Active Systemic Lupus Erythematosus Research Articles

Comparison of quantitative and qualitative anti-dsDNA assays.

In evaluation of systemic lupus erythematosus (SLE), anti-double-stranded DNA antibodies (anti-dsDNA) play a significant role in diagnosis, monitoring SLE activity, and assessing prognosis. However, evaluations of the performance and limitations for recently developed methods for anti-dsDNA assessment are sparse. Specimens used for antinuclear antibody testing (n = 129) were evaluated for anti-dsDNA assay comparability across 4 medical centers in the United States. The methods compared were Werfen Quanta Lite dsDNA, Zeus Scientific dsDNA Enzyme Immunoassay, Bio-Rad multiplex immunoassay (MIA) dsDNA, ImmunoConcepts Crithidia, and Bio-Rad Laboratories Crithidia. For quantitative anti-dsDNA measurements, Spearman's correlation coefficient was highest between Zeus and Werfen (ρ = 0.86; CI, 0.81-0.90; P < .0001). Comparison of MIA to Werfen or Zeus yielded similar results to each other (ρ = 0.58; CI, 0.44-0.68; P < .0001; and ρ = 0.59; CI, 0.46-0.69; P < .0001, respectively), but lower than the correlation between Zeus and Werfen. Positive concordance between assays ranged from 31.4% to 97.1%, and negative concordance between assays ranged from 58.5% to 100%. The detection of anti-dsDNA in those with SLE diagnosis ranged from 50.9% to 77.4% for quantitative assays and 15.1% to 24.5% for Crithidia assays. Current quantitative anti-dsDNA assays are not interchangeable for patient follow-up. Crithidia-based assays demonstrate high negative concordance and lack positive concordance among the methods.

#1843 Deletion of IL17-producing follicular helper T cells restrains the germinal center reaction in systemic lupus erythematosus

Abstract Background and Aims Systemic lupus erythematosus (SLE) is an autoimmune disorder in which autoantibody formation can lead to severe kidney pathology. Interleukin (IL)17-producing T cells have been suggested to play an important role in the pathogenesis of SLE, and IL-17 inhibition was shown to ameliorate SLE pathology in lupus-prone mice. Moreover, the frequency of circulating follicular helper T (Tfh) cells, a T cell subset that orchestrates the maturation of high-affinity antibodies in the germinal center of secondary lymphoid organs, is associated with disease activity in SLE. Increased frequencies of IL17-producing Tfh have been reported in SLE patients compared to controls, but their role in SLE pathogenesis is still unknown. Method By leveraging the B6.Sle1NZM2410/AegYaa strain, we generated lupus-prone mice in which IL17-producing Tfh cells could be either fate-mapped (SLE Tfh17-FM, Il17aCRERosaLoxSTOPLox-YFPSle1+/+Yaa+) or fate-mapped and selectively depleted by intraperitoneal diphtheria toxin (DT) administration (SLE Tfh17-DTR, Il17aCRERosaLoxSTOPLox-YFPCxcr5LoxSTOPLox-DTRSle1+/+Yaa+). Tfh17-FM and Tfh17-DTR mice (both Sle1−/−Yaa−) were used as controls. Results Tfh17 comprised approximately 0.4% of total splenic Tfh in SLE mice at 6 weeks of life, and DT administration caused potent and selective depletion of these cells in the SLE Tfh17-DTR strain (Fig. 1A). Early Tfh17 deletion from week 4 to week 9 did not modify the increased Tfh frequency observed at 20 weeks in SLE mice, but resulted in long-term reduction of splenic germinal center (GC) B cells and plasmacells (Fig. 1B-C). IL17 receptor A was overexpressed in non-GC B cells and plasmacells of SLE mice compared to controls, suggesting a possible increased susceptibility of these subsets to IL17 (Fig. 1D). SLE Tfh17-DTR mice treated with DT displayed a trend towards decreased anti-DNA levels compared to SLE Tfh17-FM (Fig. 1E), but both glomerular immunocomplex deposition and renal pathology were not significantly impacted (Fig. 1F-G). Conclusion The germinal center reaction is affected by selective depletion of IL17-producing Tfh cells in SLE mice, with reduced differentiation of GC B cells and plasmacells. The modest effect of Tfh17 depletion on autoantibody levels and lupus nephritis pathology suggests that other Tfh subsets may play a role in GC-derived autoantibody generation. In addition, extrafollicular sources may also contribute to autoantibody production in SLE.

ITRAQ-based mass spectrometry screen to identify serum biomarkers in systemic lupus erythematosus

ObjectiveSystemic lupus erythematosus (SLE) is a complex systemic autoimmune disorder with no reliable serum biomarkers currently available other than autoantibodies.MethodsIn the present study, isobaric tags for relative and absolute quantitation-based...

