Inactive SLE Patients Research Articles

Evaluation of survivin expression and regulating miRNAs of survivin expression in peripheral blood mononuclear cells in systemic lupus erythematous patients.

Systemic lupus erythematosus is a multisystemic rheumatic disease with different clinical features. Disturbance in apoptosis regulation seems to be a major factor in SLE development. Survivin plays a key role in mitosis and inhibiting apoptosis. A study was conducted to examine the expression level of survivin and miRNAs that affect survivin transcript levels in patients with SLE. We isolated peripheral blood mononuclear cells from 50 inactive SLE patients and 50 healthy controls. RNA is extracted and converted to cDNA. The quantitative real-time polymerase chain reaction is conducted to assess the expression levels of survivin total and its variants with effective miRNAs in PBMCs. Expression levels of miR-34a-5p (fold change = 1.5, p++ = 0.027), and 218-5p (fold change = 1.5, p++ = 0.020) were significantly increased. While miR-150-5p (fold change = 0.56, p++ = 0.003) was significantly decreased. The mRNA expression of survivin-WT (fold change = 0.63, p++ = 0.002) was significantly downregulated in SLE patients compared to the healthy controls. Survivin total and its two major variants (survivin-2B, and survivin-ΔEx3) did not differ significantly between SLE patients and controls. Although survivin-TS and its two variants (survivin-2B, and survivin-ΔEx3) were not differently expressed in SLE patients, survivin-WT had altered expression. Despite aberrant miRNA expression in PBMCs from SLE patients, survivin and miRNA expression were not associated with leukopenia. The pathogenesis of SLE disorder might be linked to survivin's other roles in the immune system aside from anti-apoptotic functions.

Correlation of simple hematological parameters with disease activity and damage indices among Egyptian patients with systemic lupus erythematosus

ObjectiveTo evaluate the correlation of different hematological parameters in lupus patients with SLE disease activity index (SLEDAI), the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI), and some laboratory data related to kidney functions in active patients with nephritis. Material and methods80 inactive SLE patients (SLEDAI score<10 points), and 80 active patients (SLEDAI≥10 points) were enrolled in this study. All patients underwent full medical history taking, clinical evaluation including calculation of SLEDAI and SLICC/ACR DI scores, and laboratory investigations including complete blood count. The two groups were compared regarding different disease parameters. Correlations of some hematological parameters with SLEDAI, SLICC/ACR DI scores and some laboratory data related to kidney function in patients with nephritis were made. ResultsThe active group showed statistically significantly higher mean NLR (P=0.000), NC3R (P=0.000), MLR (P=0.000), PLR (P=0.000), and RDW (P=0.001), and statistically significantly lower mean MPV (P=0.002). The mean MLR (P=0.018) and PLR (P=0.005) were statistically significantly higher in the active patients with nephritis. For both groups, there were no significant correlations between studied parameters and SLEDAI or SLICC/ACR DI, except with NC3R values in the active group which were associated with SLEDAI (r=.221, P=0.049). ConclusionThe hematological parameters in SLE have promising potential clinical application as a novel activity marker, especially in patients with nephritis.

Aberrant expansion of follicular helper T cell subsets in patients with systemic lupus erythematosus.

