Adult-onset Systemic Lupus Erythematosus Research Articles

UnMASking the Diagnosis: Idiopathic Non-Cirrhotic Portal Hypertension Diagnosed in the Setting of Macrophage Activation Syndrome Complicated by Severe Pancreatitis: 2017 Presidential Poster Award

Systemic Lupus Erythematosus (SLE) is a common rheumatologic condition with known GI involvement, most notably autoimmune hepatitis and lupus colitis. Acute pancreatitis (AP) is a rare complication of SLE and is typically associated with disease activity. Macrophage activation syndrome (MAS) is an unusual, hyper-inflammatory response to a rheumatologic stimulus characterized by hyperferritinemia, pancytopenia, thermal dysregulation and multiorgan dysfunction. MAS, more commonly seen in children, has been reported to complicate both adult onset SLE and AP. We present a case of necrotizing AP secondary to an SLE flare ultimately complicated by MAS in an adult patient and successfully treated with Anakinra. A 29 year-old female with SLE and non-adherence to medical therapy was admitted with severe necrotizing AP evidenced by epigastric pain, nausea, oral intolerance, lipase >3000 U/L, and CT scan demonstrating necrosis and inflammation in the pancreatic head. After admission, she developed tachycardia, hypothermia, lactate elevation of 17.2, and hypercarbic respiratory failure with pulmonary edema requiring intubation and mechanical ventilation with aggressive supportive care. Laboratory evaluation demonstrated evidence of DIC with pancytopenia, elevated ANA/ds DNA, and a ferritin of 1332 ng/mL. She was started on methylprednisolone for treatment of a SLE flare with clinical improvement leading to extubation. Following extubation, her ferritin level doubled in association with clinical deterioration raising suspicion for MAS. She was then started on Anakinra resulting in brisk clinical response and down trending ferritin. AP occurs in 1-8% of SLE patients and is proposed to be the result of vascular damage. MAS complicates approximately 5.5% of childhood SLE compared to 0.7% of adult SLE but is more commonly the result of AP in combination with SLE compared to SLE alone and is associated with higher mortality rates. Our case uniquely illustrates a rare etiology of AP and the relationship between systemic diseases and the GI system in a critically ill patient. Treatment of MAS is aimed at treating the underlying SLE; however, our patient required the addition of a chemotherapeutic agent. Anakinra is a novel agent which has been used to treat refractory childhood MAS and was successful in treating this adult patient. To the best of our knowledge, this is the only reported case of refractory MAS due to SLE induced AP necessitating treatment with Anakinra.

Juvenile-onset systemic lupus erythematosus (jSLE) - Pathophysiological concepts and treatment options.

The systemic autoimmune/inflammatory condition systemic lupus erythematosus (SLE) manifests before the age of 16 years in 10-20% of all cases. Clinical courses are more severe, and organ complications are more common in patients with juvenile SLE. Varying gender distribution in different age groups and increasing severity with younger age and the presence of monogenic disease in early childhood indicate distinct differences in the pathophysiology of juvenile versus adult-onset SLE. Regardless of these differences, classification criteria and treatment options are identical.In this article, we discuss age-specific pathomechanisms of juvenile-onset SLE, which are currently available and as future treatment options, and propose reclassification of different forms of SLE along the inflammatory spectrum from autoinflammation to autoimmunity.

Chinese Systemic Lupus Erythematosus Treatment and Research Group Registry IX: Clinical Features and Survival of Childhood-Onset Systemic Lupus Erythematosus in China.