#971 Effects of arsenic trioxide on MMP9/IL-17A expression in lupus nephritis—results from bioinformatics analysis and in vitro studies

Abstract Background and Aims Previous research has indicated that ATO treatment at low doses may decrease the likelihood of flares in active systemic lupus erythematosus (SLE) patients, but the pharmacological mechanisms of such effect have not been studied. Method Machine learning and network pharmacology analysis were employed to explore the potential targets from differentially expressed genes (DEGs) of human SLE and LN peripheral blood mononuclear cells (PBMCs) microarray datasets and pharmacological databases. GO and KEGG analyses were performed, and the protein-protein interaction (PPI) network was constructed. The association of these characteristic genes and immune cells were further examined and validated. Results Three machine learning models (RF, SVM, and XGB) were utilized to identify five immunoregulatory genes in SLE among twelve intersection DEGs. Among these genes, MMP9 exhibited the highest ROC AUC (0.92) in predicting disease development. KEGG analysis revealed significant associations with the IL-17 signaling pathway (p = 1.67E-18). Furthermore, ssGSEA analysis indicated positive correlations between MMP9 and macrophages (correlation coefficient 0.88) as well as neutrophils (correlation coefficient 0.66). In vitro treatment of PBMCs from lupus nephritis (LN) patients with ATO resulted in downregulation of MMP9 and IL-17A, validating our bioinformatics findings. Conclusion ATO has the potential to mitigate the MMP/IL-17A pathways in PBMCs in LN patients, and hence maybe a promising and innovative therapeutic alternative.

#2130 Pregnancy in patients with chronic kidney disease stage 3 to 5: what to expect?

Abstract Background and Aims Chronic Kidney disease (CKD) has long been recognized as a risk factor for adverse pregnancy outcomes. Advanced CKD is also associated with decrease fertility, raising the importance of an early approach of pre- menopausal CKD women to discuss pregnancy planning and avoid long term kidney function deterioration or prematurity sequelae in their child-to-be. Method Retrospective analysis of maternal, obstetric and perinatal outcomes of patients with CKD stage 3 to 5, followed by the Nephro-obstetric clinical team between 2011 until 2023. Results We evaluated 31 gestations in 28 patients, with mean age of 32 years [19-43], 21 Caucasian and 7 African, 15 nulliparous, 21/28 with hypertension (HTN), 6/28 diabetic, 2/28 with HIV and 3/28 with systemic lupus erythematosus (SLE). CKD diagnosis occurred during pregnancy in 4/28 patients. Mean pre-pregnancy SCr was 2,1 ± 1 mg/dL [1,1-4,3] and mean proteinuria was 1535 ± 1874 mg/day [5 - 6000], and 11 patients had proteinuria &amp;gt;1 g/day. At gestation baseline, patients evaluated in each pregnancy were in CKD stage 3a (9/31), 3b (10/31), 4 (8/31) and 5 (4/31). CKD etiologies were heterogenous, with most common diagnosis being hereditary nephropathies (7/28), Diabetic nephropathy (6/28) and lupus nephritis (3/28). Exposure to teratogenic therapy occurred in 10/31 gestations (mean time of 11 weeks; 2 - 15), generally ACE/ARBs. Medical termination of pregnancy occurred in 3 gestations due to active SLE and severe growth restriction, 1 abortion at 16 weeks and 1 stillbirth due to cervical insufficiency. HTN aggravation occurred in 16/31 (52%) gestations and de novo proteinuria or proteinuria increase occurred in 7/31(22,5%) and 20/31 (64.5%) gestations, respectively due to pregnancy hyperfiltration, active lupus nephritis and preeclampsia. Considering pregnancies that progressed, renal function (RF) deterioration occurred 10/19 (53%) patients in CKD stage 3 with 20%/60%/20% with full/partial and no RF recovery, respectively. In CKD4 6/7 patients (86%) had RF aggravation with 17% and 83% with partial or no RF recovery. Of the 2 Patients in CKD stage 5 with gestation &amp;gt;20 weeks, 1 started dialysis during pregnancy and the other 4 months postpartum. Dialysis was initiated in 3 patients during pregnancy (2 CKD stage 4 and 1 CKD stage 5) due to urea level &amp;gt;100 mg/dL. RF deterioration was mainly due to pregnancy hyperfiltration and preeclampsia (11/26 gestations; 42%). Mean gestation age at delivery was 34 ± 4 weeks (28-41), with 73% and 53,8% pregnancies with gestational age &amp;lt;37 and 34 weeks, respectively. Mean birth weight was 1866 ± 707 g (555–3095 g), with 73% low birth weight (&amp;lt;2500 g). Mean Apgar 1/5/10 was 9/10/10, respectively. Cesarean was performed in 53,8% gestations and 61,5% newborns were admitted to the neonate care unit (NICU) due to prematurity Conclusion CKD patients with stage 3 to 5 are at increased risk of worse maternal outcomes, namely HTN aggravation (52%), de novo or increase proteinuria (87%) and RF deterioration (53% stage 3 and 86% stage 4) with significant permanent loss of kidney function. Obstetric and perinatal results were also significantly worse with a high incidence of preeclampsia (42%), prematurity (73%), low birth weight (73%) and the need of NICU (61.5%). It is of sum importance, that advanced CKD patients are previously counseled about those risks and are managed in a multidisciplinary feto- maternal clinic experienced in CKD pregnancy care that has a dialysis unit.

