State In Systemic Lupus Erythematosus Research Articles

Frequency and predictors for early-achieved lupus low disease activity state in systemic lupus erythematosus patients treated with telitacicept or belimumab: A real-life, single-center observational study.

To collect real-world data regarding the attainment of the early-achieved lupus low disease activity state (LLDAS) in systemic lupus erythematosus (SLE) patients receiving telitacicept or belimumab treatment, and identify factors predictive of target achievement. Eighty-seven SLE patients who received telitacicept (N=42) or belimumab (N=45) were retrospectively reviewed in this observational study. Clinical and laboratory data, disease activity assessment, and glucocorticoid dosage were collected for analysis. Achieving LLDAS at least once within 24 weeks post-treatment was considered as early-achieved LLDAS. Multivariate regression was used to assess baseline predictive variables for early-achieved LLDAS. Subgroup analysis and interaction tests were also performed to examine the robustness of the results across different sets of baseline characteristics. Prognostic stratification for early-achieved LLDAS was established based on the identified risk factors. During the 24-week follow-up period, LLDAS was achieved by at least one time in 49.43% (43/87) of the patients, with sustained achievement through week 24 observed in 36 out of these 43 patients (83.27%). Multivariate analysis revealed that early achievement of LLDAS was particularly observed in patients with higher baseline lymphocyte counts [HR=1.79, 95% CI (1.19-2.67), P=0.005]and serum albumin levels [HR=1.06, 95% CI (1.003-1.12), P=0.039]. Conversely, hematological involvement [HR=0.48, 95% CI (0.24-0.93), P=0.031] predicted lower attainment of early-achieved LLDAS. The use of telitacicept was associated with a reduced risk of failing to attain early achievement of LLDAS [HR=2.55, 95% CI (1.36-4.79), P=0.004]. Subgroup analyses and interaction tests showed a stable relationship between the telitacicept use and LLDAS achievement. The results remained consistent across all subgroup analyses. Significant differences (P<0.001) were observed in the Kaplan-Meier estimates for LLDAS among risk groups based on the number of identified risk factors. The achievement of LLDAS is attainable in the management of SLE patients undergoing treatment with telitacicept or belimumab in real-life clinical practice. Baseline lymphocyte counts, serum albumin levels, hematological involvement and the use of telitacicept serve as robust predictors for early-achieved LLDAS, helping to identify patients who are likely to benefit on the treatment.

Seasonal vitamin D levels and lupus low disease activity state in systemic lupus erythematosus.

Seasonal variation and sunlight exposure can impact serum vitamin D levels, potentially influencing lupus symptoms. We investigated seasonal vitamin D levels and their correlation with clinical manifestations and disease activity in systemic lupus erythematosus (SLE). Serum 25(OH) vitamin D3 (25(OH)D3) levels were categorised as deficient (25(OH)D3 < 10 ng/mL), insufficient (10-30 ng/mL) and sufficiency (>30 ng/mL) in participants analysed in winter (n = 407) and summer (n = 377). Logistic regression analysis was performed to assess the impact of vitamin D levels on achieving a lupus low disease activity state (LLDAS), stratified by season. The mean serum 25(OH)D3 levels differed significantly between the winter and summer measurement groups (22.4 vs. 24.2 ng/mL; p = .018). The prevalences of vitamin D deficiency, insufficiency and sufficiency in the winter group were 12.8%, 66.6% and 20.6%, respectively, compared with 4.5%, 67.9% and 27.6% in the summer group. Achieving LLDAS was highest in the vitamin D sufficiency group (winter: 56.6%, summer: 55%) and lowest in the vitamin D deficiency group (winter: 15.4%, summer: 13.6%), with significant differences (all p < .001). Multivariate analysis identified SLE disease activity index ≤4, normal anti-double-stranded DNA and vitamin D sufficiency as significant factors for achieving LLDAS in both seasons. Sufficient vitamin D levels are important for achieving LLDAS in patients with SLE during winter and summer. Therefore, physicians should pay attention to the adequacy of vitamin D levels and consider recommending vitamin D supplementation for patients with vitamin D insufficiency.