Background:Approximately 15–20% cases of systemic lupus erythematosus (SLE) are diagnosed in children. There have been a few studies reporting the epidemiological data of pediatric-onset SLE (cSLE) in China, neither comparing the differences between cSLE and adult-onset SLE (aSLE). The aim of this study was to describe the impact of age of onset on clinical features and survival in cSLE patients in China based on the Chinese SLE Treatment and Research group (CSTAR) database.Methods:We made a prospective study of 225 cSLE patients (aged < 16 years) and 1759 patients aged 16–50 years based on CSTAR registry. We analyzed initial symptoms, clinical presentations, SLE disease activity, damages, and outcomes of cSLE, as well as compared with aSLE patients.Results:The mean age of cSLE patients was 12.16 ± 2.92 years, with 187 (83.1%) females. Fever (P < 0.001) as well as mucocutaneous (P < 0.001) and renal (P = 0.006) disorders were found to be significantly more frequent in cSLE patients as initial symptoms, while muscle and joint lesions were significantly less common compared to aSLE subjects (P < 0.001). The cSLE patients were found to present more frequently with malar rash (P = 0.001; odds ratio [OR], 0.624; 95% confidence interval [CI], 0.470–0.829) but less frequently with arthritis (P < 0.001; OR, 2.013; 95% CI, 1.512–2.679) and serositis (P = 0.030; OR, 1.629; 95% CI, 1.053–2.520). There was no significant difference in SLE disease activity index scores between cSLE and aSLE groups (P = 0.478). Cox regression indicated that childhood onset was the risk factor for organ damage in lupus patients (hazard ratio 0.335 [0.170–0.658], P = 0.001). The survival curves between the cSLE and aSLE groups had no significant difference as determined by the log-rank test (0.557, P = 0.455).Conclusions:cSLE in China has different clinical features and more inflammation than aSLE patients. Damage may be less in children and there is no difference in 5- year survival between cSLE and aSLE groups.

Alter bei SLE-Diagnose beeinflusst Krankheitsverlauf

Joo YB et al. Differences in Clinical Features and Mortality between Childhood-onset and Adult-onset Systemic Lupus Erythematosus: A Prospective Single-center Study.

Comparison of Disease Characteristics, Organ Damage, and Survival in Patients with Juvenile-onset and Adult-onset Systemic Lupus Erythematosus in a Combined Cohort from 2 Tertiary Centers in Turkey

Age at onset has been shown to affect the clinical course and outcome of systemic lupus erythematosus (SLE). Herein, we aimed to define the differences in clinical characteristics, organ damage, and survival between patients with juvenile-onset (jSLE) and adult-onset SLE (aSLE). For the study, 719 patients (76.9%) with aSLE and 216 (23.1%) with jSLE were examined. Comparisons between the groups were made for demographic characteristics, clinical features, auto-antibody profiles, damage, and survival rates. These results were significantly more frequent in jSLE: photosensitivity, malar rash, oral ulcers, renal involvement, neuropsychiatric (NP) manifestations, and autoimmune hemolytic anemia (AIHA). Of the autoantibodies, a higher frequency of anti-dsDNA and anticardiolipin IgG and IgM were observed in the jSLE group. A significant proportion of patients with aSLE had anti-Sm positivity and pleuritis. The proportion of patients with jSLE who developed organ damage was comparable to that of patients with aSLE (53% vs 47%) and the mean damage scores were similar in both groups. Renal damage was significantly more frequent in jSLE while musculoskeletal and cardiovascular system damage and diabetes mellitus were more prominent in aSLE. Comparison of survival rates of the 2 groups did not reveal any significant differences. We report a higher frequency in the jSLE group of renal involvement, cutaneous symptoms, oral ulcers, NP manifestations, AIHA, and anti-dsDNA positivity. A significant proportion of patients in the jSLE group had damage, most prominently in the renal domain. Our findings might support different genetic/environmental backgrounds for these 2 subgroups.

Childhood versus adult-onset systemic lupus erythematosus: long-term outcome and predictors of mortality.

