Systemic Lupus Erythematosus Pts Research Articles

AB0306 OBESITY PHENOTYPES IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS

Background:The so-called “obesity paradox” when cardiovascular risk is lower in overweight compared to lean patients accompanies some chronic conditions. A possible explanation for this phenomenon comes from variability of obesity phenotypes, i.e., “classical” obesity as exemplary perception of obesity is equal to increased body mass index (BMI) and metabolic disorders; but there are also “metabolically healthy” overweight individuals (increased BMI without metabolic disorders), and “latent” obesity phenomenon (when normal weight is associated with metabolic disorders, especially with insulin resistance (IR) and adipocytokines imbalance). Serum leptin concentrations increase has been established in obese, therefore, this adipocytokine synthesized in adipose tissue, can be used as a marker of body fat mass. Higher cardiovascular risks are known even in young patients with systemic lupus erythematosus (SLE), but obesity phenotypes have not been studied.Objectives:To find out the rate of various obesity phenotypes and to identify factors contributing to “latent” obesity in SLE pts without diabetes mellitus (DM) or hyperglycemia.Methods:A total of 49 SLE pts (46 women, 3 men, 40 [33;48] years old) without established DM or hyperglycemia were enrolled in the study. The median disease duration was 3,0[0,7;8,0] years, SLEDAI-2K was 5[2;8]. SLE pts were treated with glucocorticoids (GC) (84%) and hydroxychloroquine (78%), immunosuppressive drugs (20%) and biological agents (10%). Insulin levels were measured using electrochemiluminescence assay Elecsys (Roche Diagnostics), serum leptin concentrations were estimated using ELISA (DBS-Diagnostics Biochem Canada Inc.). IR was defined as Homeostasis Model Assessment of Insulin Resistance index (HOMA-IR) ≥2,77. Leptin levels were considered elevated at values ≥11,1 ng/ml for women, ≥5.6 ng/ml for men. The overweight / obesity status was determined by World Health Organization criteria in patients with body mass index (BMI) ≥25kg/m2.Results:Overweight / obesity were established in 45% of pts, normal BMI was in 55% of SLE pts. The combination of IR and high leptin levels was found in 32% of overweight / obese pts and 11% of pts with normal BMI (p=0,2), an isolated increased leptin levels - in 64% and 41%, respectively (p=0,1). Metabolic disturbances were absent in 4% of overweight pts and 48% of pts with a normal BMI (p=0,001). Thus, “classical” obesity was found in 43% of cases, “metabolically healthy” obesity - in 2%, and “latent” obesity - in 29% of SLE pts. Leptin levels correlated with BMI (r=0,5, p=0,02), waist circumference (r=0,5, p=0,02) in the overweight / obesity group, and with disease duration (r=0,5, p=0,02), SLEDAI-2K (r=-0,6, p=0,002), anti-dsDNA (r=-0,7, p<0,001), C3 complement (r=0,5, p=0,01), maximum (r=0,7, p<0,001) and current GCs doses (r=0,4, p=0,03) in patients with normal weight. There was a trend to association between leptin levels and duration of GCs therapy in SLE pts with normal BMI (r=0,4, p=0,06).Conclusion:Metabolic disorders - most often increased leptin levels - were diagnosed in the majority of overweight / obese patients, as well as in about 50% of SLE patients with normal weight. There were only isolated cases of “metabolically healthy” obesity in SLE patients. Metabolically obese normal weight (“latent” obesity) phenotype was strongly associated with GCs therapy and decreased disease activity.Disclosure of Interests:None declared