ObjectiveSystemic lupus erythematosus (SLE) is a chronic and complex autoimmune disease characterized by multiple autoantibodies, resulting in multiple organ and tissue damages. These pathogenic autoantibodies produced by B cells are closely correlated with follicular helper T (Tfh) cell subsets that play a fundamental role in the pathogenesis of SLE. The aim of the present study was to study the phenotype and role of circulating Tfh (cTfh) cell subsets and associated B cell subpopulations in active and inactive SLE patients.MethodsThirty SLE outpatients and 24 healthy controls (HCs) were enrolled in this study. The frequency of cTfh cell and B cell subsets in peripheral blood mononuclear cells (PBMCs) and the plasma levels of eight cytokines were determined by flow cytometry, and plasma IL-21 levels were measured by ELISA. Meanwhile, we used MRL/lpr mice as the model of SLE to research the alterations of Tfh cells in the thymus and spleen of mice.ResultsFrequencies of CD4+CXCR5+CD45RA-effector cTfh cells, PD1+cTfh, PD1+ICOS+cTfh, PD1+cTfh1, PD1+cTfh2, PD1+cTfh17, and PD1+ICOS+cTfh1 cells as well as plasmablasts showed significant differences among HC, active and inactive SLE patients. Moreover, cytokines typically associated with cTfh cells, including IL-6 and IL-21, were elevated in active SLE patients compared to inactive SLE patients and HCs. Additionally, a positive correlation was observed between PD1+ICOS+ cTfh or PD1+ICOS+ cTfh1 cell frequencies and plasmablasts or IL-21 levels, as well as between plasmablasts. We also found PD1+ICOS+ Tfh cells expansion in both thymus and spleen of MRL/lpr mice, accompanied by increased frequencies in B cells and plasmablasts, meanwhile, cTfh1which expressing IFN-γ was increased in the peripheral blood of MRL/lpr mice.ConclusionTfh cell subsets and plasmablasts may play a fundamental role in the pathogenesis of SLE and may provide potential targets for therapeutic interventions for SLE.

The phenotype of CD3-CD56bright and CD3-CD56dim natural killer cells in systemic lupus erythematosus patients and its relation to disease activity.

IntroductionSystemic lupus erythematosus (SLE) patients have decreased natural killer (NK) cell counts. The decrease in the number of NK cells has implications for a decrease in the function of NK cells which can affect the progression of SLE disease. The study aim was to determine profiles of CD3–CD56bright and CD3–CD56dim NK cells in SLE patients and their relation to disease activity.Material and methodsThis study included 36 patients of SLE who fulfilled the ACR 1997/SLICC 2012 criteria, women aged 18–49 years. Disease activity was assessed by the Mex-SLEDAI. Peripheral blood samples from SLE patients were analyzed by flow cytometry to evaluate NK cell subsets, according to differential expression of the main subset of NK cells, which is CD3–CD56bright and CD3–CD56dim.ResultsThe mean percentage of regulatory NK cell count (CD3–CD56bright) in active SLE patients was significantly lower (p = 0.000) than in inactive SLE patients. The mean percentage of cytotoxic NK cell count (CD3–CD56dim) in active SLE patients was significantly (p = 0.000) higher than in inactive SLE patients. A correlation was observed between two subsets of NK cells with disease activity (p = 0.00). The percentage of CD3–CD56bright NK cells was negatively correlated with disease activity (r = –0.766), whereas the percentage of CD3–CD56dim NK cells positively correlated with disease activity (r = 0.761).ConclusionsThere is a difference in the mean percentage of the number of NK cells (CD3–CD56+) in both a subset of regulatory NK cells (CD3–CD56bright) and cytotoxic NK cells (CD3–CD56dim) in active and inactive SLE patients and it is closely related to SLE disease activity.

Urinary CD163 is a marker of active kidney disease in childhood-onset lupus nephritis.

The objective of this study was to evaluate the utility of urine CD163 for detecting disease activity in childhood-onset SLE (cSLE) patients. Sixty consecutive pediatric patients fulfilling four or more ACR criteria for SLE and 20 healthy controls were recruited for testing of urinary CD163 using ELISA. SLE disease activity was assessed using the SLEDAI-2K. Urine CD163 was significantly higher in patients with active LN than inactive SLE patients and healthy controls, with receiver operating characteristics area under the curve values ranging from 0.93 to 0.96. LN was ascertained by kidney biopsy. Levels of CD163 significantly correlated with the SLEDAI, renal SLEDAI, urinary protein excretion and C3 complement levels. Urine CD163 was also associated with high renal pathology activity index and chronicity index, correlating strongly with interstitial inflammation and interstitial fibrosis based on the examination of concurrent kidney biopsies. Urine CD163 emerges as a promising marker for identifying cSLE patients with active kidney disease. Longitudinal studies are warranted to validate the clinical utility of urine CD163 in tracking kidney disease activity in children with lupus.

