Lupus Disease Activity Research Articles

Association between serum trace element concentrations and the disease activity of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex, incompletely understood, etiology. Several genetic and environmental factors are suspected to be involved in its aetiology. Oxidative stress may be implicated in the pathogenesis of SLE and may be affected by trace element status. Zinc (Zn), copper (Cu) and selenium (Se) are essential components of several anti-oxidative enzymes and are also involved in several immune functions. The current study aimed to assess the relationship between serum concentrations of these trace elements and the clinical disease activity of SLE assessed using the SLE disease activity index (SLEDAI). Serum concentrations of albumin (Alb) (p = 0.001), Se (p = 0.001), Zn (p = 0.001) and the Zn to Cu ratio (Zn/Cu R) (p = 0.001) were lower in patients with SLE than the age- and sex-matched healthy controls. However, only Alb (p = 0.001) and Cu (p = 0.03) were negatively correlated with disease activity, which was supported by regression analysis. In summary, lower serum values of Alb, Zn, Se and Zn/Cu R were found in SLE patients compared with healthy controls; however, in addition to serum Alb concentrations, serum Cu concentrations were also negatively correlated with lupus disease activity.

Side effects unrelated to disease activity and acceptability of highly effective contraceptive methods in women with systemic lupus erythematosus: a randomized, clinical trial

ObjectivesTo assess the side effects unrelated to disease activity and the acceptability of combined oral contraceptives (COCs), progestin-only pills (POPs) and copper-releasing intrauterine devices (IUDs) in women with systemic lupus erythematosus (SLE). Study designA randomized clinical trial including 162 women with SLE, assigned to COC (n=54), POP (n=54) or IUD (n=54). Follow-up visits were conducted after 1, 2, 3, 6, 9 and 12 months of treatment to monitor the presence of symptoms, changes in body weight and blood pressure as well as the development of health problems other than those relating to lupus. Reasons for discontinuation and satisfaction with the use of the assigned method were recorded at the end of treatment. Statistical analysis included descriptive statistics, repeated measure analyses and Kaplan–Meier curves. ResultsSignificantly different discontinuation rates due to any reason [35%, 55%, 29% (p<0.01)] or nonmedical reasons [(11%, 31%, 4% (p<0.05)] were observed among the COC, POP and IUD groups. Nausea was most frequent among COC users, dysmenorrhea among IUD users and acne and hirsutism among POP users. Mean blood pressures remained unchanged. Mild increases in body weight were observed over time in all treatment groups. Most women were satisfied with the use of the assigned contraceptive method. ConclusionsOral contraceptives and IUD are acceptable birth control methods for patients with lupus, when counseling and specialized health attention are provided; however, the acceptability of POP appears to be inferior. Side effects unrelated to lupus disease activity are not frequent reasons to discontinue the contraceptive methods. ImplicationsThis study delves into an area that has not been explored among patients with lupus. Our findings on the associated side effects and reasons for discontinuing COCs, POPs or copper-bearing IUDs may be useful in improving contraceptive counseling for women with lupus. Furthermore, they also heighten our knowledge on the reasons that may preclude the widespread use of effective contraceptives among lupus patients.

Lupus flares in two established end-stage renal disease patients with on-line hemodiafiltration during pregnancy – case series

Many patients with established end-stage renal disease on maintenance dialysis as a result of lupus nephritis are young females in their reproductive years. We report two such patients dialyzed with on-line hemodiafiltration who developed reactivation of lupus disease activity only when they conceived after initial systemic lupus erythematosus burnout. We believe that the flare was triggered by both efficient dialysis and hormonal changes during pregnancy. The flares were treated with oral corticosteroids with an excellent response. Both patients had live births but delivered preterm.