Predictors of Remission and Low Disease Activity State in Systemic Lupus Erythematosus: Data from a Multiethnic, Multinational Latin American Cohort.

To determine the predictors of remission and low disease activity state (LDAS) in patients with systemic lupus erythematosus (SLE). Three disease activity states were defined: Remission = SLE Disease Activity Index (SLEDAI) = 0 and prednisone ≤ 5 mg/day and/or immunosuppressants (maintenance dose); LDAS = SLEDAI ≤ 4, prednisone ≤ 7.5 mg/day and/or immunosuppressants (maintenance dose); and non-optimally controlled state = SLEDAI > 4 and/or prednisone > 7.5 mg/day and/or immunosuppressants (induction dose). Antimalarials were allowed in all groups. Patients with at least 2 SLEDAI reported and not optimally controlled at entry were included in these analyses. Outcomes were remission and LDAS. Multivariable Cox regression models (stepwise selection procedure) were performed for remission and for LDAS. Of 1480 patients, 902 were non-optimally controlled at entry; among them, 196 patients achieved remission (21.7%) and 314 achieved LDAS (34.8%). Variables predictive of a higher probability of remission were the absence of mucocutaneous manifestations (HR 1.571, 95% CI 1.064-2.320), absence of renal involvement (HR 1.487, 95% CI 1.067-2.073), and absence of hematologic involvement (HR 1.354, 95% CI 1.005-1.825); the use of immunosuppressive drugs before the baseline visit (HR 1.468, 95% CI 1.025-2.105); and a lower SLEDAI score at entry (HR 1.028, 95% CI 1.006-1.051 per 1-unit decrease). These variables were predictive of LDAS: older age at entry, per 5-year increase (HR 1.050, 95% CI 1.004-1.098); absence of mucocutaneous manifestations (HR 1.401, 95% CI 1.016-1.930) and renal involvement (HR 1.344, 95% CI 1.049-1.721); and lower SLEDAI score at entry (HR 1.025, 95% CI 1.009-1.042). Absence of mucocutaneous, renal, and hematologic involvement, use of immunosuppressive drugs, and lower disease activity early in the course of the disease were predictive of remission in patients with SLE; older age was predictive of LDAS.

Using Actigraphy and mHealth Systems for an Objective Analysis ofSleep Quality on Systemic Lupus Erythematosus Patients.

Although sleep alterations can be an important factor contributing to the clinical state of Systemic Lupus Erythematosus, there are no studies to adequately assess sleep quality in this type of disease. The aim of this work is to analyse the sleep quality of Systemic Lupus Erythematous (SLE) patients based on more objective information provided by actigraphy and mobile systems. The idea is to carry out a comprehensive study by analysing how environmental conditions and factors can affect sleep quality. In traditional methods the information for assessing sleep quality is obtained through questionnaires. In this work, a novel method is proposed by combining these questionnaires that provide valuable but subjective information with actigraphy and a mobile system to collect more objective information about the patient and their environment. The method provides mechanisms to detect how sleep hygiene could be associated directly with the sleep quality of the subjects, in order to provide a custom intervention to SLE patients. Moreover, this alternative provides ease of use, and non-intrusive ICT (Information and CommunicationTechnology) through a wristband and a mHealth system. The mHealth system has been developed for environmental conditions sensing. This consists of a mobile device with built-in sensors providing input data about the bedroom environment during sleep, and a set of services of the Environmental Monitoring System for properly managing the configuration, registration and fusion of those input data. In previous studies, this information has never been taken into account. However, the information could be relevant in the case of SLE patients. The sample is composed of 9 women with SLE and 11 matched controls with a mean age of 35.78 and 32.18, respectively. Demographic and clinical variables between SLE patients and healthy controls are compared using the Fisher exact test and the Mann-Whitney U test. Relationships between psychological variables, actigraphy measures, and variables related to environmental conditions are analysed with Spearman's rank correlation coefficient. The SLE group showed poorer sleep quality, and more pain intensity, fatigue and depression than the healthy controls. Significant differences between SLE women and healthy controls in measures of actigraphy were not found. However, the fusion of the measures of the environmental conditions that were collected by the mobile system and actigraphy, has shown that light, and more specifically temperature have a direct relation with several measures of actigraphy which are related to sleep quality. It should be emphasize this result because usually the sleep problems are assessment through self-reported measures which had not revealed this association. Moreover, there are no previous studies that analyse these aspects in bedroom environments of SLE patients directly from objective measures. The results indicate the need tocomplement the subjective evaluation of sleep with objective measures. The use of actigraphy in combination with a new mHealth system provides a complete assessment especially relevant to chronic conditions as SLE. Both systems incorporate this objective information directly from objective measures in a non-intrusive way. Moreover, the measures of bedroom environmental variables provide useful and relevant clinical information to assess what is happening daily and not occasionally. This could lead to more customized interventions and adapt the treatment to each individual.