Clinical significance of red blood cell distribution width in systemic lupus erythematosus patients

BackgroundSystemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with wide variety of clinical presentations. Recently, red blood cell distribution width (RDW) has been used as an inflammatory marker, similar to the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) where systemic inflammation has been linked to increased RDW. Many researches have assessed independently selective different hematological markers that may reflect disease activity.Our study aims to examine a number of hematological parameters that could reflect disease activity and to assess if there is a relationship between different hematological parameter (RDW, neutrophils and lymphocytes) to reflect SLE activity using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).ResultsThe study comprised 60 SLE patients (52 females and 8 males) with a mean age of 34.53 years and mean disease duration was 4.085 years. The RDW values were significantly higher (p < 0.001) when comparing active patients (16.64 ± 4.7) versus inactive patients (13.16 ± 2.67) and controls (12.7 ± 1.13). Otherwise, insignificant differences were reported when comparing inactive SLE patients versus the control group (p = 0.242). There were no significant correlations (p > 0.05) between neutrophil count and lymphocyte count with C3, C4, SLEDAI score, 24 h urinary proteins, platelets count but significant only with hemoglobin level (p = 0.001).ConclusionIncreased RDW is connected with active disease status of SLE patients. RDW could be used as a surrogate marker of the inflammation rather than neutrophil and lymphocyte count. It is a simple and easy testing included in CBC thus RDW could be used as a possible indicator to assess disease activity.

Low-density lipoprotein from active SLE patients is more atherogenic to endothelial cells than low-density lipoprotein from the same patients during remission.

SLE patients have an enhanced risk of atherosclerosis and cardiovascular disease. However, the increased prevalence of cardiovascular disease is not fully explained by traditional Framingham cardiovascular risk factors. Specific features of low-density lipoprotein (LDL) particles, other than plasma concentration, may induce accelerated atherosclerosis at early stages in these patients. Thus, we aimed to explore the impact of LDL from both active and inactive SLE patients on human aortic endothelial cells. Human aortic endothelial cells were stimulated with the same concentration of LDL particles isolated from pooled serum that was collected from 13 SLE patients during both active and inactive states. Gene expression and cell migration assays were performed. Circulating LDL particles obtained from healthy volunteers and SLE patients in both remission and flare states were comparable in terms of number, cholesterol and triglyceride content, and net electric charge. Stimulation of cells with LDL from active SLE patients induced the expression of vascular cell adhesion molecule 1 (∼2.0-fold, P < 0.05), monocyte chemoattractant protein 1 (∼2.0-fold, P < 0.05) and matrix metallopeptidase 2 (∼1.6-fold, P < 0.01) compared with cells stimulated with LDL from inactive SLE patients. Additionally, LDL extracted from active patients increased cell migration in a wound-healing assay (1.4-fold, P < 0.05). Our data show that, at the same LDL concentration, LDL from active SLE patients had increased proatherogenic effects on endothelial cells compared with LDL from the same patients when in an inactive or remission state.

Urinary activated leukocyte cell adhesion molecule as a novel biomarker of lupus nephritis histology