Risk Factors for Neuropsychiatric Manifestations in Children With Systemic Lupus Erythematosus: Case-Control Study

BackgroundNeuropsychiatric symptoms in children with systemic lupus erythematosus cause high morbidity and disability. This study analyzed risk factors associated with neuropsychiatric presentation in patients with systemic lupus erythematosus aged <18 years. MethodsA case-control study was performed. Medical record information of patients with a diagnosis of systemic lupus erythematosus who were hospitalized with or without neuropsychiatric symptoms was collected between March 2007 and January 2012. Clinical variables, laboratory examinations, neuroimages, and disease activity (Systemic Erythematosus Lupus Disease Activity Index) and damage (Systemic Lupus International Collaborating Clinics) indices were analyzed. ResultsA total of 90 patients were selected, 30 with neuropsychiatric symptoms. The patients' average age was 12.2 years. The most common neuropsychiatric symptoms were seizures, migraine, and depression. The average Systemic Erythematosus Lupus Disease Activity Index was 19.86 (S.D. 10.83) and the average Systemic Lupus International Collaborating Clinics index was 2.02 (S.D. 2.43), with higher values in patients with neuropsychiatric symptoms (P = 0.001). The levels of complement C3 and C4 were significantly higher in patients with a neuropsychiatric disorder (P = 0.003). Lupus anticoagulant was found in 51.5% of patients with neuropsychiatric symptoms (odds ratio, 3.7; 95% confidence interval, 1.3-10.0). Immunosuppression with azathioprine, rituximab, or cyclophosphamide delayed the time to neuropsychiatric systemic lupus erythematosus development by 18.5 months (95% confidence interval, 10.6-26.5) compared to patients who did not receive these agents. ConclusionsThe presence of lupus anticoagulant was a risk factor in our patients. The use of immunosuppressants, such as cyclophosphamide, rituximab, and azathioprine, delayed the presentation of neuropsychiatric manifestations of lupus.

Influence of Pretransplantation Dialysis Time and Lupus Activity on Outcome of Kidney Transplantation in Systemic Lupus Erythematosus

BackgroundKidney transplantation (KT) has better outcome compared with dialysis in lupus patients. The duration lupus patients need to wait before KT remains debatable, especially in patients with lupus activity. We analyzed a renal transplantation database to elucidate if pretransplantation dialysis (PTD) time and lupus activity affected outcome. MethodsFrom 1984 to 2012, 31 Chinese lupus nephritis patients underwent KT at our hospital. The lupus activity was defined as nonrenal systemic lupus erythematosus disease activity index (SLE-DAI) score. Biopsy-proven acute rejection/recurrent lupus nephritis (RLN) were recorded. Chronic allograft dysfunction (CAD) was defined as doubling of serum creatinine level. Graft failure was defined as return to dialysis. We calculated relative hazard ratios (HR) with 95% confidence intervals (CI) from Cox proportional-hazards regression models. ResultsIn total, 31 lupus patients with KT (7 men and 24 women), with a mean age of 35.3 years at transplantation, were enrolled in this study. The mean follow-up duration was 8.2 years. The mean PTD time was 3.3 years. Both PTD time and lupus activity before transplantation had no effect on CAD and graft failure. Longer PTD time was associated with more acute rejection (HR = 1.20; 95% CI, 1.02–1.41). Also, maximal lupus activity after transplantation was associated with more CAD (HR = 6.44; 95% CI, 1.36–30.57). ConclusionFor Chinese lupus patients with KT, longer PTD time was associated with worse outcome. Patients should undergo KT immediately if a kidney is available for donation, even with active lupus disease. It is necessary to monitor lupus activity after transplantation due to its effect on outcome.

Anti-nucleosome antibodies: A potential surrogate marker for renal affection in lupus patients with insignificant proteinuria

BackgroundLupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE). Clinical renal involvement is present in about two-thirds of lupus patients and more patients would have morphologic evidence of renal disease without clinical manifestations. Aim of the workTo investigate serum anti-nucleosome antibodies role as a biomarker for renal affection in lupus patients with insignificant proteinuria. Patients and methodsTwenty-four lupus patients with proteinuria <500mg/d (group-A), 30 patients with established lupus nephritis (group-B) and 15 controls were included. Systemic lupus erythematosis disease activity index (SLEDAI), anti-nucleosome, anti-dsDNA antibodies and renal biopsy were assessed in all patients. ResultsSerum anti-nucleosome antibodies were significantly higher in all lupus patients than control (P<0.001) and showed significant positive correlation with SLEDAI score. SLE patients with positive anti-dsDNA antibody had more active disease by SLEDAI and higher levels of anti-nucleosome antibodies than those with negative anti-dsDNA antibodies. In both studied groups, serum anti-nucleosome antibodies were significantly higher in patients with class II LN than the control and in class III LN than in class II LN (P<0.001). Yet, in both groups, anti-nucleosome was not useful in differentiating active from chronic renal affection. ConclusionSerum levels of anti-nucleosome antibodies are associated with active lupus disease and correlate with the degree of renal affection. In patients with insignificant proteinuria, serum levels of anti-nucleosome antibodies were elevated and were related to the degree of renal affection. Anti-nucleosome antibodies may be used as a surrogate marker for early renal affection in lupus patients with insignificant proteinuria.

