Selected Systemic Lupus Erythematosus Patients Research Articles

Elevated plasma interleukin-37 levels in systemic lupus erythematosus patients.

This study aims to evaluate the plasma interleukin (IL)-37 levels in systemic lupus erythematosus (SLE) patients, as well as its association with major clinical and laboratory features. Ninety consecutively selected SLE patients and 78 community-based healthy controls were recruited. Plasma IL-37 levels were detected by enzyme-linked immunosorbent assay (ELISA). The major clinical and laboratory data of SLE patients were also recorded. The results showed that IL-37 level was significantly higher in the plasma of patients with SLE compared with controls (p = 0.028). The correlation of plasma IL-37 levels with major clinical and laboratory data of SLE patients was also analyzed, and the results showed that anti-Sm and anti-RNP were negatively associated with plasma IL-37 levels of SLE patients, while C3 was positively associated with plasma IL-37 levels of SLE patients. No significant associations of IL-37 with other clinical and laboratory parameters were observed (all p > 0.05). In conclusion, elevated plasma IL-37 level and its associations with anti-Sm, anti-RNP and C3 in SLE patients suggest that IL-37 may be implicated in this disease.

Impaired receptor editing and heterozygous RAG2 mutation in a patient with systemic lupus erythematosus and erosive arthritis

Impaired receptor editing and heterozygous RAG2 mutation in a patient with systemic lupus erythematosus and erosive arthritis

Clinical analysis of 56 patients with rhupus syndrome: manifestations and comparisons with systemic lupus erythematosus: a retrospective case-control study.

To investigate the clinical features of Rhupus syndrome, we retrospectively reviewed the medical records of 56 patients with Rhupus who were hospitalized at the Peking Union Medical College Hospital, Beijing, China, between January 2000 and March 2013. We analyzed the clinical manifestations of Rhupus syndrome and compared these with a control group of 160 randomly selected systemic lupus erythematosus (SLE) patients without coexisting rheumatoid arthritis (RA). In our center, 1.30% (56/4301) of hospitalized SLE patients had Rhupus syndrome. The median disease duration was 8.0 years and 83.9% had RA onset. All Rhupus patients showed radiological erosion in the joints. Compared with the control group, Rhupus patients had a longer disease duration, higher prevalence of anticyclic citrullinated peptide antibody and rheumatoid factor, higher incidence of symmetrical polyarthritis with more joint deformities and rheumatic nodules, and increased erythrocyte sediment rate and c-reactive protein levels (P < 0.005). In addition, a lower SLE disease activity index and incidences of malar rash, hemolytic anemia, renal and neurological involvement (P < 0.005), and hypocomplementemia (P < 0.05) was observed in the Rhupus group.Rhupus syndrome is rare in SLE patients. Most Rhupus patients had RA onset and a distinctive clinical profile characterized by more severe RA-associated and mild SLE-associated damage. Specific autoantibodies and imaging findings could be helpful for making accurate Rhupus diagnoses.

AB0188 Atherosclerosis and Cardiovascular Disease in Systemic Lupus Erythematosus. Effects of Statins Treatment

BackgroundStatins may have beneficial vascular effects in systemic lupus erythematosus (SLE) beyond their cholesterol-lowering action, although involved mechanisms remain incompletely understoodObjectivesTo investigate the potential mechanisms participating in the efficacy of...

Identification of rare anti-phospholipid/protein co-factor autoantibodies in patients with systemic lupus erythematosus