The aim of this study was to compare survival of childhood-onset systemic lupus erythematosus (c-SLE) and adult-onset SLE (a-SLE) according to initial manifestations. This was a retrospective cohort study. All patients were categorized into c-SLE (≤18years) and a-SLE (>18years). The clinical and serological data at the time of diagnosis were recorded and compared. Kaplan-Meier curves were used to compare survival rates between the two groups. Predictors of mortality were obtained by a backward Cox regression. One hundred eighty patients with c-SLE and 394 patients with a-SLE were enrolled. The female/male ratio was higher in c-SLE (P=0.0001). Lupus nephritis (P=0.002) and valvular heart disease (P=0.025) were more common in c-SLE and a-SLE, respectively. In a 23-year follow-up, 20 patients (11.1%) with c-SLE and 35 patients (8.9%) with a-SLE died. Mortality was not significantly different between them (P=0.4). The main causes of death were nephritis (50% in c-SLE vs. 29% in a-SLE), infections (40% in c-SLE vs. 29% in a-SLE), and circulatory disease (10% in c-SLE vs. 37% in a-SLE). The difference was not significant (P=0.08). Cumulative survival rates after 5, 10, 15, and 20years were 91, 87, 85, and 78% in c-SLE and 93, 90, 90, and 83% in a-SLE, respectively. By multivariate analysis, seizure, proteinuria, and nephritis in c-SLE and seizure, hematuria, and pericarditis in a-SLE had negative prognostic effect on survival. Both c-SLE and a-SLE patients with seizure or renal involvement should be monitored more carefully to prevent ominous outcomes.

Clinical and laboratory manifestations of childhood and adult-onset systemic lupus erythematosus in Cipto Mangunkusumo Hospital

Background Childhood-onset SLE is more severe than the adult type.Objective To compare the clinical and laboratory manifestationsof childhood- and adult-onset systemic lupus erythematosus (SLE).Methods A retrospective study on child and adult SLE patientswas conducted in the Division of Pediatric Allergy and Immunol-ogy, Department of Child Health and Department of Internal Medi-cine, Medical School, University of Indonesia/CiptoMangunkusumoHospital (FKUI/RSCM) Jakarta.Subjects One hundred and twenty-nine subjects met the studycriteria consisting on 54 childhood- onset (41.9%), 75 adult-onset(58.1%), and 122 (94.6%) females and 7 (5.4%) males from Janu-ary 1995 until December 2000.Results Fever, arthralgia and vasculitis were the most frequentsigns found in both childhood-onset and adult-onset SLE. The liver,spleen, lymph nodes, cardiovascular, gastrointestinal tract, andeyes were the organs involved and significantly had a larger pro-portion in the childhood-onset. Decrease of C3 was more frequentlyfound in the childhood-onset. Out of 17 childhood-onset patientswho died, 13 died at the age of 0-11 year-old. Two of the adult-onset patients also died.Conclusion Childhood-onset SLE had some different character-istics compared to adult form

Differences in disease phenotype and severity in SLE across age groups.

ObjectivesSignificant differences have been reported in disease phenotype and severity of systemic lupus erythematosus (SLE) presenting in different age groups. Most indicate a more severe phenotype in juvenile-onset SLE (JSLE). There have been limited studies in older patients and no large studies looking at SLE across all age groups.MethodsWe assessed the effect of age of onset of SLE on the clinical phenotype by analysing data from two large UK cohorts (the UK JSLE Cohort and the UCLH SLE cohort).ResultsA total of 924 individuals were compared (413 JSLE, 511 adult-onset SLE). A female preponderance was present, but less pronounced at either end of the age spectrum. Arthritis was more common with advancing age (93% vs 72%, p < 0.001), whereas renal disease (44% vs 33%, p = 0.001), alopecia (47% vs 23%, p < 0.001) and aphthous ulcerations (39% vs 26%, p = 0.001) were more common in the young. Neuropsychiatric lupus was less common in mature-onset SLE (p < 0.01). JSLE was associated more commonly with thrombocytopenia (21% vs 15%, p = 0.01), haemolytic anaemia (20% vs 3%, p < 0.001), high anti-dsDNA (71% vs 63%, p = 0.009), Sm (22% vs 16%, p = 0.02) and RNP (36% vs 29%, p < 0.04) auto-antibodies. Leucopenia increased with advancing age (p < 0.001). Mortality has been declining over recent decades. However, death rates were substantially higher than the general population. The standardized mortality ratio was 18.3 in JSLE and 3.1 in adult-onset SLE.ConclusionThese data from the largest-ever direct comparison of JSLE with adult-onset SLE suggest an aggressive phenotype of disease with a worse outcome in patients with JSLE and emphasizes the importance of careful follow-up in this population.