#525 SGLT2 inhibition in non-diabetic CKD: results in experimental lupus nephritis

Abstract Background and Aims Sodium glucose cotransporter type 2 inhibitors (SGLT2i) potently attenuate cardiovascular morbidity and progression of CKD in patients with type 2 diabetes. It has been proposed that SGLT2 inhibition may also elicit renoprotective effects in non-diabetic CKD. The aim of this work is to evaluate whether the treatment with an SGLT2i improves kidney disease progression in a mouse model of lupus nephritis (LN). Method We performed a single center randomized controlled preclinical trial using female MRLlpr/lpr mice. The animals were randomly assigned to (1) vehicle or (2) empagliflozin (EMP, 10 mg/kg/day) treatment once signs of active systemic lupus erythematosus (SLE) appeared: proteinuria &amp;gt;100 mg/dL (++ in reactive strips) or lymphadenopathy in minimum 2 bilateral sites with proteinuria &amp;gt;30 mg/dL (+ in reactive strips). We included 13 mice per group that were treated during 4 weeks. Empagliflozin was given as an admix into standard chow diet. Reduction of urinary albumin to creatine ratio (UACR) was considered the primary endpoint whereas glomerular filtration rate (GFR), renal histology (LN activity/chronicity index, glomerulosclerosis, interstitial fibrosis) and SLE markers (total serum IgG, anti-dsDNA IgG, glomerular IgG deposits, lymph node weight, spleen weight) were considered secondary endpoints. Results After 4 weeks of treatment, no significant differences in fasting blood glucose levels were found between the experimental groups. As expected, empagliflozin administration notably inhibited SGLT2 in the tubular cells demonstrated by a significant increase of urinary glucose (p &amp;lt; 0.0001). This is consistent with the increased water intake observed in MRLlpr/lpr mice treated with empagliflozin (p &amp;lt; 0.0001). At the end of the experiment, vehicle treated MRLlpr/lpr mice showed a significant increase in UACR (p = 0.0012) consistent with LN progression that was not attenuated by empagliflozin. In line, empagliflozin did not modify GFR and LN activity/chronicity indexes, glomerulosclerosis or interstitial fibrosis in kidney. Finally, regarding SLE markers, 4-weeks empagliflozin treatment was not able to decrease total serum IgG, anti-dsDNA IgG, glomerular IgG deposits or lymph node weight. Only spleen weight was significantly decreased in empagliflozin treated MRLlpr/lpr mice (p = 0.003). Conclusion In our experimental setting, empagliflozin treatment reduced spleen weight suggesting a protective role in SLE in MRLlpr/lpr mice. However, empagliflozin did not modify LN progression in MRLlpr/lpr mice probably because the acute LN phase. It is expected that the positive effect in terms of reducing proteinuria will be observed in patients with LN and residual proteinuria

Active but not quiescent lupus nephritis during pregnancy is associated with a higher rate of adverse obstetric outcomes: Analysis of a prospective cohort.

To compare the maternal-fetal/neonatal outcome in patients with systemic lupus erythematosus (SLE) with and without lupus nephritis (LN) in remission or with active disease. A prospective cohort of pregnant patients with SLE (ACR 1997 criteria) was studied from January 2009 to December 2021. Demographic, clinical, biochemical, and immunological variables as well as the usual maternal-fetal/neonatal complications were recorded. We compared four groups according to the status of SLE during pregnancy: patients with quiescent SLE without lupus nephritis, patients with active SLE without lupus nephritis, patients with quiescent lupus nephritis, and patients with active lupus nephritis. Statistical analysis included descriptive statistics, bivariate analysis, and Cox regression analysis. A total of 439 pregnancies were studied, with a median age of 28 ± 6, SLE duration of 60 months (interquartile range 36-120). A higher frequency of maternal and fetal/neonatal complications was observed in patients with active SLE with or without lupus nephritis. Multivariate analysis showed that active LN was a risk factor for gestational hypertension (hazard ratios [HR] 1.95; 95% confidence intervals [CI]: 1.01-6.39), premature rupture of membranes (HR 3.56; 95% CI: 1.79-16.05) and more frequent cesarean section (HR 1.82; 95% CI: 1.13-2.94). LN is associated with a higher frequency of maternal complications, especially in those patients with active disease during pregnancy, and those maternal complications had an impact on poor fetal/neonatal outcomes. Strict control and timely care of LN could improve the obstetric prognosis.

Identification of immune subsets with distinct lectin binding signatures using multi-parameter flow cytometry: correlations with disease activity in systemic lupus erythematosus.