AB0284 COMBINATION THERAPY WITH RITUXIMAB AND BELIMUMAB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Objectives:To assess the efficacy of combined therapy with rituximab (RTM) and belimumab (BLM) in patients with active systemic lupus erythematosus (SLE).Methods:The study included 12 SLE pts (1М/11F) with severe (SLEDAI2K≥10 – 8pts.) and moderate (SLEDAI2K<10- 4pts.) disease activity; out of them 5 patients had lupus nephritis, vasculitis and 7 had predominantly mucocutaneous and articular manifestations of SLE. The dose of oral GC was: 60 mg in one patient with vasculitis, LN, cerebrovasculitis; in 9 patients from 10 to 5 mg; in 2 patients without oral glucocorticoids. All patients with SLE with kidney damage, CNS, and vasculitis received cytostatics. All patients with vasculitis, LN, etc. received mycophenolate mofetil or cyclophosphamide. Rituximab (RTM) was administered at 500-2000 mg, with subsequent adding of Belimumab (BLM) 1-6 months later at a standard dosing regimen 10 mg/kg once a month a total of 7 infusions. The following parameters were evaluated: the effectiveness of therapy, the concentration of autoantibodies, the dose of oral corticosteroids initially at the time of RTM administration and then every 3 months after the initiation of BLM therapy.Results:8 pts demonstrated the decrease in clinical and laboratory SLE activity, starting from 3mo of follow-up. After the start of BLM infusions, a decrease in SLE activity was observed in all patients. Among them, 9 had SLEDAI-2K activity of less than 4 points (SLEDAI-2k Me 12 [9,5;17], after treatment of RTM and BLM 4[2;4]). Only one patient (№4) had a relapse of SLE, due to the omission of the BLM infusion. He was receiving standard GC doses. In dynamics, a decrease anti-double DNA titres (Me 101 [39;250]U/ml vs 19 [9;70] U/ml), С3 (0,44 [0,39;0,59]g/l vs 0,81 [0,72;0,87] g/l), С4 (0,06 [0,031;0,1] g/l vs 0,14 [0,13;0,14] g/l) was registered. The GC dose was reduced in most patients (tab. 1), but the previously prescribed immunosuppressive therapy continued. There were no cases of severe infection.Conclusion:Combination therapy allows to gain control over disease activity in short time, due to the effect of RTM, while added BLM provides further prolongation of the effect achieved, minimizing the risk of flare. The use of such therapy contributes to a rapid and effective reduction in the activity of the disease, normalization of laboratory markers of SLE (at to ds-DNA, C3, C4), the use of lower doses of oral GCs. This combination may be used as a method of choice in pts with severe SLE involving vital organs, and in persistent cutaneous-articular disease and high immunological activity.Table 1.Dose of oral glucocorticoids (prednisone), mg№ patientBefore the introduction of RTM, mg1st 7th injection of of BLM, mg7th injection of BLM, mg1202015↓27,555↓3555=4101010↓5555=6607,52,5↓↓↓7102,50↓↓↓810105↓92,52,52,5=1010105↓11000=12000=Disclosure of Interests:None declared

OP0132 EFFECT OF IBERDOMIDE ON CUTANEOUS MANIFESTATIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS OF A 24-WEEK, PLACEBO-CONTROLLED, PHASE 2 STUDY

OP0132 EFFECT OF IBERDOMIDE ON CUTANEOUS MANIFESTATIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS OF A 24-WEEK, PLACEBO-CONTROLLED, PHASE 2 STUDY

OP0045 DELINEATION OF A PROINFLAMMATORY CYTOKINE PROFILE TARGETED BY JAK1/2 INHIBITION USING BARICITINIB IN A PHASE 2 SLE TRIAL

Background:Given the unmet clinical needs in systemic lupus erythematosus (SLE), including poor disease control and drug toxicities, new therapies are needed. In a phase 2, randomized, placebo-controlled, double-blind study (JAHH), once-daily baricitinib (bari) resulted in significant clinical improvement in patients (pts) with active SLE versus PBO. Bari inhibits JAK1 and JAK2 signalling, and in turn may affect STAT1, STAT2, STAT4 pathways. Therefore, bari has the potential to simultaneously impact several pro-inflammatory immune cytokines implicated in the pathogenesis of SLE, including IFN-α, IFN-γ, IL-6, IL-12, and IL-23.Objectives:The objectives of the current study were: 1) to examine baseline serum cytokines in the JAHH phase 2 clinical trial for correlations with clinical or immunologic assessments; 2) to determine if changes in serum cytokine levels were associated with bari treatment.Methods:Pts enrolled in the JAHH phase 2 trial received daily treatment with PBO, bari 2 mg, or bari 4 mg through week 24. Serum samples were collected at baseline (week [wk] 0), wk 12, and wk 24) from SLE pts (n=270) and 50 sex- and age-matched controls. Samples were analyzed for: IL-2, IL-3, IL-5, IL-6, IL-10, IL-17A, IL-21, IL-12/23p40, IL-12p70, GM-CSF, IFN-α and IFN-γ using ultrasensitive quantitative assays. IFN gene signature, autoantibodies, C3 and C4 were measured as previously described [1].Results:At wk 0, serum IL-17A, IL-12/23p40, IL-6, IFN-γ and IFN-α were readily detectable. IL-12/23p40 was detectable in 100% of pts vs. 100% of controls, IFN-γ in 89% of pts vs. 66% of controls, IL-6 in 53% of pts vs. 12% of controls and in IFN-α 41% of pts vs. 2% of controls; detection of serum IL-2, GM-CSF, IL-5, IL-10 and IL-17A was variable (Fig 1). At baseline (wk 0), IL-12/23p40 was positively correlated with SLEDAI and IFN gene signature and negatively correlated with serum C4. IL-6 was positively correlated with joint swelling, joint tenderness, IFN-γ and C3. Serum IFN-α was positively correlated with serum IFN-γ, anti-Sm and anti-RNP, and the IFN gene signature (Fig 2). Treatment with bari 4 mg (Fig 1B) significantly decreased serum IL12/23p40 and IL-6 cytokine levels at wk 12 (p<0.05) but not serum IFN-α or IFN-γ levels (Fig 1B).Figure 1.* p = 0.015; ** p = 0.001; Abbreviations: LLOQ, Lower limit of quantification.Figure 2.Abbreviations: Anti-dsDNA, Anti-double stranded DNA; Anti-RNP, Anti-ribonucleoprotein; CLASI, Cutaneous lupus erythematosus disease area and severity index; SLEDAI, SLE disease activity index.Conclusion:Bari 4 mg treatment was associated with statistically significant decreases of serum IL-12/23p40 and IL-6 at week 12 which continued through week 24. Serum IFN-α or IFN-γ were not reduced with bari treatment. Thus, bari 4 mg simultaneously impacted multiple pro-inflammatory cytokines implicated in the pathogenesis of SLE.