Thromboelastometry Shows a Prothrombotic State in Systemic Lupus Erythematosus Related to Diminished Fibrinolysis and Microparticle-Derived Tissue Factor

Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disorder of unknown origin with a high mortality pattern due to the development of a premature cardiovascular disease. The presence in these patients of a dysfunctional endothelium together with a hypercoagulable milieu may contribute to an increased incidence of thrombotic events. Increased thrombin generation, elevated levels of circulating microparticles and plasmatic levels of PAI-1 may contribute to the prothrombotic phenotype of the disease but data are scarce.Objectives: 1-To characterize the prothrombotic state in SLE by rotational thromboelastometry (ROTEM) and thrombin generation linked to tissue factor bearing microparticles. 2- To evaluate endothelial damage in patients with SLE and its relationship with the prothrombotic state of the disease. 3- To evaluate the influence of PAI-1 in the prothrombotic state of SLE.Material and methods: 39 patients with SLE and 25 sex and age matched healthy subjects were included. Whole blood was drawn in standard BD sodium citrate tubes (3.2%). ROTEM was performed in naTEM condition. Clotting time (CT, time from start of measurement until initiation of clotting [in seconds], alpha angle, which reflects the rate of fibrin polymerisation (tangent to the curve at 2-mm amplitude [in degrees]), maximum clot firmness, which reflects the maximum tensile strength of the thrombus (MCF, [in mm]), the time that clot takes to increase from 2mm above baseline to 20mm above baseline (CFT) and A5, amplitude at 5 min, were recorded.To evaluate the presence of tissue factor bearing microparticles, thrombin generation was determined by Calibrated Automated Thrombogram (CAT) in presence of 4 mM phospholipid (MP-Reagent, Diagnostica Stago, Spain). The endogenous thrombin potential (ETP, the total amount of thrombin generated over time); the lag time (the time to the beginning of the explosive burst of thrombin generation); the peak height of the curve (the maximum thrombin concentration produced); and the time to the peak were evaluated.Antigenic levels of E-selectin and PAI-1 were determined by ELISA (R&D Systems, MN, USA and Affymetrix eBioscience, Vienna, Austria) respectively.Results: ROTEM parameters showed a hypercoagulable profile in LES patients. CT and CFT were shorter (p<0.001 in both cases), and MCF, alpha angle and A5 were higher (p<0.001, p<0.02 and p<0.001 respectively) when compared to healthy controls. On the other hand, CAT parameters did not show differences between both groups. Nevertheless, in LES patients but not in controls, CAT parameters significantly correlated with ROTEM ones (Table 1). Table 1Correlations in the LES patients group between CAT and ROTEM parameters. Analyses were performed with Spearman test. N: number of determinations; p* denotes significance.CTCFTMCFMCF-talphaA5A10ETP(MP)r-,301-,375*,369*-,368*,378*,364*,393*p,0840,028*0,031*0,032*0,027*0,034*0,021*N34343434343434Peak(MP)r-,353*-,396*,372*-,345*,396*,393*,402*p0,040*0,020*0,030*0,045*0,020*0,021*0,018*N34343434343434ttPeak(MP)r,240,222-,242,217-,223-,209-,210p,171,207,168,217,205,236,232N34343434343434In order to evaluate endothelial damage, plasma E-selectin and PAI-1 were determined. No differences were found in E-selectin level whereas increased PAI-1 levels were seen in LES group (p<0.006). PAI-1 did not correlate to ROTEM parameters.Conclusions: ROTEM can detect a hypercoagulable state in patients with SLE. The hypercoagulable state may be linked to increased tissue factor bearing microparticles and increased PAI-1 plasma levels. DisclosuresNo relevant conflicts of interest to declare.