BackgroundLupus nephritis (LN) is one of the most severe complications of SLE patients. We aim to validate urinary ALCAM as a biomarker in predicting renal disease histpathology in a Chinese lupus cohort.MethodsIn this cross-sectional study, a total of 256 patients and controls were recruited. Urinary levels of ALCAM were determined by ELISA. Renal histopathology was reviewed by an experienced renal pathologist.ResultsUrinary ALCAM levels were significantly increased in active LN patients when compared to active SLE patients without renal involvement (p < 0.001), inactive LN patients (p = 0.023), inactive SLE patients without renal involvement (p < 0.001), and healthy controls (p < 0.001). Correlation analysis revealed a positive correlation between urinary ALCAM and general disease activity—SLEDAI score (r = 0.487, p < 0.001), as well as renal disease activity—rSLEDAI (r = 0.552, p < 0.001) and SLICC RAS (r = 0.584, p < 0.001). Urinary ALCAM also correlated with lab parameters including 24-h urine protein, hemoglobin, and complement 3. Moreover, urinary ALCAM levels were significantly increased in class III and IV (proliferative) LN as compared to those in class V (membranous) LN. It outperformed conventional biomarkers (anti-dsDNA antibody, C3, C4, proteinuria) in discriminating the two groups of LN. On renal histopathology, urinary ALCAM levels correlated positively with activity index (r = 0.405, p < 0.001) but not chronicity index (r = 0.079, p = 0.448).ConclusionUrinary ALCAM is a potential biomarker for predicting renal pathology activity in LN and may serve as a valuable surrogate marker of renal histopathology.

Evaluate the Correlation Between Antioxidant Capacity and Interferon Γ Level with the Disease Activity of Sle Patients in Iraqi Woman

This study was aimed to assess total antioxidants capacity as well as interferon γ cytokine in female with Lupus Erythematosus and their relationship with disease activity. Fifty‑two female SLE patients diagnosed and classified according to the American College of Rheumatology (ACR)criteria admitted to Department of Rheumatology at Baghdad and alyarmook teaching hospital. SLE patients were clinically evaluated and disease activity assessed using the SLE indicator and a particular focus on the onset, duration of the disease, and the body organs affected by the disease. Routine laboratory tests were performed for all patients. The levels of serum cytokines and antioxidant capacity were measured by enzyme linked immunosorbent assays (ELISA).In the case of total antioxidant capacity, the result showed that mean values were significantly lower in active lupus patients than inactive lupus and controls (2.050±0.276, 1.322±0.254, 1.286±0.133) respectively, and, the mean of values of interferon γ cytokine in active and inactive SLE patients were significantly higher than control group (83.275±15.612,71.335±14.948,32.049±7.519) respectively.

Identification of perturbations in macrophage polarization in active systemic lupus erythematosus.

Abstract SLE is characterized by abnormalities in B cell and T cell function, but the role of disturbances in the polarization of macrophages (Mφ) into functional subpopulations is unclear. Gene expression profiles were analyzed to identify differentially expressed (DE) genes between healthy controls and patients with either inactive or active SLE. While hundreds of DE genes were identified in B and T cells of active SLE patients, there were no DE genes found in B or T cells from patients with inactive SLE compared to healthy controls. In contrast, large numbers of DE genes were found in myeloid cells (MC) from both active and inactive SLE patients, and many of these were Mφ polarization genes (M1: STAT1, SOCS3; M2: STAT3, STAT6, CD163). Weighted gene correlation network analysis (WGCNA) was used to identify modules of genes associated with clinical activity in SLE patients; among these were disease activity-correlated modules containing polarization signatures of predominantly M1-associated genes. No disease activity-correlated modules were enriched in M2-associated genes. Pathway and upstream regulator analysis of DE genes from both active and inactive SLE MC were cross-referenced with high-scoring hits from the drug discovery Library of Integrated Network-based Cellular Signatures (LINCS) to identify new strategies to treat both stages of SLE. In summary, altered MC gene expression is characteristic of both active and inactive SLE, and disease activity is associated with an alteration in the MC signature towards the M1 phenotype. These data suggest that while B and T cell hyperactivity are associated with active SLE pathology, myeloid cells potentially direct flare-ups and remission by switching between M1- and M2-like polarization states.

Low Expression and Clinical Value of hsa_circ_0049224 and has_circ_0049220 in Systemic Lupus Erythematous Patients.

