the membrane attack complex. It has been reported that SLE patients seems to have an acquired deficiency of these proteins associated with secondary autoimmune haemolytic anaemia and lymphopenia. The aim of this study was to evaluate the presence of altered CD55 and CD59 expression on peripheral blood cells from SLE patients. Flow cytometric analyses were performed on red and white blood cells from 23 SLE patients and 23 healthy controls. We observed more CD55- and CD59-lymphocytes (p = 0.005 and p = 0.019, respectively), and CD59-granulocytes (p = 0.045) in SLE patients than in controls. These results suggest there is an altered pattern of CD55 and CD59 expression on the peripheral blood cells of SLE patients, and it may play a role in the cytopenias in these patients.     

SLE带状疱疹患者外周血CD4~+CD28~+和CD4~+CD25~+FoxP3~+调节性T细胞的表达及相关性研究

目的:检测系统性红斑狼疮(systemic lupus erythematosus,SLE)合并带状疱疹患者外周血CD4~+CD28~+和CD4~+CD25~+Fox P3~+调节性T细胞的表达及相关性,探讨其在SLE合并带状疱疹发病中的临床意义。方法:采用流式细胞术检测30例SLE患者、30例SLE合并带状疱疹患者及30例健康对照者外周血中CD4~+/CD8~+T淋巴细胞亚群表面CD28的表达及CD4~+CD25~+Fox P3~+Treg细胞的表达水平,并分析SLE合并带状疱疹患者外周血CD4~+CD28~+和CD4~+CD25~+Fox P3~+调节性T细胞表达的相关性。结果:SLE合并带状疱疹组患者急性期外周血CD4~+T淋巴细胞比率、绝对计数显著降低,CD4~+、CD8~+T淋巴细胞表面的CD28表达下调,CD4~+CD25~+Fox P3~+Treg细胞水平显著高于SLE组及健康对照组,SLE合并带状疱疹组患者外周血CD4~+CD25~+Fox P3~+Treg水平与CD4~+CD28~+水平成负相关(P均0.05)。结论:SLE合并带状疱疹患者CD4~+、CD8~+T细胞活化异常,CD4~+CD25~+Fox P3~+Treg细胞可能参与抑制了T细胞的活化。