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Objectives: Remission in systemic lupus erythematosus (SLE) is defined through a combination of 'clinical SLE Disease Activity Index (cSLEDAI)=0', 'physician's global assessment (PGA) <0.5' and 'prednisone (PDN) ≤5 mg/day'. We investigated the performance of these items, alone or in combination, in defining remission and in predicting SLICC/ACR Damage Index.Methods: We tested seven potential definitions of remission in SLE patients followed-up for ≥5 years: PDN ≤5 mg/day; PGA <0.5; cSLEDAI=0; PGA <0.5 plus PDN ≤5 mg/day; cSLEDAI=0 plus PGA <0.5; cSLEDAI=0 plus PDN ≤5 mg/day; cSLEDAI=0 plus PDN ≤5 mg/day plus PGA <0.5. The effect of these definitions on damage was evaluated by Poisson regression analysis; the best performance was identified as the lowest Akaike and Bayesian information criterion (AIC and BIC). Positive and negative predictive values in identifying no damage increase were calculated.Results: We included 646 patients (mean±SD disease duration 9.2±6.9 years). At multivariate analysis, ≥2 consecutive year remission according to all definitions protected against damage (OR, 95% CI: PGA <0.5 0.631, 0.444 to 0.896; cSLEDAI=0 0.531, 0.371 to 0.759; PGA <0.5 plus PDN ≤5 mg/day 0.554, 0.381 to 0.805; cSLEDAI=0 plus PGA <0.5 0.574, 0.400 to 0.826; cSLEDAI=0 plus PDN ≤5 mg/day 0.543, 0.376 to 0.785; cSLEDAI=0 plus PDN ≤5 mg/day plus PGA <0.5 0.532, 0.363 to 0.781, p<0.01 for all), except PDN ≤5 mg/day, which required four consecutive years (OR 0.534, 95% CI 0.325 to 0.877, p=0.013). Positive and negative predictive values were similar; however, cSLEDAI=0 showed the best performance (AIC 1082.90, BIC 1109.72, p<0.0001). Adding PGA <0.5 and/or PDN ≤5 mg/day to cSLEDAI=0 decreased remission duration (-1.8 and -1.5 year/patient, respectively) without increasing cSLEDAI=0 performance in predicting damage accrual.Conclusions: cSLEDAI=0 is the most attainable definition of remission, while displaying the best performance in predicting damage progression in the short-to-mid-term follow-up. [ABSTRACT FROM AUTHOR]

Background and Aim: Systemic lupus erythematosus (SLE) is associated with accelerated atherogenesis. Traditional risk factors do not seem to fully explain this process in patients with SLE and no other imaging/serum biomarkers have so far improved risk stratification. Here, we focused on the role of adiponectin in women with SLE.Methods and Results: This is a sub-analysis of a validated cohort enrolling eighty females (age 18-65 years) affected by SLE. Patient underwent a single blood sampling and carotid echography. Serum adipocytokines (i.e. leptin, resistin and adiponectin) were assessed by enzyme-linked immunosorbent assay (ELISA). Patients with a carotid plaque (n = 23) were older, with longer duration of the disease, chronic use of corticosteroids, and immunosuppressive therapies. As expected, patients with a carotid plaque had increased vascular risk and high serum levels of inflammatory biomarkers, total and LDL cholesterol and adiponectin. Significant positive correlation between serum adiponectin and presence of a carotid plaque was found independently of patient age, SCORE Risk Charts, duration of disease, and SLE treatments.Conclusions: These results indicate that high serum adiponectin is associated with accelerated carotid atherosclerosis in SLE young women and it might be useful to improve vascular risk stratification in this patient setting. [ABSTRACT FROM AUTHOR]