BackgroundThe aim of this study was to discuss the possible roles and clinical value of 2 circRNAs (hsa_circ_0049224 and has_circ_0049220) in SLE patients.Material/MethodsReverse-transcription real-time polymerase chain reaction (RT-PCR) was conducted to detect the expressions of hsa_circ_0049224, has_circ_0049220, and DNMT1 in peripheral blood mononuclear cells (PBMCs) from 18 diagnosed SLE patients and 10 healthy controls.ResultsWe found that the expressions of hsa_circ_0049224 and has_circ_0049220 in healthy control groups were both much higher than those in inactive and active SLE patients. The expression level of DNMT1 is positively correlated with the expressions of hsa_circ_0049224 and has_circ_0049220. Moreover, there was a negative correlation between the SLE Disease Activity Index (SLEDAI) and the expressions of hsa_circ_0049224 and has_circ_0049220. We also found that these 2 circRNAs are associated with some clinical characteristics of SLE.ConclusionsHsa_circ_0049224 and has_circ_0049220 are probable factors involved in the pathogenesis of SLE, and they have potential clinical value in SLE.

Identification of perturbations in macrophage polarization in active systemic lupus erythematosus.

Abstract SLE is characterized by abnormalities in B cell and T cell function, but the role of disturbances in the polarization of macrophages (Mφ) into functional subpopulations has not been delineated. Gene expression profiles were analyzed to identify differentially expressed (DE) genes between healthy controls and patients with either inactive (SLEDAI &amp;lt; 6) or active (SLEDAI ≥ 6) SLE. While hundreds of DE genes were identified in B and T cells of active SLE patients (760 and 164 genes respectively), there were no DE genes found in B or T cells from patients with inactive SLE compared to healthy controls. In contrast, large numbers of DE genes were found in myeloid cells from both active (2,135) and inactive (1,260) SLE patients. Many of these DE genes were known to play roles in Mφ polarization, including the M1 genes STAT1 and SOCS3 and the M2 genes STAT3, STAT6, and CD163. M1-associated genes were far more frequent in data sets from active versus inactive SLE patients. To further characterize the relationship between M1 phenotype and disease activity, Weighted Gene Cluster Network Analysis (WGCNA) was used to identify modules of genes associated with clinical activity in SLE patients. Among these were disease activity-correlated modules containing polarization signatures of predominantly M1-associated genes. No disease activity-correlated modules were enriched in M2-associated genes. In summary, altered Mφ gene expression is characteristic of both active and inactive SLE. However, disease activity is associated with an alteration in the functional differentiation of Mφ to the M1 proinflammatory phenotype. This switch in Mφ phenotype is related to the altered expression of genes by T cells and B cells characteristic of active SLE.

ASSOCIATION BETWEEN DISEASE ACTIVITY AND IL-17A/F, IL-23 AND IL-12/23 (p40) PRODUCTION BY PERIPHERAL BLOOD T LYMPHOCYTES IN BEHCET’S DISEASE

Abstract Exact pathogenesis of Behcet’s Disease (BD) hasn’t been known but recent studies suggest it’s a genetic-based and immune-related disease. We aimed to investigate the association between disease activity and Th1, Th17 and Treg cells in BD patients via IL-17A/F, IL-23, IL-12/23p40, IL-35 produced by these cells. We also compared our findings with those of SLE patients to investigate their specificity for immunopathogenesis of BD. 15 active and 15 inactive BD patients, 12 active and 12 inactive SLE patients and 12 sex &amp; age-matched healthy controls were involved. Peripheral blood lymphocyte cultures were done. Supernatants from PHA-stimulated and -unstimulated cultures were measured for IL-17A/F, IL-12/23p40, IL-23 and IL-35 levels in time-dependent manner (48 and 72 hrs) by ELISA. For disease activity International Study Group Diagnostic Criteria and SLEDAI index were used for BD and SLE, respectively. IL-17 and IL-23 increased parallelly in both BD and SLE; IL-17 was higher but another Treg cytokine IL-35 was lower in active BD and active SLE compared to healthy controls. After 48 and 72 hrs of PHA stimulation the highest levels of IL-17A/F, IL-22723p40 and IL-23 were measured in active BD followed by active SLE. Our data suggest that IL-17, IL-23 and IL-12/23p40; Th17 and Th1 responses play role in pathogenesis of BD. Finding IL-35 to be lower in active BD compared to inactive BD patients and healthy controls made us think that there can be a plasticity between Th17 and Treg cells depending on disease activity. This is the first time such plasticity is suggested for BD in literature. Our findings also show that IL-17/23 axis contributes to pathogenesis of SLE (another inflammatory rheumatic disease) in addition to other mechanisms like in BD.