Cell surface glycosylation can influence protein-protein interactions with particular relevance to changes in core fucosylation and terminal sialylation. Glycans are ligands for immune regulatory lectin families like galectins (Gals) or sialic acid immunoglobulin-like lectins (Siglecs). This study delves into the glycan alterations within immune subsets of systemic lupus erythematosus (SLE). Evaluation of binding affinities of Galectin-1, Galectin-3, Siglec-1, Aleuria aurantia lectin (AAL, recognizing core fucosylation), and Sambucus nigra agglutinin (SNA, specific for α-2,6-sialylation) was conducted on various immune subsets in peripheral blood mononuclear cells (PBMCs) from control and SLE subjects. Lectin binding was measured by multi-parameter flow cytometry in 18 manually gated subsets of T-cells, NK-cells, NKT-cells, B-cells, and monocytes in unstimulated resting state and also after 3-day activation. Stimulated pre-gated populations were subsequently clustered by FlowSOM algorithm based on lectin binding and activation markers, CD25 or HLA-DR. Elevated AAL, SNA and CD25+/CD25- SNA binding ratio in certain stimulated SLE T-cell subsets correlated with SLE Disease Activity Index 2000 (SLEDAI-2K) scores. The significantly increased frequencies of activated AALlow Siglec-1low NK metaclusters in SLE also correlated with SLEDAI-2K indices. In SLE, activated double negative NKTs displayed significantly lower core fucosylation and CD25+/CD25- Siglec-1 binding ratio, negatively correlating with disease activity. The significantly enhanced AAL binding in resting SLE plasmablasts positively correlated with SLEDAI-2K scores. Alterations in the glycosylation of immune cells in SLE correlate with disease severity, which might represent potential implications in the pathogenesis of SLE.

Relationship of serum and dietary vitamin D with high cardiometabolic risk in Mexican systemic lupus erythematosus patients: A cross-sectional study.

Objetive: Serum and dietary vitamin D could influence clinical disease activity and cardiometabolic outcomes in systemic lupus erythematosus (SLE). This study aimed to assess the relationship of serum and dietary vitamin D with cardiometabolic risk in Mexican SLE patients and healthy subjects (HS).Methods: 224 SLE patients and 201 HS were included in this cross-sectional study. Serum calcidiol was measured using a competitive enzyme-linked immunosorbent assay (ELISA). Vitamin D dietary intake was assessed by collecting three 24h food records. Dietary patterns (DPs) were identified using principal component analysis (PCA). Cardiometabolic status was analyzed through biochemical measurements and cardiometabolic indexes.Results: Calcidiol deficiency (<20 ng/mL) was associated with 1.66-fold higher risk of excess weight by body mass index (BMI) (≥25 kg/m2) (p = .02), 2.25-fold higher risk to low high-density lipoprotein-cholesterol (HDL-C) (<40 mg/dL) (p < .001), and 1.74-fold higher risk to high triglycerides (TG) ≥150 mg/dL (p = .02). Inadequate vitamin D dietary intake was associated with 1.92-fold higher risk of presenting non-healthy waist circumference (WC) (>80 cm) (p < .01), 2.05-fold higher risk of android waist to hip ratio (WHR ≥85) (p < .01), and 1.72-fold higher risk to excess weight (p = .02). Non-adherence to a DP rich in vitamin D food sources was associated with higher WC, WHR, triglycerides, and lower high-density lipoprotein-cholesterol (HDL-C); furthermore, in HS, non-adherence to the DP rich in vitamin D food sources provided 2.11-fold higher risk to calcidiol deficiency.In Cconclusion: A pattern of Calcidiol deficiency, inadequate vitamin D dietary intake, and non-adherence to a DP rich in vitamin D food sources was related to high cardiometabolic risk in SLE patients and HS.

Methylprednisolone Pulses and Prolonged Remission in Systemic Lupus Erythematosus: A Propensity Score Analysis of the Longitudinal Lupus-Cruces-Bordeaux Inception Cohort.

The objective of this study was to analyze the effect of methylprednisolone pulses (MP), given during the first year after the diagnosis of systemic lupus erythematosus (SLE), in achieving prolonged remission according to the degree of lupus activity at presentation. We conducted an observational study of routine clinical care data from the Lupus-Cruces-Bordeaux cohort. The end point was prolonged remission (ie, during five consecutive yearly visits). The effect of MP on remission during the first year was analyzed in the whole cohort and according to the baseline Systemic Lupus Erythematosus Disease Activity Index 2000 score: <6, 6 to 12, and >12, reflecting mild, moderate, and severe activity, respectively. For adjustment, logistic regression with propensity score (PS) and other therapeutic covariates was performed. Two hundred thirty-three patients were included. Prolonged remission was achieved by 132 patients (57%). MP were associated with prolonged remission (PS-adjusted odds ratio [OR] 2.50, 95% confidence interval [CI] 1.04-623, P = 0.042). A strong clinical effect was seen among patients with moderate (adjusted OR 5.28, 95% CI 1.27-21.97, P = 0.022) and moderate-severe SLE activity (adjusted OR 4.07, 95% CI 1.11-14.82, P = 0.033). The administration of MP resulted in reduced average dosages of prednisone during the first year among patient with moderate (mean 6.6 vs 10.2 mg/day, P = 0.017) and severe activity (mean 14 vs 28 mg/day, P = 0.015). The odds of prolonged remission were increased by longer-term use of hydroxychloroquine (HCQ) and decreased by higher initial doses of prednisone. This study supports the use of MP to induce prolonged remission in patients with SLE, particularly in those with moderate and severe activity. The extended use of HCQ also contributes to achieve prolonged remission.