Study of insulin resistance in patients with systemic lupus erythematosus and rheumatoid arthritis

ObjectiveThe aim of the study was to study insulin resistance (IR) and pancreatic b-cell function in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and their relationship with disease activity.BackgroundIR is an important contributor to the increased cardiovascular risk attributed to the metabolic syndrome, a constellation of cardiovascular risk factors that includes central obesity, dyslipidemia, hypertension, and disturbed glucose metabolism, in patients with RA or SLE.Patients and methodsThe study included 35 SLE and 35 RA patients and 20 controls. Disease activity was assessed by Systemic Lupus Activity Measure score and Disease Activity Score-28. BMI, C-reactive protein, erythrocyte sedimentation rate, lipid profile, fasting glucose and insulin, and c-peptide were determined. The homeostasis model of assessment (HOMA) was used to evaluate IR and secretion.ResultsSLE patients had high-grade systemic inflammation, IR, and secretion compared with controls (P < 0.05). RA patients revealed high-grade systemic inflammation, IR, and secretion compared with controls (P < 0.001). Active SLE and RA patients were more insulin resistant than nonactive patients.ConclusionThe present study demonstrated that both SLE and RA patients had a higher IR and abnormal insulin secretion than age-matched apparently healthy controls. This conclusion was based on the measurement of fasting insulin concentration, HOMA IR, and HOMA b-cells. IR and abnormal insulin secretion were associated with markers for inflammation (erythrocyte sedimentation rate and C-reactive protein) and disease activity indices (Systemic Lupus Activity Measure and Disease Activity Score-28). Higher IR and abnormal insulin secretion were found in RA patients in comparison with SLE patients.

Relationship between Serum Level of Interleukin-2 in Patients with Systemic Lupus Erythematosus and Disease Activity in Comparison with Control Group.

Despite the large number of surveys, there are not any validated biomarkers for SLE disease activity till now. This study aimed to evaluate the relationship between serum level of IL-2 in patients with SLE and disease activity in comparison with control group. In this case-control study, 73 patients with lupus and 73 healthy subjects referred to the rheumatology clinic of 5 Azar Hospital in Gorgan (North of Iran).They were studied via convenience sampling during 2011-2012. Blood samples were taken from both groups and serum levels of interleukin -2 measured by Avi Bion Human IL-2 ELISA kit. Serum Level of IL-2 greater than 15 pg/ml defined positive and lesser than this amount defined negative. Disease activity evaluated with SLE disease activity index. Score greater than or equal to three or four defined as active disease. Data analysis conducted by SPSS software (version 16) and by using descriptive statistics and statistical tests. Serum level of IL-2 was positive in 45.2% of sample studied and negative in 54.8% in case group, while in control group, serum level of IL-2 only in 11% of sample studied was positive and in 89% was negative. Statistical analysis indicated a significant relationship between serum level of IL-2 and the SLE disease activity index (p=0.025). This study showed the relationship between serum levels of IL-2 and disease activity, so this biomarker can be used as a clinical indicator for assessing disease activity in patients with SLE.

Optimal determination of Physician Global Assessment of lupus disease activity: a pilot study

Optimal determination of Physician Global Assessment of lupus disease activity: a pilot study

PReS-FINAL-2280: Lupus disease activity in a pediatric Colombian cohort with systemic lupus erytematosus

Systemic Lupus Erythematosus (SLE) is disease which may have severe and variable activity in the pediatric population.