Negative Correlation Between miR-326 and Ets-1 in Regulatory T Cells from new-Onset SLE Patients

To analyze the relationship between miR-326 and Ets-1 mRNA levels in Treg cells and clinical manifestations in patients with SLE and explore the role of miR-326 and Ets-1 in the pathogenesis and activity of SLE. Twenty-five new-onset SLE patients without treatment, twenty-eight inactive SLE patients (SLEDA ≤ 4) and twenty-two healthy controls were included in the present study. Clinical data of SLE patients were recorded. Treg cells were purified by MACS from 20ml peripheral blood, in which the quantity of miR-326 and Ets-1 mRNA were assessed by real-time PCR. Data were analyzed using SPSS Version 17.0. The nonparametric Mann-Whitney U test was used to compare the groups, The Spearman test was used for correlation analyses. Two-tailed p values <0.05 were considered statistically significant. 1.The level of miR-326 was significantly higher in Treg cells from SLE patients [1.98(0.592,6.148)] than that in healthy controls [0.921(0.345, 1.879)] (p = 0.032). The difference between new-onset SLE patients [6.192(0.673, 15.298)] and healthy controls was significant (p = 0.019). Significant difference of the miR-326 expression was found between new-onset SLE patients with serous cavity effusion and new-onset SLE patients without it(P<0.05). Significant positive correlation was found between the expression of miR-326 mRNA in Treg cells with CRP and anti-C1q antibody from new-onset SLE patients. 2. The level of Ets-1 mRNA was decreased in SLE patients [0.382(0.232, 0.572)] compared to healthy controls(p = 0.013). The difference was also found in new-onset SLE patients [0.222(0.125, 0.296)] while compared to healthy controls. Also, the level in new-onset SLE patients was lower than that in inactive SLE patients [0.482(0.398, 0.512)] (p = 0.001). 3. Negative correlation was found between miR-326 and Ets-1 mRNA expression in Treg cells from new-onset SLE patients (r = -0.583 p = 0.01). 4. There was no correlation of miR-326 or Ets-1 mRNA expression with SLEDAI. The increase of miR-326 expression in Treg cells from SLE patients may inhibit the expression of Ets-1 to participate in the pathological process of SLE.

Increased serum levels of S100A8/A9 and S100A12 are associated with cardiovascular disease in patients with inactive systemic lupus erythematosus

Patients with SLE have an increased morbidity and mortality from cardiovascular disease (CVD). The reason for this is not entirely understood, but is believed to be partly related to the long-lasting inflammatory process seen in SLE. The aim of the present study was to investigate whether there is an association between CVD and serum levels of the proinflammatory proteins S100A8/A9 and S100A12 in SLE. Serum levels of S100A8/A9 and S100A12 were measured with ELISA in 237 SLE patients with clinically inactive disease and without infections, as well as in 100 healthy individuals. Cardiovascular manifestations were defined according to the SLICC/ACR Damage Index (SLICC/ACR-DI). Serum levels of S100A8/A9 were elevated in our inactive SLE patients as compared with healthy individuals (P < 0.0001), which was not seen for S100A12 (P = 0.12). SLE patients with a history of CVD had increased serum levels of both S100A8/A9 and S100A12 compared with patients with no CVD or venous thromboembolism (P = 0.003 and P = 0.006, respectively). The presence of organ damage according to SLICC/ACR-DI was associated with an increase in both S100A8/A9 and S100A12 serum levels (P = 0.001 and P = 0.006, respectively). Elevated serum levels of S100A8/A9 and S100A12 may be used as an indicator of severe disease and CVD in SLE, suggesting that SLE patients with elevated serum S100A8/A9 and S100A12 concentrations may benefit from more intense cardiovascular primary preventive strategies and possibly also from more intense and early immunosuppressive treatment.