Evaluation of a novel particle-based assay for detecting SLE-related autoantibodies

Anti-dsDNA, anti-Sm, and anti-ribosomal-P autoantibodies are hallmarks of systemic lupus erythematosus (SLE), being anti-dsDNA and anti-Sm included in 2019-ACR/EULAR SLE-Classification Criteria. Enzyme-linked (ELISA) and chemiluminescence assays (CIA) are widely established in immunology laboratories, but new technologies, such as particle-based multi-analyte technology (PMAT), are nowadays available. The present study aimed to compare the presence of anti-dsDNA and anti-Sm autoantibodies measured by CIA and PMAT and analyze diagnostic and clinical SLE activity performance. Anti-ribosomal-P autoantibodies by PMAT were also included. Consequently, anti-dsDNA and anti-Sm detected by CIA showed substantial agreement with PMAT (Cohen's kappa = 0.662 and 0.671, respectively). Anti-dsDNA autoantibodies measured by PMAT showed a positive correlation with clinical SLEDAI-2K (p < 0.001) and a negative correlation with complement consumption (p < 0.001). Anti-Sm and anti-ribosomal-P autoantibodies showed a positive correlation with SLEDAI-2K (p < 0.001 and p = 0.001, respectively) and a negative correlation with complement consumption (p < 0.001 and p = 0.001, respectively). Finally, anti-Sm autoantibodies were associated with renal involvement (p < 0.05).

Concomitant Moderate to Severe Cutaneous Lesions Have Marked Impact on Quality of Life in Patients with Active Systemic Lupus Erythematosus: A Cross-Sectional Insight from Two Phase 3 Randomised Clinical Trials in Adults.

For the first time and in a large study we have shown that patients with active SLE, HRQoL were negatively affected by the presence of moderate/severe skin lesions compared to patients with active SLE with no/mild skin lesions.

Indexes of skin activity and damage in patients with systemic lupus erythematosus – CLASI and R-CLASI

Introduction. Cutaneous Lupus Disease Area and Severity Index (CLASI) and its modified version, the Revised Cutaneous Lupus Erythematosus Disease Areas and Severity Index (R-CLASI) are tools for quantifying skin and mucosal lesions in patients with both cutaneous lupus erythematosus and its systemic variant. Evaluation of the scales of activity and skin damage in systemic lupus erythematosus (SLE) is associated with the need to stratify their quantitative characteristics. The Cutaneous Lupus Disease Area and Severity Index (CLASI) and its modified version the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (R-CLASI) are a tool for quantifying skin and mucosal lesions in patients with both cutaneous lupus erythematosus (CLE) and its system version.Objective. To validate the indexes of objective assessment of skin activity and damage CLASI and R-CLASI in the Russian cohort of patients with systemic lupus erythematosus and compare it with dermatological assessments of the quality of life.Material and methods. The study included 55 patients with SLE with various types of skin and mucosal lesions, the median age was 30.0 [26.0; 40.0] years, the duration of the disease was 7.0 [3.0; 14.0] years. To assess the active (reversible) lesion and irreversible skin damage, the CLASI and R-CLASI indexes were used, for the general assessment of activity and damage in SLE, the SLEDAI-2K and SLICC/ACR DI were used.Results. The most common variant of skin lesions in patients with SLE is acute cutaneous lupus erythematosus (ACLE) – 45%, as well as alopecia, which occurs in 62% of cases. The median activity index for CLASI was 5.0 [2.0; 11.0], and R-CLASI was 7.0 [3.0; 18.0]; the median damage index for CLASI was 5.0 [2.0; 11.0], and R-CLASI was 2.0 [0.0; 7.0]. A significant relationship was revealed between the medians of CLASI and R-CLASI scores depending on the degree of activity according to SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index) and the damage Index (DI) in SLE (SLICC/ACR DI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) when recalculating these indexes only for skin and mucous lesions. According to the ROC analysis, the CLASI and R-CLASI skin activity and damage indices showed high sensitivity (CLASI activity index – 98%, R-CLASI – 93%, CLASI and R-CLASI damage index – 91%) and specificity (CLASI activity index – 64%, R-CLASI – 71%, CLASI and R-CLASI damage index – 86%).Conclusion. To assess the severity of skin and mucosal lesions in patients with SLE in the Russian Federation, it is reasonable to use the CLASI and R-CLASI indices. The CLASI and R-CLASI indices reflect the level of activity and severity of skin lesions, with higher values of these indices indicating more severe skin lesions and a significant impact on the overall well-being of SLE patients. Patients with high values of these indices often experience feelings of embarrassment, discomfort, difficulty in performing daily tasks, and limitations in social life. To assess the severity of skin and mucous lesions in patients with SLE in the Russian Federation, it is advisable to use the CLASI and R-CLASI indexes.

