aSLE Patients Research Articles

Sera from patients with active systemic lupus erythematosus patients enhance the toll-like receptor 4 response in monocyte subsets.

BackgroundSystemic Lupus Erythematosus (SLE) is an auto-immune disease whose complex pathogenesis remains unraveled. Here we aim to explore the inflammatory ability of SLE patients’ sera upon peripheral blood (PB) monocyte subsets and myeloid dendritic cells (mDCs) obtained from healthy donors.MethodsIn this study we included 11 SLE patients with active disease (ASLE), 11 with inactive disease (ISLE) and 10 healthy controls (HC). PB from healthy donors was stimulated with patients’ sera, toll-like receptor (TLR) 4 ligand – lipopolysaccharide or both. The intracellular production of TNF-α was evaluated in classical, non-classical monocytes and mDCs, using flow cytometry. TNF-α mRNA expression was assessed in all these purified cells, after sera treatment.ResultsWe found that sera of SLE patients did not change spontaneous TNF-α production by monocytes or dendritic cells. However, upon stimulation of TLR4, the presence of sera from ASLE patients, but not ISLE, significantly increased the intracellular expression of TNF-α in classical and non-classical monocytes. This ability was related to titers anti-double stranded DNA antibodies in the serum. High levels of anti-TNF-α in the patients’ sera were associated with increased TNF-α expression by co-cultured mDCs. No relationship was found with the levels of a wide variety of other pro-inflammatory cytokines. A slight increase of TNF-α mRNA expression was observed in these purified cells when they were cultured only in the presence of SLE serum.ConclusionsOur data suggest that SLE sera induce an abnormal in vitro TLR4 response in classical and non-classical monocytes, reflected by a higher TNF-α intracellular expression. These effects may be operative in the pathogenesis of SLE.

FRI0417 Comparison of Clinical and Serological Manifestations among Juvenile-, Adult-, and Late-Onset Systemic Lupus Erythematosus Patients in Korea

BackgroundUp to 30-40% of patients with systemic lupus erythematosus (SLE) experience their onset prior to adulthood or at over 50 years of age. Patients with juvenile-onset SLE (JSLE) frequently present...

PReS-FINAL-2355: Comparison of pediatric and adult SLE genetic load

Systemic Lupus Erythematosus (SLE) is a chronic, multisystem autoimmune disease that is the result of the interaction between genetic and environmental factors. Specific genes have been found to be related to the development of SLE and also single nucleotide polymorphisms (SNPs) have been associated to this condition. Although patients with pediatric-onset SLE (pSLE) and adult-onset SLE (aSLE) differ in disease presentation, activity, and outcomes, all studies to date have not found any specific or unique set of genes in pSLE compared to aSLE. Moreover, it has been shown that the frequency of genes in these two SLE populations is the same. However, is possible that an increased genetic load may explain the earlier onset and more severe disease seen in pSLE as compared to aSLE patients.

SAT0210 Comparisons of bone microarchitecture and mechanical properties between childhood- and adult-onset patients with systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) patients are prone to osteoporosis and fracture due to disease itself and its therapies. Many studies of bone quality have involved in patients with adult-onset SLE...

THU0193 Comparative evaluation of cumulative damage in adult and childhood onset systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is a chronic, multisystemic disease affecting predominantly woman in reproductive age. Previous studies have reported childhood-onset (c)SLE to be more severe than adult-onset (a)SLE.ObjectivesThe aim of...

Th17 peripheral cells are increased in diffuse cutaneous systemic sclerosis compared with limited illness: a cross-sectional study

Systemic Sclerosis (SSc) is an autoimmune disease characterized by fibrosis and vasculopathy. A key feature is the presence of T cells in inflammatory lesions. To establish the differences in peripheral blood T helper (Th) subpopulations in diffuse cutaneous (dc) and limited cutaneous (lc) SSc patients, blood samples from 57 dcSSc and 78 lcSSc patients were obtained. Controls were collected from healthy volunteers (n = 16), active systemic lupus erythematosus (aSLE) patients (n = 13), and active rheumatoid arthritis (aRA) patients (n = 12). Mononuclear cells were analyzed by flow cytometry to determine Th1 (CD4+/IFN-γ+), Th2 (CD4+/IL-4+), Th17 (CD4+/IL-17+), and regulatory T cells (Tregs; CD4+/CD25+/Foxp3+) subsets. Th17 and Th1 subsets were increased in SSc groups versus healthy controls (P < 0.001) and aSLE patients (P < 0.001 for Th17 and P < 0.008 for Th1). Th2 cells were higher in dcSSc patients than in the healthy and aSLE groups (P = 0.03 and P = 0.009, respectively). Tregs were increased in the aRA group when compared with SSc patients and healthy controls (P ≤ 0.003). Patients with immunosuppressive treatment had lower numbers of Th17 and Th2 cells (P = 0.02). Our results shed further light into the preponderant role of Th17 and Th1 in patients with SSc. However, these findings certainly deserve to be studied in depth.