Objectives: To investigate how the different components of sleep dysfunction described in SLE patients combine together in sleep clusters. Methods: We conducted a cross-sectional study on a perspective cohort of 79 SLE patients (mean age 8.2 ± 14.3 years). Sleep was evaluated using Pittsburgh Sleep Quality Index (PSQI). Clusters were defined using the single components of PSQI in a hierarchical clustering model. We used Beck Depression Inventory, Hamilton Anxiety Rating Scale, and Medical Outcomes Study Short Form 36 (SF36) to measure depressive symptoms, anxiety, and quality of life, respectively. Results: Three sleep clusters were identified. The cluster 1 (N = 47) is characterized by the lowest values of PSQI total score. The cluster 2 (N = 21) presents higher values of sleep latency, but sleep duration similar to cluster 1. In cluster 3 (N = 11), we found sleep latency increased as in cluster 2, but the highest values of PSQI total score and reduced sleep duration. Scores of anxiety and sedentary time were higher in clusters 2 and 3 than in cluster 1. Cluster 3 presented the highest scores of depression and reduced mental and physical components of SF36. Conclusions: The combination of different sleep components in SLE patients allowed us to identify three patterns of dysfunction: a first cluster with better sleep latency and duration, a second with increased sleep latency but conserved duration, and a third with impairment of both latency and duration. The stratification of sleep disorders in clusters might be useful for the personalization of therapy in relation to sleep cluster membership. [ABSTRACT FROM AUTHOR]

Prolonged remission (PR), defined as a 5-year consecutive period of no disease activity based on SLEDAI-2K, has been reported to be associated with a lower damage accrual over time in patients with systemic lupus erythematosus (SLE), as the consequence of a lower activity burden. Since disease activity is considered to play a role in the incidence of cardiovascular disease (CVD), we investigated the relationship, if any, between PR and the occurrence of a subsequent first CV event in patients with SLE. Out of 488 patients consecutively admitted to two tertiary Italian centers from November 1, 2000, to December 31, 2016, the 294 patients, who had been followed at least for 5 years, had not experienced any CV event at admission, and had been visited biannually during follow-up, were considered for the present study. The incidence of a first CV in patients who had achieved PR was compared with that registered in those who had not. Moreover, it was compared among PR patients subdivided into three groups: complete remission, clinical off-corticosteroids (offCR), and clinical on-corticosteroids remission (onCR). Kaplan-Meier curves and the log-rank test were used to analyze differences in event-free survival among groups. Cox regression was used to investigate disease and therapeutic features associated with the development of a first CV event. During 9 years median follow-up time, 24 (8.1%) CV events occurred. Out of the 294 patients, 126 (42.8%) had achieved PR. Kaplan-Meier analysis revealed a greater overall CV event-free rate in these patients as compared to both those with a shorter lasting remission and those who had never remitted (log-rank test χ2 = 14.43; p = 0.0001). In addition, CV outcome did not differ among PR patients, irrespectively the type of remission achieved (p > 0.05). At multivariate analysis, hydroxychloroquine therapy and PR resulted to be protective (HR 0.19; HR 0.18), while arterial hypertension and antiphospholipid positivity increased the risk of a first CV event (HR 2.61; HR 2.47). The PR, whichever the subtype, is associated with a better CV outcome and should be considered as a treat-to-target goal in the CV risk management of the lupus patient. [ABSTRACT FROM AUTHOR]

Abstract Autoimmune rheumatic diseases are characterised by an abnormal immune system response, complement activation, cytokines dysregulation and inflammation. In last years, despite many progresses in managing these patients, it has been shown that clinical remission is reached in less than 50% of patients and a personalised and tailored therapeutic approach is still lacking resulting in a significant gap between guidelines and real-world practice. In this context, the need for biomarkers facilitating early diagnosis and profiling those individuals at the highest risk for a poor outcome has become of crucial interest. A biomarker generally refers to a measured characteristic which may be used as an indicator of some biological state or condition. Three different types of medical biomarkers has been suggested: i. mechanistic markers; ii. clinical disease markers; iii. therapeutic markers. A combination of biomarkers from these different groups could be used for an ideal more accurate diagnosis and treatment. However, although a growing body of evidence is focused on improving biomarkers, a significant amount of this information is not integrated on standard clinical care. The overarching aim of this work was to clarify the meaning of specific biomarkers during autoimmune diseases; their possible role in confirming diagnosis, predicting outcome and suggesting specific treatments. [ABSTRACT FROM AUTHOR]