Lupus anticoagulant (LA) and β2-glikoprotein I (b2GPI) dependent anti-cardiolipin (aCL) are part of the diagnostic criteria both of systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). Anti-phospholipid antibodies (aPL) may also bind to other phospholipids and/or protein co-factors. In the present study, besides aCL and anti-b2GPI, antibodies directed against phosphatidylserine, prothrombin (PT) and annexin V (aANX) were measured in 85 randomly selected SLE patients, 14 suffering from secondary APS. LA was detected by hemostasis tests. Correlations were determined between rare aPLs and clinical manifestations, including thrombotic events. Anti-cardiolipin IgG was positive in 14 patients, aCL IgM in 8, anti-b2GPI IgG in 4 and IgM in 5 patients. LA was detected in nine cases. Seven patients were positive for anti-phosphatidylserine (aPS) IgG, nine for aPS IgM, while anti-PT (aPT) IgG was positive in nine cases. aPT IgM and anti-aANX were negative in all patients. Correlation was found between aPS and aCL antibodies. The frequency and concentration of rare anti-phospholipid/co-factor antibodies was higher in patients with secondary APS. The presence of such rare aPLs cumulated in APS patients, their presence increased the frequency of thrombotic events in the entire study population, furthermore in patients positive for LA or aCL. Rare anti-phospholipid/co-factor antibodies were found in 12% of an un-selected lupus patient population. Their presence was more frequent in patients with secondary APS, and further increased the risk of thrombotic complications.

High prevalence of subclinical cardiovascular abnormalities in patients with systemic lupus erythematosus in spite of a very low clinical damage index

Background and aim To evaluate the prevalence of subclinical cardiovascular (CV) abnormalities in systemic lupus erythematosus (SLE) stratified according to SLE-related organ damage using the Systemic Lupus International Collaborating Clinics (SLICC) damage index. Methods and results We selected SLE patients without clinically overt CV events ( n = 45, 56% with SLICC = 0, 44% with SLICC = 1–4). CV evaluation was performed using cardiac and vascular echo-Doppler techniques. Post-ischemic flow-mediated dilation (FMD) over nitroglycerine-mediated dilation (NMD) of the brachial artery <0.70 defined endothelial dysfunction. The prevalence of preclinical CV abnormalities (CVAbn, including at least one of the following—carotid atherosclerosis, left ventricular (LV) hypertrophy, low arterial compliance, LV wall motion abnormalities, aortic regurgitation, FMD/NMD < 0.70)—was 64% (16/25) in patients with SLICC = 0 and 80% (16/20) in those with SLICC > 0 ( p = not significant (NS)). In particular, the prevalence of carotid atherosclerosis (28% vs. 16%), of LV hypertrophy (12% vs. 6%) and of LV wall motion abnormalities (15% vs. 12%), of low global arterial compliance (18% vs. 10%), prevalence of aortic regurgitation (30% vs. 18%) and/or aortic valve fibrosclerosis (10% vs. 8%), FMD < 10% (14 ± 5% vs. 14% ± 6) and prevalence of FMD/NMD < 0.70 (53% vs. 52%) were comparable in SLE patients with SLICC > 0 and in those with SLICC = 0 (all p = NS). Of the SLE patients without carotid atherosclerosis, LV hypertrophy, low arterial compliance, LV wall motion abnormalities and aortic regurgitation ( n = 17), endothelial dysfunction was detected in 50% of those with SLICC = 0 (6/12) and in 40% of those with SLICC > 0 (2/5, p = NS). Conclusions SLE patients with SLICC = 0 often have an elevated CV risk profile due to subclinical manifestations of CV disease detectable by cardiac and vascular echo-Doppler evaluations.

Variable Increased Expression of Program Death‐1 and Program Death‐1 Ligands on Peripheral Mononuclear Cells Is Not Impaired in Patients with Systemic Lupus Erythematosus

Programmed death-1 (PD-1) was shown to deliver an inhibitory signal after binding to its ligands, PD-L1 (B7-H1) or PD-L2 (B7-DC). Recently, up-regulated expression of PD-1 molecule and/or its ligands was demonstrated in human diseases including rheumatoid arthritis and inflammatory colitis. The study aimed to investigate the expression and function of PD-1 and PD-1 ligands on circulating T cells, B cells and monocytes from patient with systemic lupus erythematosus (SLE). The results showed that patients with SLE had significantly increased percentages of PD-1-expressing CD3+T cells and CD19+B cells, PD-L1-expressing CD19+B cells and PD-L2-expressing CD14+B monocytes. In selected SLE patients and normal subjects, functional study of PD-1/ PD-1 ligands pathway on the production of cytokines by stimulated PBMC was examined. Blockages of PD-1 or PD-1 ligands substantially increased the production of IL-2, IFN-γ and IL-10, the amplitude of increase roughly ranged from one to three times. There were no significant differences of the enhancing effects on cytokine production by blockage of PD-1/PDL pathway between SLE patients and normal subjects. The study indicates that there are no intrinsically defective expression and function of PD-1 and PD-1 ligands on PBMC in patients with SLE.