Association of cerebrospinal fluid anti-Sm antibodies with acute confusional state in systemic lupus erythematosus.

IntroductionNeuropsychiatric manifestation in systemic lupus erythematosus (NPSLE) is one of the most serious complications of the disease. Previous studies revealed the strong association between serum anti-Sm and organic brain syndrome, consisting mainly of acute confusional state (ACS) of diffuse psychiatric/neuropsychological syndromes (diffuse NPSLE). However, the precise mechanism by which anti-Sm causes diffuse NPSLE remains unclear. Of note, recent studies demonstrated that anti-U1 RNP antibodies (anti-RNP) in cerebrospinal fluid (CSF) are associated with NPSLE. The present study was designed to explore the association of anti-Sm antibodies in CSF with NPSLE.MethodsPaired serum and CSF specimens were obtained from 72 patients with NPSLE (49 with diffuse NPSLE, 23 with neurological syndromes or peripheral neuropathy (focal NPSLE) and from 22 control patients with non-SLE neurological diseases. Sera were also obtained from 41 patients with active SLE without neuropsychiatric manifestations (non-NPSLE). Anti-Sm and anti-RNP were measured by enzyme-linked immunosorbent assay (ELISA). Blood-brain barrier (BBB) function and intrathecal anti-Sm production were evaluated by Q albumin and CSF anti-Sm index, respectively. Binding of anti-Sm to neuroblastoma cell lines SK-N-MC and Neuro2a was examined by flow cytometry and by cell ELISA.ResultsAnti-Sm and anti-RNP in CSF and sera were elevated in NPSLE compared with non-SLE control. CSF anti-Sm, but not CSF anti-RNP, was significantly elevated in ACS compared with non-ACS diffuse NPSLE or with focal NPSLE. By contrast, there were no significant differences in serum anti-Sm or anti-RNP among subsets of NPSLE and non-NPSLE. Whereas there were no significant differences in CSF anti-Sm index, Q albumin was elevated in ACS compared with non-ACS or with focal NPSLE. Notably, CSF anti-Sm was correlated with Q albumin (r = 0.2373, P = 0.0447) or with serum anti-Sm (r = 0.7185, P <0.0001) in 72 patients with NPSLE. Finally, monoclonal anti-Sm and purified human anti-Sm bound to the surface of SK-N-MC and Neuro2a.ConclusionsThese results demonstrate that the elevation of CSF anti-Sm through transudation from systemic circulation due to damaged BBB plays a critical role in the pathogenesis of ACS. More importantly, the data indicate that anti-Sm is yet another autoantibody with presumed neural toxicity, but might not be the last.

OP0215 Association of Cerebrospinal Fluid Anti-Sm Antibodies with Acute Confusional State in Systemic Lupus Erythematosus

BackgroundNeuropsychiatric manifestation in systemic lupus erythematosus (NPSLE) is one of the most serious complications of the disease. Previous studies disclosed the strong association between serum anti-Sm antibodies and organic brain...