Differences in Clinical Features and Mortality between Childhood-onset and Adult-onset Systemic Lupus Erythematosus: A Prospective Single-center Study.

To compare clinical features and mortality between childhood-onset systemic lupus erythematosus (cSLE) and adult-onset SLE (aSLE) in a prospective single-center cohort. A total of 1112 patients with SLE (133 cSLE and 979 aSLE) were enrolled and followed from 1998 to 2012. The 2 groups were compared regarding American College of Rheumatology (ACR) classification criteria for SLE, autoantibodies, disease activity measured by the Adjusted Mean SLE Disease Activity Index (AMS), damage measured by the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI), and medication. The standardized mortality ratio (SMR) was calculated. Predictors of mortality in SLE were evaluated using Cox proportional hazard models. After a mean followup of 7.6 years, patients with cSLE had a higher number of cumulative ACR criteria and a higher AMS (p < 0.001 each), but there was no difference in SDI (p = 0.797). Immunosuppressants were used more frequently by patients with cSLE (p < 0.001). The SMR of cSLE was 18.8 (95% CI 8.6-35.6), significantly higher than that of aSLE (2.9, 95% CI 2.1-3.9). We found cSLE to be an independent predictor of mortality (HR 3.6, p = 0.008). Moreover, presence of hemolytic anemia (7.2, p = 0.034) and antiphospholipid antibody (aPL; 3.8, p = 0.041) increased the magnitude of risk of early mortality more in the patients with cSLE than in those with aSLE. The clinical course of cSLE as measured by number of clinical manifestations and disease activity is worse than that of aSLE. Also, cSLE patients with hemolytic anemia and aPL are at greater risk of death than patients with aSLE who have those features.

Signal transducer and activator of transcription 5 is implicated in disease activity in adult and juvenile onset systemic lupus erythematosus.

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeostasis in humans. It is the principal signaling mechanism for a wide array of cytokines and growth factors. Dysregulated cytokine action on immune cells plays an important role in the initiation and progress of systemic lupus erythematosus (SLE). In this study, we tried to assess the role of STAT5 in systemic lupus erythematosus and correlate its phosphorylation level with the disease activity. The activation of the STAT5 was assessed by measuring the level of expression of phosphorylated STAT5 (pSTAT5) using flow cytometry on the peripheral blood T and B cells in 58 SLE patients (40 adult and 18 juvenile onset) and on 23 healthy age- and sex-matched controls for both groups. Serum prolactin level was also assessed in the patients and control by ELISA. The study revealed that the level of pSTAT5 was higher in adult SLE patients than in healthy control (p = 0.001) and in juvenile-onset SLE patients versus age-matched control (p = 0.031). A positive correlation existed between the pSTAT5 levels and Systemic Lupus Activity Measure (SLAM) score and also with multiple clinical manifestations indicating a potential role of STAT5 signaling in pathogenesis SLE. The pSTAT5 signaling is implicated in the disease activity of SLE and may be a useful target of therapy by correcting the dysregulation of cytokines involved in the disease pathogenesis.

Early Life Factors Associated with Adult-Onset Systemic Lupus Erythematosus in Women.