Objective: Systemic lupus erythematosus (SLE) is an autoimmune systemic disease and its pathogenesis has not yet been completely clarified. Patients with SLE show a deranged lipid metabolism, which can contribute to the immunopathogenesis of the disease and to the accelerated atherosclerosis. Resolvin D1 (RvD1), a product of the metabolism of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA), acts as a specialized proresolving mediator which can contribute in restoring the homeostasis in inflamed tissues. The aim of the present pilot study is to evaluate plasma levels of RvD1 in patients with SLE and healthy subjects, investigating its potential role as a biomarker of SLE and assessing its relationship with disease activity and laboratory parameters.Methods: Thirty patients with SLE and thirty age- and sex-matched healthy subjects (HSs) have been consecutively recruited at Campus Bio-Medico University Hospital. RvD1 plasma levels were measured by ELISA according to the manufacturer's protocol (Cayman Chemical Co.). RvD1 levels were compared using Mann-Whitney test. Discriminatory ability for SLE has been evaluated by the area under the ROC curve.Results: Lower levels of RvD1, 45.6 (35.5-57.4) pg/ml, in patients with SLE have been found compared to HSs, 65.1 (39.43-87.95) pg/ml (p = 0.0043). The area under the ROC curve (AUC) for RvD1 was 0.71 (95% CI: 0.578-0.82) and the threshold value of RvD1 for the classification of SLE was <58.4 pg/ml, sensitivity 80% (95% CI: 61.4-92.3), and specificity 63.3% (95% CI: 43.9-80.1), likelihood ratio 2.2 (95% CI: 1.3-3.6).Conclusions: The present preliminary study allows hypothesizing a dysregulation of RvD1 in patients with SLE, confirming the emerging role of bioactive lipids in this disease. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to evaluate the proportion of patients with Systemic Lupus Erythematosus (SLE) who did not met the WHO recommendations for physical activity and to evaluate the amount of time spent in sedentary behavior. Methods: SLE patients were consecutively enrolled in a cross sectional study. The type and the time spent in physical activity and sedentary behavior were evaluated using the IPAQ short form questionnaire. The adequate physical activity was defined according to the 2010 WHO recommendations for health and the sedentary behavior according to the 2017 SBRN consensus. We also assessed quality of life using SF-36, mood disorders using BDI and HAM-H, fatigue using Facit-Fatigue and sleep disorders using PSQI scores. Results: Physical activity was not sufficient to meet WHO recommendations in 56 of 93 SLE patients (60%). SLE patients spent a median (95% range) of 180 (0–600) minutes everyday in sedentary activities. The length of daily sedentary time was more than 6 hours in 25% of SLE patients. In multivariable analysis, the factors associated to the probability of not meeting WHO criteria was only the time of exposure to antimalarials (OR 0.88, p 0.03) and the factors related to the probability of being in the upper tertile of sedentary time (more than 270 minutes) were age (OR 1.04, p 0.02), disease activity expressed by SELENA-SLEDAI score (OR 1.2, p 0.01) and Facit-fatigue score (OR 0.94, p 0.04). Conclusion: A relevant proportion of SLE patients were inadequately physically active. It is essential to improve the awareness of the importance of increase physical activity and reduce sedentary time. A better control of disease activity and fatigue and a prolonged use of antimalarials could help to reach this notable goal. [ABSTRACT FROM AUTHOR]