AB0029 Characterising monocyte responses to toll-like receptors in irish sle patients.

BackgroundSystemic Lupus Erythematosus(SLE) involves complex interactions between the innate and adaptive immune systems. Monocytes are increasingly recognised to play a key role in the dysregulated immune response seen in SLE,...

AB0198 Defining CD4+ T cell- and monocyte-specific interferon signatures in active, inactive and autologous stem cell transplanted lupus patients by global gene expression profiling

BackgroundSystemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that affects multiple organs, whose pathology is mainly caused by the augmented interferon (IFN) signaling pathway.ObjectivesThe objective of this study...

The Tie2 Receptor Antagonist Angiopoietin-2 in Systemic Lupus Erythematosus: Its Correlation with Various Disease Activity Parameters

Background: Systemic lupus erythematosus is one of the autoimmune diseases characterized by multisystem involvement associated with autoantibody and immune complex vasculitis along with endothelial cell damage. Objective: to study the possible role of Angiopoietin- 2 (Ang-2) as a recently highlighted inflammatory and angiogenic mediator in the pathogenesis of SLE and its correlation with the state of another inflammatory marker, P-Selectin, as well as with various markers of the disease activity. Patients and methods: The present study included 3 main groups: active SLE patients (group I), inactive SLE patients (group II) and healthy normal control subjects (group III). Groups I and II were subjected to disease activity assessment using the SLEDAI scoring system and measurement of plasma Ang-2 and P-Selectin by ELISA in addition to various laboratory investigations to assess disease activity as: Complete blood count, ESR, serum creatinine, C3, C4 and 24-h urinary proteins. Results: The mean level of Plasma Ang-2 and P-selectin showed a high significant increase in active group compared to inactive SLE patients and control subjects (p < 0.001).There was a significant positive correlation between Ang-2, P-Selectin, and each of SLEDAI score and 24-h urinary proteins in all SLE patients as well as in the active group, and Ang-2 was a significant independent marker for proteinuria. A significant negative correlation was found between Ang-2, P-Selectin and each of C3, C4. Ang-2 and P-Selectin showed a high sensitivity and specificity in the patients with SLE. Conclusion: Our study suggests that Ang-2 may be a more useful marker than P-Selectin, C3 and C4 in the assessment of disease activity.

Defining T helper (CD4) cell-specific disease signatures in active, inactive and autologous stem cell transplanted lupus patients by global gene expression profiling

BackgroundSystemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that affects multiple organs, whose pathology is mainly caused by the augmented interferon (IFN) signaling pathway. The objective of this...

Expression of TGFβ1 and Its Signaling Components by Peripheral Lymphocytes in Systemic Lupus Erythematosus

Transforming growth factor beta1 (TGFbeta1) is an important immunosuppressive cytokine. Defects in its production by lymphocytes and the failure of TGFbeta1 to regulate immunological functions have been described in SLE. Expression of TGFbeta1 and the related signaling pathway was studied in the peripheral lymphocytes of SLE patients. The total plasma TGFbeta1 level in active and inactive SLE patients compared to healthy controls was also measured. TGFbeta1 and all downstream signaling elements were expressed in normal cells. However, in more than 50% of SLE patients the isolated T cell population showed no TGFbeta1 mRNA expression and at least one member of the TGFbeta1 pathway was also missing (TGFbeta-RI, Smad2 and Smad3) in more than half of the patients. Total plasma TGFbeta1 level was increased in both active and inactive SLE groups compared to normal controls (p< 0.05). These data raise questions about the availability of TGFbeta1 signaling in lymphocytes in SLE patients, however, the elevated total plasma TGFbeta1 level suggests that the failure of TGFbeta1 effects is not the consequence of low level of this cytokine in SLE.