Exposure early in life can influence adult disease and immunity, but the role of early life exposures in risk of systemic lupus erythematosus (SLE) is not established. Women in a national cohort (ages 35-74) provided data on perinatal, maternal, and sociodemographic factors, longest residence to age 14, and residential farm history of at least 12 months to age 18. Cases (N = 124) reported SLE diagnosed age 16 years or older with use of disease modifying antirheumatic drugs. Non-cases (N = 50,465) did not report lupus. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression adjusting for age and race/ethnicity. SLE was associated with low birthweight (data on 84 cases and 36,477 non-cases; <2,500 versus 3,000 to <3,500 g OR = 2.2; 95%CI 1.2, 3.9) and preterm birth (57 cases and 22,784 non-cases; ≥1 month early versus full-term OR = 3.4; 95%CI 1.6, 7.4). Considering longest childhood residence to age 14, SLE was associated with more frequent pesticide use (e.g., at least monthly OR = 2.3; 95%CI 1.3, 4.1). SLE was associated with having an early and extended childhood farm residence (i.e., prenatal/maternal farm exposure and longest childhood farm residence OR = 1.8; 95%CI 1.1, 3.0 versus neither). In those with a childhood-only farm residence of 12+ months, agricultural pesticide use was associated with SLE, with the strongest associations for direct personal exposures. The association of SLE with preterm birth is consistent with studies in other populations and with an observed association with low birthweight. The associations of SLE with childhood exposure to residential and agricultural pesticides warrant further study.

Pharmacological Management of Childhood-Onset Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a rare, severe, multisystem autoimmune disorder. Childhood-onset SLE (cSLE) follows a more aggressive course with greater associated morbidity and mortality than adult-onset SLE. Its aetiology is yet to be fully elucidated. It is recognised to be the archetypal systemic autoimmune disease, arising from a complex interaction between the innate and adaptive immune systems. Its complexity is reflected by the fact that there has been only one new drug licensed for use in SLE in the last 50years. However, biologic agents that specifically target aspects of the immune system are emerging. Immunosuppression remains the cornerstone of medical management, with glucocorticoids still playing a leading role. Treatment choices are led by disease severity. Immunosuppressants, including azathioprine and methotrexate, are used in mild to moderate manifestations. Mycophenolate mofetil is widely used for lupus nephritis. Cyclophosphamide remains the first-line treatment for patients with severe organ disease. No biologic therapies have yet been approved for cSLE, although they are being used increasingly as part of routine care of patients with severe lupus nephritis or with neurological and/or haematological involvement. Drugs influencing Bcell survival, including belimumab and rituximab, are currently undergoing clinical trials in cSLE. Hydroxychloroquine is indicated for disease manifestations of all severities and can be used as monotherapy in mild disease. However, the management of cSLE is hampered by the lack of a robust evidence base. To date, it has been principally guided by best-practice guidelines, retrospective case series and adapted adult protocols. In this pharmacological review, we provide an overview of current practice for the management of cSLE, together with recent advances in new therapies, including biologic agents.

Demographic Presentation, Activity Indices, Damage Index: Comparative Study Between Pediatric Lupus Erythematosus Versus Adult Systemic Lupus Erythematosus in Sample Egyptian Population

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that can affect all organ systems due to alterations of both the innate and adaptive immune systems. Although onset during infancy is rare, the incidence of SLE rises steadily during childhood until mid-adulthood, especially among females. In this study we aimed to highlight the possible discrepancies in clinical presentations as well as serological profiles of pediatric and adult onset SLE patients, we also focused attention on the disease assessment by SLE activity index (SLE DDI) and damage index at time of presentation. Subjects were subdivided into 2 groups: Group I: A total of 92 Pediatric systemic lupus erythematosus (pSLE) that were selected from the students attending the school children hospital of medical health insurance. Group II: A total of 90 adult systemic lupus erythematosus (aSLE) patients and were recruited from those attending the Alexandria Main University Hospital and outpatient clinic. All patients were subjected to: detailed history taking and complete physical and mental examination, also activity indices as well as damage index were applied for every lupus patient of the studied groups, laboratory investigations were done for all patients. Our results demonstrated that, regarding mucocutaneous manifestations: pSLE patients have values higher than aSLE patients regarding photosensitivity (63.3% and 61.1%) and vascular lesions (23.9% and 22.2%) respectively. Regarding haematological manifestations: pSLE patients have values higher than aSLE patients regarding anemia (86.96% and 84.4), leucopenia (28.3% and 22.22) and thrombocytopenia (46.7% and 25.56%) respectively. Regarding renal abnormalities, pSLE patients have higher incidence of nephritic syndrome than aSLE patients. Regarding SLEDAI, pSLE patients have values statistically higher than aSLE patients. Regarding SLAM, pSLE patients have values statistically higher than aSLE patients, while no differences of damage index was noticed.