Indications for plasma exchange in systemic lupus erythematosus in 2005

Plasma exchange can remove putative pathogenic autoantibodies and circulating immune complexes from the blood of patients with systemic lupus erythematosus (SLE). However, their efficacy has only been supported by noncontrolled and/or retrospective studies. Nonetheless, PE may still be of relevance in some selected SLE patients and as adjunctive therapy, in combination with corticosteroids (CS) and other immunosuppressant(s). We review herein the principal historical steps of the use of plasma exchange to treat SLE, based upon the main trials and case reports that have highlighted its most pertinent indications. Acute life-threatening manifestations and severe therapy-resistant manifestations, like refractory SLE renal disease, diffuse alveolar hemorrhage, neuropsychiatric SLE, thrombotic thrombocytopenic purpura, catastrophic antiphospholipid syndrome, hyperviscosity syndrome and cryoglobulinemia, are the indications for which plasma exchange might have a beneficial therapeutic role. Although few SLE patients undergo plasma exchange each year nowadays (10-20 per year in France), adverse events are very rare and recent advances in plasma exchange technologies, like immunoadsorption, might, in the future, counterbalance their cost and broaden their place in the therapeutic armamentarium for SLE.

Increased serum aminotransferases associated with anti-mitochondrial antibodies in systemic lupus erythematosus patients with autoimmune liver disease

Background Serum aminotransferase activities are increased in many liver diseases, but the causes for the elevation might be difficult to determine. Whether the elevation of aminotransferases correlates with anti-mitochondrial antibodies (AMA) in systemic lupus erythematosus (SLE) patients with autoimmune liver disease deserves further consideration. Methods A meticulous review was done in a large SLE cohort searching for laboratory features of the presence of AMA. Forty-eight hospitalized SLE patients with AMA and 60 randomly selected SLE patients without AMA as a matched case control were enrolled into the retrospective study. Laboratory data were collected, analyzed and compared in SLE patients with and without AMA. Results Serum activities of aminotransferases were significantly increased in the 48 SLE patients with AMA compared with the 60 subjects without AMA. Meanwhile, we found a positive correlation between serum AMA titers and serum aminotransferase activities. Conclusion Although much remains to be learned about the pathogenesis of autoimmune liver disease associated with AMA, it is possible to suggest that AMA might contribute to the elevation of aminotransferases in SLE patients with the progressive disease.

SLE, atherosclerosis and cardiovascular disease

Atherosclerosis is an inflammatory disease and the major cause of cardiovascular disease (CVD) in general. Atherosclerotic plaques are characterized by the presence of activated immune competent cells, but antigens and underlying mechanisms causing this immune activation are not well defined. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are important clinical problems but may in addition also shed light on how immune reactions are related to premature atherosclerosis and atherothrombosis. A combination of traditional and nontraditional risk factors, including dyslipidaemia (and to a varying degree hypertension, diabetes and smoking), inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. Premature atherosclerosis in some form leading to atherothrombosis is likely to be a major underlying mechanism, though distinctive features if any, of SLE-related atherosclerosis when compared with 'normal' atherosclerosis are not clear. One interesting possibility is that factors such as inflammation or aPL make atherosclerotic lesions in autoimmune disease more prone to rupture than in 'normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients remains to be demonstrated. Treatment of SLE patients should also include a close monitoring of traditional risk factors for CVD. In addition, attention should also be paid to nontraditional risk factors such as inflammation and SLE-related factors such as aPL. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation and immune reactions present in atherosclerotic lesions.