Indoleamine 2,3-dioxygenase-expressing peripheral cells in rheumatoid arthritis and systemic lupus erythematosus: a cross-sectional study

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme which suppresses T lymphocyte activity and induces Foxp3+ CD4+ regulatory T cells (Tregs) polarisation. The aim of this study was to evaluate the expression of IDO in freshly isolated peripheral cells as well as to enumerate Tregs and Th17 subpopulation in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. The percentage of IDO-expressing cells as well as Tregs and Th17 was evaluated in 14 active RA- (aRA), 13 inactive RA- (iRA), 7 aSLE-, 12 iSLE-treated patients and 11 healthy donors (controls). Intracellular IDO was analysed by flow cytometry in CD14+, CD8α+, CD16+ and CD123+ cell subpopulations. Tregs and Th17 were assessed by intracellular of Foxp3 and IL17A detection in CD4+ CD14- cells. A total of 50,000 events were recorded for each sample. The amounts of CD14+/CD16-/IDO+, CD14-/CD16+/IDO+ and CD14+/CD16+/IDO+-expressing peripheral cells were slightly lower in inactive vs. active disease in RA and SLE patients. Notwithstanding, only inactive patients had statistically significant lower percentages when compared to controls. aRA and iRA showed a statistically significant decrease in CD8α+/CD123+/IDO+ vs. controls. Meanwhile, only iSLE patients had lower CD8α+/CD123+/IDO+ cells vs. aSLE patients and controls. Th17 subset was present in higher amounts in aRA and iRA patients vs. controls. Tregs showed an increase in aRA patients vs. controls. A decreased percentage of IDO-expressing peripheral cells were determined in iRA and iSLE compared to controls. It could play a critical role in tolerance loss in these diseases.

Acute pancreatitis in pediatric and adult-onset systemic lupus erythematosus: A comparison and review of the literature

This study aimed to compare differences of acute pancreatitis between adult- and pediatric-onset systemic lupus erythematosus (SLE) patients and to clarify the risk factors for mortality. Medical records that carried the dual diagnosis of SLE and acute pancreatitis between 1991 and 2005 were reviewed. Forty-eight episodes of acute pancreatitis were identified in 13 pediatric-onset SLE (pSLE) and 27 adult-onset SLE (aSLE) patients. The prevalence was 1.34% overall, with higher prevalence in pSLE (5.22%) compared with aSLE (0.99%) (p < 0.001). The SLEDAI score on presentation of acute pancreatitis was higher in pSLE (mean ± SD: 21.77 ± 13.09) than in aSLE patients (13.37 ± 8.32) (p = 0.05). Eleven patients died during episodes of acute pancreatitis and mortality rate was significantly higher in pSLE than in the aSLE group (53.8% and 14.8%, respectively, p = 0.015). Mortality was associated with concurrent SLE symptoms (p = 0.049), higher SLEDAI score at presentation of acute pancreatitis (p = 0.011), severe acute pancreatitis (p < 0.001), and the presence of complications (p < 0.001). The multivariate logistic regression analysis showed that severity of acute pancreatitis was the most powerful risk factor for mortality in SLE patients with this disease. In summary, our results indicate that acute pancreatitis occurs more frequently, tends to be more severe, and is associated with higher mortality in pSLE patients when compared with aSLE patient.

Differential association of juvenile and adult systemic lupus erythematosus with genetic variants of oestrogen receptors alpha and beta

Oestrogens acting via nuclear receptors (encoded by ESR1 or ESR2) are important for pathogenesis of systemic lupus erythematosus (SLE). rs2234693 and rs4986938 are two single nucleotide polymorphisms (SNPs) whose C and A variants increase transcription of ESR1 and ESR2, respectively. The T allele of rs2234693 was associated with early onset SLE, whereas the role of rs4986938 in SLE was not reported. Our aim was to examine the role of rs2234693 and rs4986938 in conferring susceptibility to juvenile and adult SLE (jSLE and aSLE). Genotype distribution of both SNPs was analysed in 84 jSLE, 112 aSLE patients and 1001 controls. Allele C of rs2234693 was associated with jSLE (OR = 1.87, p = 0.006, p(corrected) = 0.02), whereas allele A of rs4986938 showed an association with aSLE (OR = 1.46, p = 0.008, p(corrected) = 0.03). In jSLE, rs2234693 C had lower frequency in patients with central nervous system involvement (OR = 0.39, p = 0.005, p(corrected) = 0.04) and showed a trend for increase among males, patients with renal involvement and those without DR2/3 (p < 0.05, p(corrected) > 0.05). Whereas our results are consistent with a role of ESR1 variation in jSLE, more studies are needed since the direction of association was the opposite of that reported previously. The association between rs4986938 (ESR2) and aSLE is a novel finding, consistent with our recent report associating this variant with Graves' disease.