The association between initial manifestations of childhood‐onset systemic lupus erythematosus and the survival

Childhood-onset systemic lupus erythematosus (cSLE) comprises 15-20% of patients with SLE. Although several studies have reported the outcomes of adult-onset SLE, few investigations have been conducted on cSLE in the Middle East. In a retrospective study, all children with SLE admitted to our tertiary referral center between 1992 and 2011 were recruited. The clinical and laboratory data at the time of onset were recorded and analyzed. Kaplan-Meier analysis was used to calculate the survival rates. Cox regression analysis was applied to assess the predictors of mortality. One hundred and eighty-eight children diagnosed with SLE were enrolled during the study period. Nine patients were censored due to loss to follow-up (6) and incomplete data (3 cases). Mean age of patients at the time of onset was 14.4 (3.05) years. Only 22 (11.8%) children were younger than 10 years at the time of disease onset. In total, 20 patients (11%) died, all after the first decade of life. The most common cause of death was lupus nephritis (10 patients, 50% of deaths) followed by infections (35%), cerebrovascular accidents (10%) and alveolar hemorrhage (5%). Cumulative survival rate after 5, 10, 15 and 20 years was 91, 87, 85, and 79%, respectively. Having hematuria or pleurisy at the time of SLE onset had a negative effect on survival in multivariate analysis. cSLE survival in Iran was comparable to that in other developing countries. Baseline presentation with hematuria predominantly increased the mortality rate in cSLE. Prospective and larger studies in future may unfold other aspects of cSLE.

Juvenile-Onset versus Adult-Onset Systemic Lupus Erythematosus: Different Clinical and Serological Patterns

Juvenile-Onset versus Adult-Onset Systemic Lupus Erythematosus: Different Clinical and Serological Patterns

Juvenile-onset systemic lupus erythematosus: how to diagnose and manage

Abstract Systemic lupus erythematosus (SLE) is the prototypic autoimmune disorder, characterised by auto-antibody production against nuclear antigens. Juvenile-onset systemic lupus erythematosus (JSLE) is a more severe form than the adult-onset disease, with a more balanced gender ratio. The disorder is of unknown aetiology with hormonal, genetic and environmental factors all thought to play a role. Diagnosis is notoriously difficult due to the protean clinical signs and symptoms. Specialist input is necessary given the severity and range of clinical manifestations during an important time of growth and development. A personalized approach is required to provide optimal care for an individual's needs. A holistic, multi-disciplinary approach to the management of JSLE is crucial. Medical therapy aims at dampening down the immune response. Biological therapies that target specific points in the immune system are becoming available. Clinical trials in JSLE are sparse with much of the management guided by evidence derived from adult-onset SLE. The first trial of biologic use in JSLE is currently underway. Further investigations of aetiology and clinical trials in JSLE are required to inform management and identify targets for future therapy.

Inflammasome polymorphisms in juvenile systemic lupus erythematosus

Inflammasome is the cytoplasmic complex responsible for pro-IL1 β cleavage and secretion of IL-1β. Recently our group reported the first association between polymorphisms in the inflammasome receptor NLRP1 and adult-onset systemic lupus erythematosus (SLE) “di per se” and especially in SLE-associated renal disease, suggesting the involvement of NLRP1-inflammasome in the immune dysregulation characteristic of SLE patients. Considering that juvenile-onset SLE (JSLE) is more severe than adult SLE, and that the genetic background plays a major role in the early development of autoimmune diseases, we analysed selected polymorphisms in inflammasome genes (NLRP1, NLRP3, CARD8, IL1B, TNFAIP3) of children and adolescents with JSLE (n = 90) and in healthy controls (n = 144). A single polymorphism in IL1B, and not NLRP1, gene resulted in association with JSLE, suggesting that IL-1 β is involved in the pathogenesis of SLE, but different genes could play specific role in adult- or early-onset disease.