Clinical Features and Outcomes of Posterior Reversible Encephalopathy Syndrome in Patients With Systemic Lupus Erythematosus

To analyze the clinical features and outcomes of patients with posterior reversible encephalopathy syndrome(PRES), the risk factors of PRES-related intracranial hemorrhage (ICH), and all-cause mortality in patients with systemic lupus erythematosus (SLE). Twenty-six episodes of PRES were identified in 23 SLE patients, using an electronic medical records database of 3,746 SLE patients. The prevalence of PRES was 0.69% among SLE patients. The scores of the SLE Disease Activity Index without neurologic descriptors (SLEDAI-N) were significantly elevated from baseline for a mean of 3.3 during PRES (P = 0.009). Rapidly deteriorating renal function, pulmonary hemorrhage, thrombotic microangiopathy, macrophage activation syndrome, or multiple organ dysfunction syndrome appeared during 65.4% of episodes. In 16 episodes, patients completely recovered from PRES-related symptoms within a median of 7 days. Visual impairment was reversed within 2 days in 8 of 15 patients, but impairment in other patients was protracted for up to 4 months, especially when ICH was present. Hypoalbuminemia (<20 gm/liter; odds ratio [OR] 30, 95% confidence interval [95% CI] 2.04–441.84) and thrombocytopenia (<30,000/mm(3); OR 21, 95% CI 1.27–346.93) were risk factors for PRES-related ICH. Patients with SLEDAI-N scores >18 during a PRES attack had significantly higher mortality rates than did patients with SLEDAI-N scores ≤18 (P = 0.009 by log rank test). PRES frequently occurs during active SLE with multiple complications. Hypoalbuminemia and thrombocytopenia may contribute to PRES-related ICH. The extra neurologic disease activity of lupus during PRES may influence the mortality rate of SLE patients.

Pulmonary arterial hypertension in SLE: what do we know?

Pulmonary hypertension (PH) can occur at any time during the course of systemic lupus erythematosus (SLE), and can be independent of lupus disease activity in other systems. The pathogenesis of PH in SLE can be multifactorial, but pulmonary arterial hypertension (PAH) is the commonest cause of PH in SLE. The international PH registries have published that approximately 15% of connective tissue disease-associated PH is lupus related in their cohorts. As the symptoms of PH in SLE can be mild and non-specific in early stages, an increasing awareness of this devastating complication is essential for early diagnosis. Echocardiographic evaluation of several right heart variables in addition to systolic pulmonary artery pressure estimation reduces false positive rates for PH detection. Antiphospholipid antibodies may predict SLE-PAH. Prompt treatment of PAH with newer PAH therapy as well as immunosuppression can reduce morbidity and prolong survival. The survival in SLE-associated PAH is better compared with systemic sclerosis-associated PH but worse than idiopathic PAH. Pregnancy in SLE-PAH can result in a fatal outcome, especially in severe and poorly controlled PH at onset.

Splenectomy in Systemic Lupus Erythematosus with Refractory Thrombocytopenia: Efficacy for Thrombocytopenia and Effects on Lupus Disease Activities

The precise role of splenectomy in the treatment of refractory thrombocytopenia associated with systemic lupus erythematosus (SLE) remains a matter of debate. We retrospectively investigated the efficacy of splenectomy in 10 SLE patients who received splenectomy for thrombocytopenia and compared their lupus disease activity before and after operation. Our study showed that the response of thrombocytopenia to splenectomy achieved complete remission in 5 (50%) patients and partial improvement in 3 (30%) patients and the response sustained in the long-term follow-up period. However, compared with disease activity prior to splenectomy, we observed that lupus flare occurred in 5 (50%) patients at 6 months, and in another 4 (40%) patients at 12 months after operation. Kidney was the most frequently affect organ in flare. Surprisingly, among the 10 patients, two developed typical rheumatoid arthritis later. Thus we concluded that splenectomy was safe and effective in the treatment of refractory thrombocytopenia in SLE. Physician should be alert to disease flare and the development of rheumatoid arthritis in the post operative course.

Reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes and normal CD14 soluble levels in juvenile systemic lupus erythematosus

In order to evaluate Fas and Bcl-2 expressions in CD14+ monocytes, to measure soluble CD14 serum levels and to analyze the relationships with lupus nephritis and disease activity, we enrolled 41 patients with juvenile systemic lupus erythematosus (JSLE) and 27 healthy volunteers. Disease activity was determined by SLEDAI score. Peripheral monocytes were stained for CD14, Fas and Bcl-2 molecules, and cellular expressions were determined by flow cytometry. Soluble CD14 levels were measured by a quantitative ELISA kit. JSLE patients, those with active disease and those with nephritis, presented significantly reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes compared with healthy controls. Significant inverse correlations between percentages of CD14+Fas+ cells, SLEDAI score and anti-dsDNA antibodies were observed. JSLE patients had soluble CD14 levels similar to controls, although sCD14 levels positively correlated with ESR, but not with SLEDAI score. JSLE patients with nephritis also presented sCD14 levels similar to controls. In conclusion, the reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes from JSLE patients depict that monocyte apoptotic mechanisms may be important in lupus pathogenesis.