Evaluation of Serum Amyloid A and some Biochemical markers in Iraqi patients with systemic lupus erythematosus

An autoimmune condition called systemic lupus erythematosus (SLE) is caused by long-term inflammation. Amyloid A (AA) amyloidosis results in nephropathy and other internal symptoms, including death. The current study set out to look at the relationship between serum amyloid A (SAA) levels in circulation and SLE patients. Methods: Sixty SLE patients and 30 healthy with age range (19-55) yearswere involved in this study. A SLE patient wasidentified in the teaching hospital in Baghdad. In this study, laboratory indicators such as blood lipid, kidney function, test results, and total cholesterol (TC), triglyceride (TG), SAA, and ALB were assessed using an automated biochemical analyzer. Results: Patients with active SLE had serum amyloid A (SAA) values 5.83 mg/L [IQR: 2.08–10.87], 4.92 mg/L [IQR: 1.57–11.43], and 1.33 mg/L [IQR: 0.13–3.12], respectively, substantially upper than personswith inactive SLE or healthy control subjects (P &lt; 0.001). ESR values in healthy control subjects, patients with inactive SLE, and patients with active SLE. In conclusion, the current study's findings offered more proof of SAA's potential involvement in SLE and suggested that it might be valuable biomarkers that could reveal more details about the disease's activity.

P160 High levels of CD19 expression is a characteristic feature of age-associated B cells in ageing and autoimmunity

Abstract Background/Aims Recent evidence implicates an important role for age-associated B cells (ABCs), defined as CD19+IgD-CD27-T-bet+ B cells, in healthy ageing, following viral infection and in active SLE. We know that co-receptors of the B cell receptor (BCR) such as CD19 and other activating receptors can influence B cell activation through distinct pathways. Therefore, we compared the expression of CD19 in B cell subpopulations including ABCs in ageing and SLE. Methods Peripheral blood was obtained from six young (&amp;lt;45 years) healthy participants, seven elderly (&amp;gt;65 years) healthy participants and eight patients with SLE (25-65 years). We performed flow cytometry on peripheral blood mononuclear cells to analyse the expression of extracellular and intracellular markers. We performed statistical analysis using GraphPad Prism v7. Results CD19hi B cell frequency was at least 10-fold higher in T-bet+ cells as a whole and particularly enriched in IgD-CD27-T-bet+, ABCs, in all groups, p &amp;lt; 0.05. The geometric mean fluorescent intensity (gMFI, expression) of CD40 was significantly lower in IgD-CD27-T-bet+ subpopulations compared to IgD-CD27-T-bet- B cell subpopulations in all groups (Table). In all groups, in CD19+T-bet+ cells, compared to CD19+T-bet- cells, there was a significantly increased frequency of IFNγR+ cells, TLR4+ cells, TLR7+ cells and TLR9+ cells (p &amp;lt; 0.05 for all) with remarkable difference noted in SLE patients for TLR7 and TLR9, p &amp;lt; 0.01 (Table). In the switched memory IgD-CD27+ and ABCs, TLR7 expression was significantly higher (p &amp;lt; 0.01) in SLE patients (mean 43.8% and 18.5% respectively) compared to elderly participants (mean 13.5% compared to 4.3% respectively). Conclusion High levels of expression of CD19 is a characteristic feature of ABCs and CD19hiT-bet+ cells predominantly belong to the IgD-CD27-T-bet+ ABC subpopulation. CD19hi IgD-CD27-T-bet+ cells also had significantly lower expression of CD40 and higher expression of IFNγR and TLR7 and TLR9, suggesting that CD19 plays a significant role in moderating activation of ABCs triggered through T-independent, IFNγR-TLR-T-bet pathway. Taken together with the significant role of CD19 in regulating signalling threshold of B cell activation, and its stable expression across different B cell developmental stages, these data provide compelling mechanistic rationale for targeting CD19 to deplete B cells, including potentially pathogenic age-associated, in autoimmune disease such as SLE. Disclosure K. Shah: None. V. Poon: None. S.J. Taylor: None. C. Klein: Corporate appointments; CK is employed by Roche. Shareholder/stock ownership; CK has patents and stock ownership at Roche. F. Kollert: Corporate appointments; FK is employed by Roche. Shareholder/stock ownership; FK has stock ownership at Roche. F. Schuler: Corporate appointments; FS is employed by Roche. Shareholder/stock ownership; FS has patents and stock ownership at Roche. S. Mathur: None. M. Castelino: None. D. Sen: None. J. Cambridge: None. M. Cragg: None. M. Leandro: None. A. Akbar: None. V. Reddy: None.