THU0298 Consensus Definition of a Low Disease Activity State in Systemic Lupus Erythematosus

BackgroundIn systemic lupus erythematosus (SLE), organ damage, morbidity and mortality are the result of acute or sustained disease activity. The diversity of clinical features of active SLE makes quantification of...

Adenosine Inhibits the Release of Arachidonic Acid in Activated Human Peripheral Mononuclear Cells. A Proposed Model for Physiologic and Pathologic Regulation in Systemic Lupus Erythematosus

In the current work, the pathways are presented and reviewed showing how adenosine acts on the production and release of arachidonic acid (AA) in activated human monocytes by the involvement of various phospholipase A2 (PLA2) and protein kinase C (PKC) enzymes in physiological (normal) conditions and in a pathologic state in systemic lupus erythematosus (SLE). Two molecules of activated monocytes mainly determine the actual amounts of AA released: (1) interleukin-1β (IL-1β) increasing and (2) adenosine (Ado) suppressing this process. The AA production of monocytes mainly depends on two (IV and VI) types of PLA2 enzymes. PKCα phosphorylates the cytosolic, Ca-dependent and steroid-sensitive PLA2 (type IV), whereas PKCδ phosphorylates the Ca-independent PLA2 (type VI). By the suppression of IL-1β production in the activated human monocytes, adenosine can decrease the release of AA causing a diminished phosphorylation of both PKC isoenzymes. In SLE monocytes, the disease-specific decreased release of AA that we found earlier could be related to the decreased expression of PKCδ. These pathways are summarized in a proposed model.

Clinical and endoscopic assessment of gastric state in systemic lupus erythematosus and antiphospholipid syndrome

Objective. To characterize gastric mucosa (GM) state in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Material and methods. Gastroscopy (GS) with GM biopsy and histological examination was performed in 85 pts (65 with SLE and 20 with primary APS). 26 from 65 pts with SLE had secondary APS. 21 SLE pt before inclusion did not receive glucocorticoids (GC). H. pylory and its cytotoxicity gen CagA, HSV-I, CMV were examined in GM samples with PCR. Results. The most frequent GS-feature in pts with SLE and ARS was antral gastritis (82%). In 25% of pts erosions and in 8% - hemorrhages of GM were present. Erosions localized mostly in stomach (25%), in 7% of cases they were present in duodenum. In APS pts epigastric pain and GM erosions were more frequent than in SLE without APS. H.pylory in GM was revealed in 70-81%. In 42% of pts it was present in combination with HSV-1 and/or CMV. In more than half of pts with antral gastritis and GM erosions revealed H. pylory was CagA-positive. GC therapy did not influence frequency of GM erosions and hemorrhages formation. Conclusion. The most frequent GS-features in pts with SLE and ARS were antral gastritis and GM erosions. Epigastric pain and GM erosions were more frequent in pts with APS.

Modification of lymphoid and brain nerve growth factor levels in systemic lupus erythematosus mice

In the present work we investigated the production of nerve growth factor (NGF) in the brain and peripheral tissues of female NZB/W F1 mice, a well characterized model of murine lupus. Our results indicate that while no significant difference in the NGF content was observed in the sera and tissues of NZB/W mice and its parental strains during the first months of life, the levels of circulating NGF and the NGF content in the kidneys significantly increase in the autoimmune mice during the development of the disease. The NGF-producing brain regions showed a decrease in NGF concentration in 8 month-old NZB/W mice. Moreover, we found a modification of the NGF concentration in the spleens of autoimmune mice at 5 and 8 months. Our data support the hypothesis of a correlation between NGF and the inflammatory state of systemic lupus erythematosus (SLE) and indicate that NGF could have a role in the pathogenesis of this disease.