Introduction: Systemic Lupus Erythematosus (SLE) is associated to an increased prevalence of Metabolic Syndrome (MeS) and to a reduction of Quality of Life (QoL). The aim of this study is to evaluate the association between MeS and QoL in SLE. Methods: SLE patients were consecutively enrolled in a cross sectional study. MeS was defined according to IFD definition. Therapy with glucocorticoids (GC) and antimalarial was analyzed as cumulative years of exposure. We used a cut off of 7.5 mg of prednisone to define high daily dose of GC. QoL was quantified using SF-36. We used BDI and HAM-H to assess symptoms of mood disorders. Fatigue was evaluated using Facit-Fatigue, physical activity using IPAQ, sleep quality using PSQI and alexithymia using TAS-20. Results: We enrolled 100 SLE patients. MeS prevalence was 34%. Patients with MeS presented reduced scores in SF-36 MCS and PCS compared to patients without MeS (p 0.03 and p 0.004). BDI and HAM-H score were significantly higher in patients meeting MeS criteria compared to subjects without MeS (p 0.004, p 0.02). These results were confirmed after adjustment for confounders. Compared to patients without MeS, those with MeS presented higher age, lower education level, higher recent SELENA-SLEDAI, higher number of flares, increased SDI, longer cumulative exposure to high dose GC and shorter duration of antimalarial therapy. In the multiple logistic regression model, the variable associated to the Odds Ratio of having MeS were: the average of recent SELENA-SLEDAI (OR 1.15 p 0.04), the years of exposure to high dose of GC (OR 1.18 p 0.004), the years of exposure to antimalarials (OR 0.82 p 0.03) and the BDI score (OR 1.1 p 0.005). Conclusion: A modern management of SLE should not miss to take all the possible measures to ensure an adequate QoL to SLE patients, with particular attention to those affected by MeS. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are a complex set of diseases characterized by immune system activation and, although many progresses have been done in the last 15 years, several unmet needs in the management of these patients may be still identified. Recently, a panel of international Experts, divided in different working groups according to their clinical and scientific expertise, were asked to identify, debate and formulate a list of key unmet needs within the field of rheumatology, serving as a roadmap for research as well as support for clinicians. After a systematic review of the literature, the results and the discussions from each working group were summarised in different statements. Due to the differences among the diseases and their heterogeneity, a large number of statements was produced and voted by the Experts to reach a consensus in a plenary session. At all the steps of this process, including the initial discussions by the steering committee, the identification of the unmet needs, the expansion of the working group and finally the development of statements, a large agreement was attained. This work confirmed that several unmet needs may be identified and despite the development of new therapeutic strategies as well as a better understanding of the effects of existing therapies, many open questions still remain in this field, suggesting a research agenda for the future and specific clinical suggestions which may allow physicians to better manage those clinical conditions still lacking of scientific clarity. [ABSTRACT FROM AUTHOR]

Introduction. The objective of the present study was to compare QUANTA Flash dsDNA, a chemiluminescent immunoassay (CIA) on the BIO-FLASH, a rapid-response chemiluminescent analyzer, to three other anti-dsDNA antibody assays and to Crithidia luciliae indirect immunofluorescence test (CLIFT). Methods. In the first part of the study, 161 samples, 61 from patients suffering from systemic lupus erythematosus (SLE) and 100 from a disease control group, were tested by QUANTA Flash dsDNA CIA, QUANTA Lite dsDNA SC ELISA, BioPlex 2200 multiplex flow immunoassay (MFI), ImmuLisa dsDNA ELISA, and NOVA Lite CLIFT. A second cohort of 69 SLE patients was then tested by QUANTA Flash dsDNA and CLIFT to expand the study. Results. The overall qualitative agreements varied between 77.0% (NOVA Lite CLIFT versus QUANTA Lite) and 89.4% (ImmuLisa versus NOVA Lite CLIFT). The clinical sensitivities for the anti-dsDNA antibody tests varied from 8.2% (NOVA Lite CLIFT) to 54.1% (QUANTA Lite), while the clinical specificities varied from 88.0% (BioPlex 2200) to 100.0% (NOVA Lite CLIFT). Good correlation was found between QUANTA Flash dsDNA and NOVA Lite CLIFT. Conclusion. Significant variations among dsDNA methods were observed. QUANTA Flash dsDNA provides a good combination of sensitivity and specificity for the diagnosis of SLE and good agreement to CLIFT. [ABSTRACT FROM AUTHOR]

Autoantibodies to double-stranded DNA (dsDNA) are, by definition, serological markers of systemic lupus erythematosus. However, the clinical value of anti-dsDNA antibodies largely depends on the assay principle and analytical variables of the methods used to quantitate and immunologically characterize them. In the present article, an overview of current methods for anti-dsDNA antibody detection is presented, together with a look at the future trends in technologies newly employed in this field. [ABSTRACT FROM AUTHOR]