P158 Cutaneous vasculitis in systemic lupus erythematosus: trends of incidence and risk factors

Abstract Background/Aims Cutaneous vasculitis (CV) is the most common form of vasculitis observed in patients with SLE; however, the precise epidemiological trends and underlying risk factors remain uncertain. The aim of this study was to define the incidence, prevalence, and risk factors of CV in systemic lupus erythematosus (SLE) patients over a period of 20 years. Methods The Birmingham Lupus Cohort is a longitudinal observational cohort of patients with SLE. All patients fulfilled the 1997 ACR Updated Classification Criteria for SLE. Inception patients were recruited within three years of their fourth ACR criterion. Disease activity was assessed using the classic BILAG index and laboratory results recorded. The BILAG vascular domain was used to determine the incidence rate, which refers to the rate at which new cases of minor and major CV attributed to active SLE occur. Cox proportional hazards frailty models were developed to identify clinical and laboratory variables associated with development of CV. Results We analysed 392 patients, of whom 375 (92.5%) were females. There were 213 (55.0%) White, 72 (18.6%) African-Caribbean, 82 (21.1%) South Asian, 9 (2.3%) East Asian, and 11 (2.8%) other ethnicities. The median (IQR) age at enrolment was 33 (26 - 44) years and the median duration of follow up was 9.2 (5.1 - 14.7) years. The incidence rates of minor and major CV were reported in Table 1. In Cox proportional hazards models, there was a positive association between CV and discoid rash (hazard ratio [HR] 2.16 [95% CI: 1.01, 4.61]), Raynaud’s phenomenon (HR 5.67 [95% CI: 4.11, 7.81]), livedo reticularis (HR = 4.69 [95% CI: 1.83, 12.0]), arthritis (HR 3.02 [95% CI: 2.20, 4.15]), renal involvement (OR 2.40 [95% CI: 1.55, 3.71]), haematological involvement (HR = 2.46 [95% CI: 1.80, 3.36]), and Afro-Caribbean descent (HR 1.96 [95% CI: 1.03, 3.74]). In addition, CV was positively associated with anti-dsDNA (HR = 2.33 [95% CI: 1.67, 3.27]), low C3 or C4 (HR 2.29 [95% CI: 2.18, 4.10]), and history of anti-Ro or anti-La (HR = 1.92 [95% CI: 1.15, 3.21]). Conclusion The incidence rates of CV decrease over the duration of follow-up and are associated with defined clinical and serological features. Disclosure A. Saleh: Grants/research support; A.S. is a sponsored PhD student by the Egyptian ministry of higher education represented by The Egyptian Bureau for Cultural &amp; Educational Affairs in London. C. Gordon: None. J. Reynolds: None.

P026 Neurofascin antibodies complicating a case of severe systemic lupus erythematosus

Abstract Background/Aims Juvenile-onset systemic lupus erythematosus (jSLE) is an autoimmune disease that results in increased disease activity and damage compared to adult-onset SLE. There is increased medication burden, severe organ manifestations and higher incidence of renal, cardiovascular and neuropsychiatric (NP) involvement. Anti-nervous system (NS) antibodies are seen across immune mediated diseases including SLE. Myelin oligodendrocyte glycoprotein (MOG) and neurofascin (NF) 186 antibodies are particularly associated with higher frequencies of NP-SLE. These patients can present with the distinct clinical phenotype associated with that antibody (i.e., demyelination with MOG, neuropathy with NF186). Methods We present an SLE patient with progressive neurological features and anti-NF antibodies who responds well to ocrelizumab after modest response to initial immunotherapy. Results An 18 year old female has active jSLE including malar rash, alopecia, arthralgia, aphthous ulcers, headaches. She presents with lower limb and ascending abdominal paraesthesia and left 6th cranial nerve palsy alongside a recent respiratory tract infection. ANA 1:5120 homogenous pattern, high dsDNA, low C3 and C4, thrombocytopenia and antibodies to Sm, Ro, RNP, anti-Rib-P and strongly positive lupus anticoagulant antibodies and low titre anti-cardiolipin (aCL) IgG and IgM. Lumbar puncture is unremarkable. Nerve conduction studies (NCS) demonstrate progressive predominant motor inflammatory neuropathy without demyelination. CT, MRI brain and MRI spine are normal. She is treated as atypical Guillain-Barre Syndrome (GBS)/ Miller-Fischer with 5 days IV immunoglobulin 2g/kg and also for active SLE with 3 days 500mg IV methylprednisolone. She is intubated following worsening dysphagia, dysarthria, muscle weakness and reduced consciousness. Plasma exchange and pulsed cyclophosphamide are subsequently given. Eye and facial movements worsen with NCS showing worsening patchy axonal sensorimotor polyneuropathy. Serial MRI brain is suggestive of posterior reversible encephalopathy syndrome (PRES). Autonomic instability is seen with labile blood pressure and tachycardia. Given the unusual presentation, anti-NF antibodies are tested and identified at 1:3200 positive, NF155 and 186, both IgG1 and IgG2. Given previous adverse reaction to rituximab, she received ocrelizumab which lead to a marked improvement in her sensorimotor symptoms and functionality. C3 and C4 levels show considerable improvement which is sustained and dsDNA levels normalise. B cell depletion therapy was chosen following a small case series of patients with neurofascin antibodies who developed severe autoimmune neuropathies. Half of these patients responded well to rituximab. One proposed mechanism being the targeting of immature CD20+ B cells inhibits plasmablast generation, which may be responsible for neurofascin antibody production early on in the disease. Conclusion Anti-NS antibodies are seen in SLE patients and their presence can suggest increased frequency of NP-SLE suggesting a potential future role as a biomarker. One should consider anti-NF antibody testing in patients with a GBS-like illness with progressive neuropathy, respiratory involvement and autonomic dysfunction despite standard immunotherapy. Disclosure P. Yee: None. M. Mouyis: None.

