Decreased sleep quality in patients with systemic lupus erythematosus: a meta-analysis

Clinical Rheumatology - To obtain a reliable estimation on the sleep quality in patients with systemic lupus erythematosus (SLE) and identify the main sleep problems, a meta-analysis was performed....     

T-cell adhesion to endothelial cells in systemic lupus erythematosus

Summary To investigate the pathogenesis of the lymphopenia in systemic lupus erythematosus (SLE), we examined the adhesion of these T cells to endothelial cells (EC). T cells from 10 lymphopenic patients with active SLE showed significantly reduced adhesion to unstimulated and interleukin-1 (IL-1)-stimulated human EC monolayers when compared with T cells from age, sex, and race matched normal control individuals. Percentage decreases from control values () in the measured percentage of T cells adherent to unstimulated and IL-1-stimulated EC were 36.4% (P<0.025) and 34.0% (P<0.005), respectively. Percentage adhesion of phorbol ester-treated T cells of SLE patients was also reduced compared with similarly treated T cells of control patients; the decrease was 22.8% (P<0.025). No abnormality was detected in the adhesion to EC of T cells from patients with asthma who were receiving corticosteroids, suggesting that the abnormality in the SLE T cells was related to the disease process itself. The reduced adhesion of the circulating T cells may be a consequence of the withdrawal from the blood of more strongly adherent cells in the course of the inflammatory response. The loss of strongly adherent lymphocytes may contribute to the lymphopenia of SLE.     

Antibodies to mannose binding lectin in patients with systemic lupus erythematosus

Deficiency of mannose binding lectin (MBL), a C-type lectin with structural similarities to C1q, has been shown to predispose to the development of systemic lupus erythematosus (SLE). Some patients have low serum MBL levels which cannot be explained by either structural gene mutations or promoter polymorphisms. The objective of this study was to detect the presence of autoantibodies against MBL and to evaluate their relationship to serum MBL levels. Anti-MBL antibodies of IgM and IgG classes from consecutive SLE patients (n = 135) and healthy subjects (n = 50) were measured by an in-house ELISA. Using the 90th percentile of controls as a cutoff, more SLE patients [23.7% (32/135)] were found to have IgG anti-MBL antibodies than normal controls [10.0% (5/50)] (P = 0.04). The same trend was observed when ethnicity was taken into account by analysing Caucasians alone (n = 90). IgM anti-MBL antibodies were only found in two SLE patients (2/22, 9.1%) who had no concomitant IgG anti-MBL antibodies. Serum levels of IgG anti-MBL antibodies were found to correlate with serum MBL levels (r = 0.55, P = 0.049). However, the levels of anti-MBL antibodies did not correlate with overall disease activity. Thus the production of anti-MBL antibodies is likely to be a specific antigen-driven process. Its role in lupus pathogenesis remains to be elucidated.     

Sera from patients with systemic lupus erythematosus demonstrate enhanced IgG binding to endothelial cells pretreated with tumour necrosis factor alpha

Fluorescence flow cytometry and indirect immunofluorescence were used to detect circulating IgG antiendothelial cell antibodies (IgG-AECA) in the sera of patients suffering from rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS). Pretreatment of endothelial cells with tumour necrosis factor alpha (TNF), but not with interferon gamma (IFN), increased the IgG binding from sera of some patients with active SLE. In contrast, no change in binding activity to cytokine-stimulated endothelial cells was observed in the RA and PSS sera. The results of this study suggested that the enhanced binding of IgG from the sera of patients with SLE to endothelial cells stimulated with TNF may be due to the ability of this cytokine to increase the expression of potential antigens on the surface of these cells. Hence, TNF may play a role in the immune-mediated vascular damage associated with SLE.     

Decreased capacity to solubilize immune complexes in sera from patients with systemic lupus erythematosus

The capacity to solubilize immune complexes formed in vitro is significantly decreased in patients with systemic lupus erythematosus (SLE). This complement function correlates significantly with serum C3 levels and inversely with the presence of circulating immune complexes. Clinically, patients with a decreased capacity to solubilize complexes show a worse evolution and an increased incidence of renal involvement. In conclusion, the impaired solubilization capacity, related to low complement activity, which is observed in patients with SLE may favor the persistence of immune complexes in tissues.     

Decreased live births in women with systemic lupus erythematosus

Objective

Multiple disease‐related factors may limit the number of children born to women with systemic lupus erythematosus (SLE). We calculated live births in women with SLE and compared this with general population rates.