Lactoferrin (LF) is a multifunctional iron-binding protein present in several mucosal secretions as well as in secondary granules of polymorphonuclear leukocytes (PMN). Anti-LF antibodies, which belong to antineutrophil cytoplasmic antibodies (ANCA), have been described in several immunomediated diseases, including systemic lupus erythematosus (SLE), with conflicting results regarding either their prevalence or clinical associations. We studied the prevalence and isotype distribution of anti-LF and their association with clinical manifestations, disease activity, and other autoantibodies in 97 patients (83 women) affected by SLE. Anti-LF were detected by enzyme-linked immunosorbent assay. Disease activity was assessed using the Systemic Lupus Activity Measure (SLAM). Cutoff for antibody positivity was set at three standard deviations (SD) above the mean optical density obtained in sera from 34 healthy subjects. Positive sera were arbitrarily subdivided into low (from >3 to 5 SD), medium (from >5 to 10 SD), and high (>10 SD) positive. IgG, IgM, and IgA anti-LF were detected in 53, 18, and 14 patients, respectively. IgG1, IgG2, IgG3, and IgG4 anti-LF were demonstrated in 34, 10, 31, and 35 patients, respectively. IgG anti-LF at the medium/high level were found in 33 patients, correlated with disease activity ( p=0.017), anti-dsDNA (0.04), and anticardiolipin antibodies ( p=0.02) and were associated with Raynaud’s phenomenon ( p=0.028), renal involvement ( p=0.007), serositis ( p=0.026), and history of thrombosis ( p=0.006). Anti-LF of IgM, IgA, or IgG subclass isotypes showed no correlation with clinical and serological findings. Our results demonstrate that anti-LF are frequently present in patients affected by SLE. IgG anti-LF at the medium/high level are associated with some clinical manifestations and other autoantibodies. However, it remains to be established whether anti-LF play a specific pathogenic role. [ABSTRACT FROM AUTHOR]

Purpose: To review the potential pathogenic mechanisms of transient visual symptoms (TVS) in the course of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), to discuss the most common clinical features associated with the occurrence of TVS, and to explore possible treatment options for these patients.Methods: The literature regarding the clinical and laboratory characteristics of SLE and APS patients experiencing TVS is reviewed from 1979 onward. A brief review of the wide spectrum of ophthalmologic features occurring in SLE and APS is also provided.Results: Data emerging from the review process point to thromboembolism as the most probable cause of TVS in SLE and APS. Thromboembolisms are likely induced by cardiac valve abnormalities and should be treated with anticoagulant drugs.Conclusion: While progress has been made in understanding the association of TVS with SLE and APS, further investigation is needed to clarify this interesting relationship. [ABSTRACT FROM AUTHOR]

Abstract: In systemic lupus erythematosus (SLE), the risk of development of cardiovascular disease is dramatically increased. Inflammatory and immune-mediated mechanisms, favouring early alterations of the arterial wall are strongly involved in promoting the development of atherosclerosis (ATS) in young SLE patients. In SLE, sonographic measurements of carotid intima-media thickness are able to recognize clinical, but not always subclinical, ATS. On the contrary, assessment of endothelial function and vascular stiffness through sonography-based techniques may be useful to reveal or exclude subclinical ATS. More efforts should be done to find a comprehensive approach to the study of subclinical ATS in SLE patients, since an early diagnosis may have a significant value in preventing the development of major vascular diseases. [ABSTRACT FROM AUTHOR]

Background: Ultrasound evaluation of carotid intima‐media thickness (cIMT) has been extensively used for potentially improving cardiovascular (CV) risk stratification in several patients' categories. Subjects with systemic lupus erythematosus (SLE) have been investigated by both imaging and molecular biomarker approaches with contrasting results. Here, we focused on the role of osteopontin (OPN) as biomarker of subclinical atherosclerosis associated with SLE. Materials and Methods: Eighty females (age 18‐65 years) affected by SLE and eighty age‐matched healthy female controls without a clinical history of CV disease underwent ultrasound evaluation of cIMT and blood sample assay of high‐sensitivity C‐reactive protein (hs‐CRP) and OPN. Results: Healthy controls and SLE patients significantly differed for CV risk factors (ie, waist circumference, hypertension and dyslipidaemia) and the inflammatory status. Noteworthy, an opposite association between cIMT and OPN was observed in the two study groups. Whereas OPN was positively associated with mean cIMT (r = 0.364; P = 0.001) in SLE patients, a negative correlation was found in healthy controls. Furthermore, in SLE patients increased circulating levels of OPN were associated with the use of hydroxychloroquine and the positivity for the anti‐dsDNA autoantibodies. At linear regression analysis, only OPN remained independently associated with cIMT also after adjustment for age, smoking pack‐year, Heart SCORE, disease length and steroid therapy length. Conclusions: These results indicate that serum OPN levels were strongly associated with subclinical atherosclerosis in patients with LES and it might be a useful CV biomarker that requires additional validation in larger trials. [ABSTRACT FROM AUTHOR]