Systemic lupus erythematosus exhibits a dynamic and continuum spectrum of effector/regulatory T cells

Objective: The identification of regulatory T cells (Treg cells) as CD4+CD25high cells may be upset by the increased frequency of activated effector T cells (Teff cells) in inflammatory diseases such as systemic lupus erythematosus (SLE). This study aimed to evaluate the frequency of T-cell subsets according to the expression of CD25 and CD127 in active (A-SLE) and inactive SLE (I-SLE).Methods: Peripheral blood mononuclear cells (PBMCs) from 26 A-SLE patients (SLE Disease Activity Index (SLEDAI) = 10.17 ± 3.7), 31 I-SLE patients (SLEDAI = 0), and 26 healthy controls (HC) were analysed by multicolour flow cytometry.Results: CD25high cell frequency was increased in A-SLE (5.2 ± 5.7%) compared to I-SLE (3.4 ± 3.4%) and HC (1.73 ± 0.8%) (p < 0.01). However, the percentage of FoxP3+ cells in the CD25high subset was decreased in A-SLE (24.6 ± 16.4%) compared to I-SLE (33.7 ± 16) and HC (45 ± 25.1%) (p < 0.01). This was partly due to the increased frequency of Teff cells (CD25highCD127+FoxP3Ø) in A-SLE (10.7 ± 7.3%) compared to I-SLE (8.5 ± 6.5) and HC (6.1 ± 1.8%) (p = 0.02). Hence the frequency of Treg cells (CD25+/highCD127low/ØFoxP3+) was equivalent in A-SLE (1.4 ± 0.8%), I-SLE (1.37 ± 1.0%), and HC (1.13 ± 0.59%) (p = 0.42). A-SLE presented an increased frequency of CD25+CD127+FoxP3+ and CD25ØFoxP3+CD127low/Ø T cells, which may represent intermediate phenotypes between Treg and Teff cells.Conclusions: The present study has provided data supporting normal Treg cell frequency in A-SLE and I-SLE as well as increased frequency of Teff cells in A-SLE. This scenario reflects a Treg/Teff ratio imbalance that may favour the inflammatory phenotype of the disease. In addition, the increased frequency of T cells with putative intermediate phenotypes may be compatible with a highly dynamic immune system in SLE.

Adolescent onset of lupus results in more aggressive disease and worse outcomes: results of a nested matched case–control study within LUMINA, a multiethnic US cohort (LUMINA LVII)

The objective of this study is to examine the clinical features and outcomes of patients with systemic lupus erythematosus (SLE) whose disease began in adolescence [juvenile-onset SLE (jSLE)] compared with adult-onset patients [adult-onset SLE (aSLE)] from a large multiethnic cohort. Systemic lupus erythematosus patients of African-American, Caucasian, or Hispanic ethnicity and >or=1 year follow-up were studied in two groups: jSLE (diagnosed at <or=18 years); aSLE (diagnosed at 19-50 years; matched for gender and disease duration at enrolment). Sociodemographic data, SLE manifestations, disease activity, damage accrual, SLE-related hospitalizations or emergency room visits, drug utilization, mortality and psychosocial characteristics and quality of life were compared. Data were analysed by univariable and multivariable analyses. Seventy-nine patients were studied (31 jSLE, 48 aSLE); 90% were women. Mean (SD) total disease duration was 6.8 (2.7) years in jSLE and 5.6 (3.3) years in aSLE (p = 0.077). Mean age at cohort entry was 18.4 (1.8) and 33.9 (9.2) years in jSLE and aSLE respectively. By univariable analysis, jSLE patients were more commonly of African-American descent, were more likely to have renal and neurological involvements, and to accrue renal damage; jSLE patients had lower levels of helplessness and scored higher in the physical component measure of the SF-36 than aSLE patients. Renal involvement [OR = 1.549, 95% CI (1.397-15.856)] and neurological involvement [OR = 1.642, 95% CI (1.689-15.786)] were independently associated with jSLE by multivariable analysis. There was a larger proportion of African-Americans within the jSLE group. After adjusting for ethnicity and follow-up time, jSLE patients experienced more renal and neurological manifestations, with more renal damage. There was a two-fold higher mortality rate in the jSLE group.