The role of vitamin D in pediatric systemic lupus erythematosus - a double pawn in the immune and microbial balance.

Having increased popularity during the Covid-19 pandemic, vitamin D3 is currently impressing thanks to the numerous researches aimed at its interactions with the body's homeostasis. At the same time, there is a peak in terms of recommendations for supplementation with it. Some of the studies focus on the link between autoimmune diseases and nutritional deficiencies, especially vitamin D3. Since the specialized literature aimed at children (patients between 0-18 years old) is far from equal to the informational diversity of the adult-centered branch, this review aims to bring up to date the relationship between the microbial and nutritional balance and the activity of pediatric systemic lupus erythematosus (pSLE). The desired practical purpose resides in a better understanding and an adequate, individualized management of the affected persons to reduce morbidity. The center of the summary is to establish the impact of hypovitaminosis D in the development and evolution of pediatric lupus erythematosus. We will address aspects related to the two entities of the impact played by vitamin D3 in the pathophysiological cascade of lupus, but also the risk of toxicity and its effects when the deficiency is over supplemented (hypervitaminosis D). We will debate the relationship of hypovitaminosis D with the modulation of immune function, the potentiation of inflammatory processes, the increase of oxidative stress, the perfusion of cognitive brain areas, the seasonal incidence of SLE and its severity. Finally, we review current knowledge, post-pandemic, regarding the hypovitaminosis D - pSLE relationship.

The first clinical experience with selective DNA plasmasorption using the NucleoCapture Device in the treatment of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology characterized by the overproduction of autoantibodies against various components of the nucleus of the patient's own cells with the development of immunoinflammatory tissue damage. In recent years, more and more data have accumulated on the involvement of neutrophils in the development of the clinical symptoms of SLE, and DNA-containing structures and neutrophil extracellular traps (NETs) playing an important role in this process. Effective neutralization of NETs in SLE can be achieved by removing circulating proteins and molecules associated with NETs from the bloodstream by selective plasma sorption of DNA using the NucleoCapture Device.This article describes the case of a patient who underwent three plasma sorption sessions aiming to suppress the activity of SLE. During the therapy, significant positive dynamics were achieved: the SLEDAI-2K index decreased from 32 to 12 points, the number of leukocytes in the blood normalized, renal function improved, and the immunological activity of the disease decreased.

The role of repeat kidney biopsy in patients with lupus nephritis (case report)

Lupus nephritis (LN) occurs in 35–60% of patients with systemic lupus erythematosus (SLE), often in the early stages of the disease. LN is one of the most severe manifestations of SLE and, if not treated promptly and effectively, can lead to rapid and severe loss of kidney function. Despite modern pharmacotherapy, 5–20% of patients develop end-stage renal failure within 10 years of diagnosis of LN. The main principle of LN therapy is to prevent deterioration of renal function, but a consensus on outcome assessment criteria and clinically relevant short- and long-term goals for LN therapy has not yet been reached. There is increasing evidence of the importance of repeat kidney biopsies to assess the outcomes of the initial phase of therapy and to determine the long-term prognosis of renal failure. It is believed that the information obtained from repeat biopsies can help to make optimal treatment decisions and thus increase the likelihood of achieving a complete renal response in the short term and a more favorable renal prognosis in the long term.We describe a clinical case of a young patient with highly active SLE and morphologically confirmed class IV-S LN. Repeat biopsy and clinical and laboratory examination, had confirmed a clinical and laboratory remission of the disease on the background of the therapy. This made it possible to reduce the dose of methylpednisolone and cytostatic drugs (mycophenolate mofetil) and to discontinue therapy with biologic diseasemodifying antirheumatic drug (rituximab).