Comparison of clinical and serological differences among juvenile-, adult-, and late-onset systemic lupus erythematosus in Korean patients

We investigated whether systemic lupus erythematosus (SLE) patients could be distinguished based on the time of disease onset and, if so, whether the groups differed in their clinical and laboratory features in ethnically homogeneous Korean patients. We enrolled 201 SLE patients with available clinical data at the time of onset of SLE from the lupus cohort at Chonnam National University Hospital. Sociodemographic, clinical, and laboratory data, including autoantibodies, and concomitant diseases were found at the time of diagnosis of SLE by reviewing patient charts. We divided SLE patients according to age at SLE diagnosis into three groups: juvenile-onset SLE (JSLE, diagnosed at ≤ 18 years), adult-onset SLE (ASLE, diagnosed at 19-50 years), and late-onset SLE (LSLE, diagnosed at >50 years), and compared baseline demographic, clinical, and relevant laboratory findings. Of the 201 patients, 27 (14.4%), 149 (74.1%), and 25 (12.4%) were JSLE, ASLE, and LSLE patients, respectively. Fever, oral ulcers, nephritis, anemia, and thrombocytopenia were more common in JSLE patients than ASLE or LSLE patients (p < 0.05, < 0.05, 0.001, < 0.05, and < 0.05, respectively). However, Sjögren's syndrome was more frequent in LSLE patients than JSLE or ASLE patients (p < 0.05). Disease activity was significantly higher in JSLE patients than in ASLE or LSLE patients (p < 0.001). Anti-dsDNA and anti-nucleosome antibodies were found more frequently in JSLE patients and less frequently in LSLE patients (p < 0.05 and 0.005, respectively) and decreased complement levels were more common in JSLE patients and less common in LSLE patients (p < 0.001, 0.001, and < 0.05, respectively). Our results indicate that SLE patients present with different clinical and serological manifestations according to age at disease onset. JSLE patients have more severe disease activity and more frequent renal involvement and LSLE patients have milder disease activity, more commonly accompanied by Sjögren's syndrome, at disease onset.

Endothelial progenitor cell phenotype and function are impaired in childhood-onset systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by increased cardiovascular risk in adult-onset and childhood-onset SLE. Type I interferons (IFNs) appear to play a prominent role in premature vascular damage in adult-onset SLE, at least in part, by inducing impairments in the phenotype and function of endothelial progenitor cells (EPCs), thereby hampering vascular repair. It is not clear whether EPC dysfunction is present in childhood-onset SLE in association with a type I IFN signature. The phenotype and numbers of EPCs were quantified in patients with childhood-onset SLE, patients with juvenile idiopathic arthritis (JIA), and matched healthy control subjects. In a separate cohort of patients with childhood-onset SLE, markers of subclinical atherosclerosis and endothelial dysfunction were quantified using standardized protocols and analyzed for associations with serum type I IFN activity. EPC numbers and function were significantly decreased in patients with childhood-onset SLE compared with patients with JIA and healthy control subjects. Serum from patients with childhood-onset SLE impaired differentiation of EPCs into mature endothelial cells in healthy controls, and this effect was blocked by inhibition of the type I IFN pathway. Type I IFN activity in serum was not significantly associated with subclinical atherosclerosis and endothelial function in patients with childhood-onset SLE. As in adult-onset SLE, childhood-onset SLE is characterized by phenotypic and functional EPC abnormalities, which are likely triggered by type I IFNs. Although cross-sectional analysis revealed no global association between type I IFN signatures and vascular measures of subclinical atherosclerosis, longitudinal assessments are needed to evaluate whether progression of vascular damage in patients with childhood-onset SLE is associated with type I IFNs, as observed in patients with adult-onset SLE.

289. Comparison of Disease Characteristics and Organ Damage in Patients with Juvenile and Adult-Onset Systemic Lupus Erythematosus in a Large Cohort from Turkey

289. Comparison of Disease Characteristics and Organ Damage in Patients with Juvenile and Adult-Onset Systemic Lupus Erythematosus in a Large Cohort from Turkey