Methods

We studied women with SLE from a subset of centers participating in the Systemic Lupus International Collaborating Clinics Prospective Inception Cohort Study of SLE. Women diagnosed as having SLE before age 50 years were included. Using age, calendar‐period, and country‐specific general population birth rates, we calculated the standardized incidence ratio (SIR) of observed to expected live births. We also performed a multivariate analysis with the SIR as the dependent variable to explore potential predictors of live births.

Results

A total of 339 women with SLE were studied. The number of live births over the interval (n = 313) was substantially below that which would be expected (n = 479; SIR 0.65, 95% confidence interval [95% CI] 0.58–0.73). In the multivariate analyses, black race/ethnicity (SIR 1.47, 95% CI 1.08–2.00) and being married or living common‐law (SIR 2.04, 95% CI 1.52–2.74) were associated with increased live births (relative to what would be expected). There were trends for fewer live births in women exposed to cyclophosphamide (SIR 0.88, 95% CI 0.56–1.38) and in those with high disease activity (mean SLE Disease Activity Index 2000 update score ≥5; SIR 0.82, 95% CI 0.54–1.25).

Conclusion

Overall, we found that women with SLE have fewer live births compared with the general population. Marital status, race/ethnicity, and possibly clinical factors may mediate this effect.     

Decreased natural killer T-like cells correlated to disease activity in systemic lupus erythematosus

Clinical Rheumatology - To evaluate the absolute numbers and frequencies of natural killer T-like (NKT-like) cells in systemic lupus erythematosus (SLE) and to characterize the possible role of the...     

Brachial endothelial function is impaired in patients with systemic lupus erythematosus

OBJECTIVE: To verify if endothelial function is impaired in pre-menopausal women with systemic lupus erythematosus (SLE) and whether endothelial dysfunction is related to disease duration, cumulative prednisone dose, antimalarial use, anticardiolipin antibody (aCL), hypertension, Raynaud's phenomenon, disease activity score, and vasculitis. METHODS: Using high-resolution ultrasound, we measured the diameter of brachial artery at rest, during reactive hyperemia, and after glyceryl trinitrate (GTN). We compared 69 pre-menopausal female patients with SLE (mean age 29 +/- 8 years) with 35 age and sex-matched controls (mean age 29 +/- 6 years), The mean disease duration was 72 months. RESULTS: There was no significant difference in baseline brachial artery diameter. The flow-mediated dilation (endothelial dependent dilation) was significantly impaired in SLE patients when compared to controls (5.0 +/- 5.0% vs 12.0 +/- 6.0%, p < 0.001), even in the subgroup of patients without coronary artery disease risk factor (4.5 +/- 4.0% vs 12.0 +/- 6.0%, p < 0.001). The GTN induced dilation (endothelial independent dilation) was significantly lower in the aCL positive SLE patients when compared to the controls (11.9 +/- 4.0% vs 16.3 +/- 6.0%, p < 0.05). The endothelium-dependent dilation was not related to disease duration, cumulative prednisone dose, antimalarial use, anticardiolipin antibody, hypertension history, Raynaud's phenomenon, SLE disease activity score or vasculitis. CONCLUSION: This is the first study using brachial artery ultrasound imaging to evaluate endothelium function in SLE. Patients with SLE presented lower flow mediated dilation (endothelium dependent dilation) than sex and age-matched controls, even in patients without traditional cardiovascular risk factors and this may represent an early atherosclerotic process.     

Circulating endothelial cells and vascular injury in systemic lupus erythematosus

In flares of systemic lupus erythematosus (SLE), endothelial cells activated by immune stimuli are potential participants in the inflammatory processes, which contribute to injury. Elevated levels of circulating endothelial cells (CEC) may be a proxy for vascular injury, as demonstrated in patients with sickle cell anemia during acute crises. In active SLE, CEC levels in peripheral blood are elevated (vs healthy controls and correlate with plasma C3a). CEC may reflect widespread unrecognized, ongoing injury despite the absence of clinical stigmata of vasculitis in patients with SLE.     

Decreased platelet serotonin levels in systemic lupus erythematosus

Platelet serotonin levels were measured in 41 patients with systemic lupus erythematosus (SLE) and 36 normal controls. SLE patients had significantly lower mean serotonin levels (243 +/- 131 versus 414 +/- 175 ng/10(9) platelets, P less than 0.001); the lowest levels occurred in those patients with active disease. No differences in mean platelet serotonin levels were found when we compared patients with or without a history of renal disease, thrombocytopenia, or neuropsychiatric involvement. Decreased release of platelet granule constituents, as measured by plasma levels of the alpha-granule protein, beta-thromboglobulin.     