The endocannabinoid (eCB) system plays a key role in many physiological and pathological conditions and its dysregulation has been described in several rheumatological and autoimmune diseases. Yet, its possible alteration in systemic lupus erythematosus (SLE) has never been investigated. Here, we aimed filling this gap in plasma and peripheral blood mononuclear cells (PBMCs) of patients with SLE and age- and sex- matched healthy subjects (HS). Liquid chromatography-mass spectrometry quantitation of eCB levels highlighted that plasma levels of 2-arachidonoylglycerol (2-AG) were significantly increased in SLE patients compared to HS (p = 0.0059), and among SLE patients, highest 2-AG levels were associated with a lower disease activity. No differences were found in N- arachidonoylethanolamine (AEA) and its congeners N -palmitoylethanolamine (PEA) and N -oleoylethanolamine (OEA) concentrations between the two groups. Moreover, gene expression analysis of metabolic enzymes and receptor targets of eCBs and investigation of functional activity and protein expression of selected components of eCB system disclosed a deranged 2-AG metabolism in patients with SLE. Indeed, expression and functional activity of 2-AG biosynthetic enzyme DAGL were selectively enhanced in PBMCs of SLE patients compared to HS. In conclusion, our results demonstrate, for the first time, an alteration of eCB system in SLE patients. They represents the first step toward the understanding of the role of eCB system in SLE that likely suggest DAGL and 2-AG as potential biomarkers of SLE in easily accessible blood samples. Our data provides proof-of-concept to the development of cannabis-based medicine as immune-modulating agents. [ABSTRACT FROM AUTHOR]

Abstract: Neurological involvement is considered to be a serious complication of systemic lupus erythematosus (SLE). Neuroimaging plays an important role in detecting neurological abnormalities in SLE patients. Conventional magnetic resonance imaging (cMRI) is generally the most valid neuroimaging technique for detecting alterations in the central and peripheral nervous systems. However it may occasionally fail in neuropsychiatric SLE (NPSLE). This is especially the case when the image is not very clear and may depend on the wide variety of neurological and psychiatric manifestations that define this disease. During the last twenty years, this has led to the testing of other radiological instruments, such as single photon emission computed tomography (SPECT), which is complementary to cMRI and seems to furnish additional information, and colour Doppler sonography, which provides minimal additional benefits. Our paper aims to provide a general overview of NPSLE, focusing particularly on the strengths and weaknesses of modern neuroimaging. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the role of vascular endothelial growth factor (VEGF) in accelerated atherosclerosis in patients with Systemic Lupus Erythematosus (SLE). Methods: We have enrolled 80 SLE female patients and 80 age-matched healthy control females who underwent a structured interview, physical examination, routine laboratory tests, VEGF plasma level determination and B-mode ultrasonography of carotid arteries to determine carotid intima media thickness (IMT). Framingham risk factors for cardiovascular events were also calculated and VEGF plasma levels were correlated with traditional and nontraditional cardiovascular risk factors. Results: SLE was significantly associated with higher mean IMT values (0.74±0.15 mm versus 0.59±0.12 mm in controls, p <0.001) and higher mean plasma VEGF levels (307.9±292.2 pg/mL versus 120.7±118.4 pg/mL in controls, p <0.001) independently from age, smoking habits, and Framingham risk factors. A significant correlation was also found between IMT and VEGF values (r =0.25; p <0.001). Conclusion: We show that SLE patients have increased mean IMT and VEGF values as compared with healthy age-matched controls and that IMT and VEGF values are independently and directly associated with SLE disease. [Copyright &y& Elsevier]