Conjugates or dsDNA linked to human gammaglobulin inhibit anti-dsDNA antibodies in vitro.

Previous studies have shown that both nucleosides and oligonucleotides linked to isologous gammaglobulin suppress anti-nucleic acid antibody production both in vivo and in vitro. The aim of this study was to determine whether one can make a DNA-human gammaglobulin (HGG) conjugate which can inhibit anti-double stranded DNA (dsDNA) antibodies obtained from a heterogeneous population of systemic lupus erythematosus (SLE) sera. To do so, we constructed conjugates of sonicated dsDNA fragments of 100-400 base pairs covalently linked to HGG with varying degrees of substitution of DNA:HGG. An ELISA inhibition assay was used to determine which conjugate best inhibits the binding of anti-dsDNA antibodies. Conjugate 2, prepared with monomeric HGG (150 kD) with a high degree of substitution (3.72 DNA:HGG) inhibited the binding of anti-dsDNA antibodies from 27 of 31 SLE sera. In addition, this conjugate inhibited the spontaneous formation of anti-dsDNA in vitro by cultured lymphoid cells from selected SLE patients. Together, this data suggests that a 'generic' tolerogen may provide an antigen specific therapy for SLE.

Activation of the complement pathway: comparison of normal pregnancy, preeclampsia, and systemic lupus erythematosus during pregnancy.

To evaluate a flare of systemic lupus erythematosus (SLE) during pregnancy and to differentiate it from diseases of pregnancy, serological parameters are often utilized. However, there are conflicting reports regarding the merit of conventional measurements of complement and activation products. While in normal pregnancy the levels of serum C3, C4, and CH50 gradually rise, a decline in these levels occurs during the course of pregnancy in selected SLE patients. There is controversy regarding whether such falls represent decreases in the overall synthesis of complement or activation, the former theory being supported by a report of normal levels of the C1s-C1 inhibitor complex. During normal pregnancies, increases of complement split products, such as plasma C3a, may occur, and these correlate positively with elevations of C3. In pregnancies complicated by lupus, increases of C3a are often accompanied by a decline in total C3 and CH50. In a minority of non-SLE patients, preeclampsia has been associated with elevations of a variety of complement split products. Ba, C3a, C4d, SC5b-9, indicating activation of both the classical and alternative pathways. The CH50 levels tend to remain normal in these patients. In contrast, elevations of complement split products frequently accompany disease flares in patients with SLE. A high ratio of CH50/Ba may differentiate patients with preeclampsia from those with active SLE. A decline in conventional measures of C3, C4, or CH50 which is accompanied by elevations of complement split products appears to differentiate a lupus flare from non-SLE diseases of pregnancy.

Mechanisms of action of intravenous immunoglobulin therapy and potential use in autoimmune connective tissue diseases

It has been almost 10 years since the observations on the efficacy of intravenous immunoglobulin (IVIG) in patients with autoimmune thrombocytopenic purpura. Over the next decade, IVIG was used in other types of autoimmune diseases. Much work has also been done on gaining a better understanding of the mechanism(s) by which IVIG exerts its effects in these autoimmune diseases. This review examines the proposed mechanisms of action of IVIG and establishes a rationale for the use of this type of therapy in systemic lupus erythematosus (SLE) and other autoimmune connective tissue disorders. Currently, only anecdotal reports are available on the treatment of SLE with IVIG. Nevertheless, studies thus far suggest that IVIG may be useful in selected SLE patients with cytopenias and cutaneous vasculitis and may have a steroid-sparing effect in patients with SLE and juvenile rheumatoid arthritis. In SLE patients with renal disease, it should be used cautiously because some patients have worsening of their renal function with IVIG infusions. These preliminary experiences suggest that multicenter controlled trials on the therapeutic use of IVIG in SLE and other connective tissue disorders would be important.