Circulating endothelial cells and vascular injury in systemic lupus erythematosus

In flares of systemic lupus erythematosus (SLE), endothelial cells activated by immune stimuli are potential participants in the inflammatory processes, which contribute to injury. Elevated levels of circulating endothelial cells (CEC) may be a proxy for vascular injury, as demonstrated in patients with sickle cell anemia during acute crises. In active SLE, CEC levels in peripheral blood are elevated (vs healthy controls and correlate with plasma C3a). CEC may reflect widespread unrecognized, ongoing injury despite the absence of clinical stigmata of vasculitis in patients with SLE.     

Decreased expression of interleukin-2 binding molecules (p70/75) in T cells from patients with systemic lupus erythematosus

Using radiolabeled interleukin-2 (IL-2), affinity cross-linking and binding assays revealed that the expression of intermediate-affinity IL-2 binding molecules (p70/75) on freshly prepared T cells from patients with systemic lupus erythematosus (SLE) was significantly decreased in comparison with that in normal subjects. The proliferative response of T cells to high doses of IL-2 was also reduced in patients with SLE. The decreased expression of p70/75 reflects the hyporesponsiveness to IL-2 of T cells in patients with SLE.     

Decreased activity of interleukin-2 inhibitor in plasma of patients with systemic lupus erythematosus

Summary Low levels of plasma interleukin-2 inhibitory activity were found in patients with systemic lupus erythematosus (SLE) compared to normal individuals. The depression of the inhibitory activity was significant in patients with severe and moderate SLE while only a slight decrease was observed in the mild form of the disease.     

系统性红斑狼疮的心脏损害

目的：探讨系统性红斑狼疮（SLE）的心脏受累表现，并分析年龄、性别，病程及抗心磷脂抗体（ACL）与SLE心脏损害的相关性。方法：回顾性总结分析1998年9月至2000年8月我院诊断SLE的入院病人272例，结果：272例SLE病人中145例（53．3％）具有心脏损害，10例病人具有心脏病相关症状（6．7％），心脏损害包括心电图（ECG）ST－T异常61例（42．1％），心包积液60例（41．4％），肺动脉高压23例（15．9％），心肌损害22例（15．2％），心律失常20例（13．8％），瓣膜病19例（13．1％），左心耳血栓1例（0．6％）。心脏损害组与无心脏损害组之间年龄，性别差异无差异性（P＞0．05，病程差异有显著性（P＜0．01），ACL阳性组与阴性组瓣膜损害发生率差异有显著性（P＜0．01），结论：SLE可以累及心脏各个部分，其中以ECC ST－T缺血性改变和心包受累最为常见。SLE累及心脏时多属无症状型，SLE心脏损害与病程有关，抗心磷脂抗休与心脏瓣膜损害关系密切。     

Multipotent hemopoietic progenitor cells in patients with systemic lupus erythematosus

Hematologic abnormalities in patients with systemic lupus erythematosus (SLE) were studied before treatment, using an in vitro bone marrow progenitor cell assay. In 10 patients with SLE, there was a decrease in the number of multipotent hemopoietic colonies. Multipotent colony formation was suppressed by the addition of T cells from the patients with SLE. The culture supernatant of phytohemagglutinin stimulated SLE leukocytes had diminished activity to support the multipotent colony formation. These results suggest that the hematologic abnormalities in SLE occur at the multipotent stem cell level. The T cell mediated suppression of hemopoietic progenitor cells and the diminished activity of humoral factors released from SLE leukocytes may play some role in the pathogenesis of hematologic abnormalities in SLE.     

Decreased arachidonic acid release in peripheral blood monocytes of patients with systemic lupus erythematosus

OBJECTIVE: To investigate the release of arachidonic acid (AA) in unfractionated peripheral blood mononuclear cells (PBMC), separated monocytes and T lymphocytes of patients with systemic lupus erythematosus (SLE). METHODS: AA release was measured in cells from 56 patients with SLE and from 48 controls. Of the 56 patients with SLE, 38 were receiving glucocorticosteroids and 18 were not. [3H]AA was incorporated into the membranes of PBMC and purified subsets of monocytes and T lymphocytes. The release of [3H]AA was measured both in nonstimulated cells cultured for 24 h and in cell cultures stimulated by phorbol ester (PMA) and Ca2+ ionophore for 4 h. RESULTS: In the PBMC of SLE patients not taking glucocorticosteroids, the release of AA was decreased in both stimulated and nonstimulated cells. There was a decrease of AA production in monocytes but not in T lymphocytes. This phenomenon could be observed in the active and inactive phases of the disease. CONCLUSION: A defect in AA production may exist in the peripheral monocytes of patients with SLE, resulting in decreased release of AA in patients not receiving glucocorticosteroid therapy.     