Peptidylarginine deiminase inhibition is immunomodulatory and vasculoprotective in murine lupus

Recent evidence suggests that enhanced neutrophil extracellular trap (NET) formation activates plasmacytoid dendritic cells and serves as a source of autoantigens in SLE. We propose that aberrant NET formation is also linked to organ damage and to the premature vascular disease characteristic of human SLE. Here, we demonstrate enhanced NET formation in the New Zealand mixed 2328 (NZM) model of murine lupus. NZM mice also developed autoantibodies to NETs as well as the ortholog of human cathelicidin/LL37 (CRAMP), a molecule externalized in the NETs. NZM mice were treated with Cl-amidine, an inhibitor of peptidylarginine deiminases (PAD), to block NET formation and were evaluated for lupus-like disease activity, endothelial function, and prothrombotic phenotype. Cl-amidine treatment inhibited NZM NET formation in vivo and significantly altered circulating autoantibody profiles and complement levels while reducing glomerular IgG deposition. Further, Cl-amidine increased the differentiation capacity of bone marrow endothelial progenitor cells, improved endothelium-dependent vasorelaxation, and markedly delayed time to arterial thrombosis induced by photochemical injury. Overall, these findings suggest that PAD inhibition can modulate phenotypes crucial for lupus pathogenesis and disease activity and may represent an important strategy for mitigating cardiovascular risk in lupus patients.

Association of serum interleukin-6 level with active lupus nephritis

Objective To investigate the association of serum interleukin-6 (IL-6) level with active lupus nephritis (LN).Methods 84 patients with LN who had been treated in our hospital during the period of March 2010 to August 2012 were selected.The disease activity was assessed according to the SLEDAI standards.The patients with a score of more than 10 were in the active phase and those with a score of less than 10 were in the stable phase.40 age and sex matched healthy individuals were recruited as control subjects.The patients in the active phase received cyclophosphamide (CTX) and cortical hormone,while those in the stable phase received no immunosuppressive therapy,and the healthy control subjects did not receive any treatment.IL-6 contents were detected by double sandwich ELISA.The changes in IL-6 contents were compared and analyzed among the three groups.Results Before treatment,Serum IL-6 level was significantly higher in patients in the active phase than those in the stable phase and the healthy controls [(285.44 ± 76.56) ng/L vs.(63.23 ± 44.98) ng/L vs.(50.86 ± 40.66) ng/L,P＜0.01].After treatment,serum IL-6 level [(86.53 ± 68.32) ng/L] was significantly declined as compared with the baselines (P＜0.01).The serum IL-6 level did not differ statistically between the patients in the stable and the healthy control subjects (P＞0.05).Conclusions Serum IL-6 level can be used as a sensative marker for the disease activity of lupus nephritis.Detection of serum IL-6 is beneficial and useful for monitoring disease activity and effects of immunosuppressive drugs. Key words: Lupus nephritis; Interleukin-6; Active disease

THU0195 IFNα and its response proteins IP-10 and SIGLEC-1 as biomarkers of disease activity in systemic lupus erythematosus

BackgroundOver the decades, IFNα has been identified as a key cytokine predisposing and driving systemic lupus erythematosus pathology and is thus a frequently studied target molecule. It is assumed that...

SP0055 Microrna in connective tissue disease

MicroRNAs (miRNAs) are endogenous, noncoding, single-stranded RNAs of 19–24 nucleotides in length. They regulate gene expression by messenger RNA degradation and disruption of translation and are important in a wide...

AB0696 Measurement of arterial stiffness in a cross-section of SLE patients and relationship to treatment with intravenous methlyprednisolone – a pilot study

BackgroundSLE is associated with high cardiovascular (CV) morbidity and mortality. Patients have increased exposure to traditional and lupus specific risk factors, which accelerate plaque formation. Recurrent disease flares may facilitate...

AB0197 Endothelial dysfunction in a mouse model of SLE: A role for tumor necrosis factor-α?

BackgroundSystemic lupus erythematosus (SLE) is characterized by a reduced endothelium-dependent relaxation. These alteration have been associated with an early occurrence of traditional cardiovascular risk factors as well as to disease...