Decreased serum level of IL-21 in new-onset systemic lupus erythematosus patients

This study aims to investigate the serum IL-21 levels in systemic lupus erythematosus (SLE) and its relations with clinical and laboratory features. Fifty-seven patients with SLE and 30 healthy volunteers were recruited in the current study. Serum IL-21 levels were detected by enzyme-linked immunosorbent assay. Statistical analyses were performed by SPSS 10.01. Results showed that IL-21 levels were significantly decreased in the serum of patients with SLE compared with controls (P = 0.026). There was no significant difference regarding serum IL-21 level between SLE patients with nephritis and those without nephritis (P = 0.066); no significant difference was found between less active SLE and more active SLE (P = 0.588). The presence of anemia was associated with low serum IL-21 levels (P = 0.030) in SLE patients. In summary, decreased serum level of IL-21 and its association with anemia indicate a possible role of IL-21 in human SLE. However, further studies are needed to confirm this preliminary results.     

Impaired endothelial function in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) patients suffer from excess cardiac deaths due to accelerated atherosclerosis. Endothelial dysfunction is a marker of early atherosclerosis. We tested the hypothesis that SLE patients have impaired endothelial function and assessed the relationship between endothelial function and clinical outcome over the subsequent five years. Thirty-six female SLE patients were compared with 22 healthy age and sex matched controls. Endothelial dependent vasodilatation (EDD) was assessed at the brachial artery in response to shear stress. Endothelium-independent dilatation induced by glyceryl trinitrate was also measured. Patients were followed for up to five years and the development of damage in the cardiovascular and other systems recorded. SLE patients showed significantly impaired endothelial function (median EDD 5.6%, IQR 3.1-7.2%) compared with healthy controls (median EDD 8.0%, IQR 6.3-9.3%; P = 0.001). Endothelium independent dilatation did not differ between the two groups. Endothelial function was significantly worse in postmenopausal compared with premenopausal women (median EDD 6.6%, IQR 3.9-7.8% versus 3.1%, IQR 2.6-5.1%; P = 0.016). Total cholesterol was inversely correlated with endothelial function in SLE patients (Spearman correlation r = -0.422, P = 0.025). There was no relationship between endothelial function and the development of damage in any organ system, including the cardiovascular system during patient follow-up. Patients with SLE have impaired endothelial Lupus (2007) 16, 84-88.     

Clinical significance of selected endothelial activation markers in patients with systemic lupus erythematosus

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease in which immunologically mediated vascular endothelial cell activation is regarded as a potential pathophysiological mechanism of systemic organ damage. We investigated selected endothelial cell activation markers in serum of patients with SLE and their relationships with systemic organ manifestations and disease activity. METHODS: Serum levels of endothelin-1 (ET-1), soluble E-selectin, and thrombomodulin (sTM) were determined by ELISA in 76 SLE patients and in 34 healthy controls. RESULTS: Higher serum concentrations of ET-1, sE-selectin (p < 0.05), and sTM (p < 0.001) were observed in SLE patients in comparison with controls. Significant differences of ET-1, (p < 0.01), sTM (p < 0.001), and sE-selectin serum concentrations (p < 0.01) were found between SLE patients with systemic involvement and controls. Patients with organ manifestations (n = 34) showed significantly higher serum levels of ET-1 than patients without systemic involvement (n = 42) (p < 0.05). Comparison between patients with active and inactive SLE according to SLE Disease Activity Index (SLEDAI) score showed significantly higher concentration of ET-1 in the sera of patients with active SLE compared with inactive patients and the controls (p < 0.001). CONCLUSION: Our findings suggest that the elevated serum concentrations of ET-1, sTM, and sE-selectin reflect persisting endothelial cell activation in SLE, and point to an important role of ET-1 in the pathogenesis of internal organ involvement. Moreover, elevated ET-1 concentrations are related to disease activity, suggesting a key role of endothelial cell activation in systemic manifestations in SLE patients.