P4450Atherosclerosis in women with systemic lupus erythematosus with and without nephritis

Abstract Background Nephritis in systemic lupus erythematosus (SLE) is a factor contributing to early development of atherosclerosis (AS). Objectives The aim of the study is to determine differences in cardiovascular risk factors and AS in SLE pts with and without lupus nephritis (LN). Methods The study included 162 females, age 35 [26–43] years (median [interquartile range 25–75%])) with SLE (ACR,1997). We divided SLE pts on two groups, comparable in age: the 1st group is the pts with LN (n=84, 52%), the 2nd - without LN (n=78, 48%). We considered traditional factors of cardiovascular disease (CVD): (smoking, family history of CVD, blood pressure, cholesterol (total, HDL, LDL) and triglyceride (TG) levels, body mass index, diabetes mellitus) and SLE-related factors (age at onset, duration, clinical features, SLE Disease Activity Index (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics damage index (SLICC/DI), treatment with steroids); intima-media thickness (IMT) and the 10-year risk for coronary events. Carotid intima-media wall thickness of common carotid arteries was measured by high resolution B-mode ultrasound. The 10-year risk for coronary events was estimated by the Framingham risk equation. Results Median SLE duration was 8,0 [2,3–17,0] years, SLEDAI 2K – 8 [3–16], SLICC/DI score – 2 [0–3], duration of prednisone treatment – 72 [26–141] months. SLE pts from the 1st group had higher prevalence of hypertension (61% vs 36%, p<0,01), systolic blood pressure (130 [110–150] vs 120 [110–130]mm Hg, p<0,01), diastolic blood pressure (80 [70–95] vs 70 [70–80] mm Hg, p<0,05), TG concentration (136 [98–184] vs 100 [61–162] mg/dl, p<0,01), Framingham Risk Score (5 [1–30] vs 1 [1–27]%, p<0,05), SLEDAI-2K (12 [5–19] vs 4 [2–10], p<0,ehz745.08501), SLICC/DI score (2 [0–4] vs 0 [0–2], p<0,01), prednisone therapy duration (95 [26–192] vs 44 [14–98] months, p<0,05), prednisone cumulative dose (34,4 [13,6–82,5] vs 15,7 [6,2–35,2] g, p<0,001), mean IMT (0,73 [0,65–0,83] vs 0,67 [0,61–0,75] mm, p<0,01), than the pts from the 2nd group. There is no difference in CVD frequency in these groups (17% vs 8%, p=0,084). Conclusions SLE patients with and without LN had no difference in frequency of clinical manifestations of AS (CVD), but had a greater value of mean IMT, Framingham Risk Score and a higher incidence of both traditional (hypertension, TG concentration) and SLE-related (disease activity, prednisone therapy) risk factors for AS.

Circulating B Cell Subsets from Untreated Diffuse Large B Cell Lymphoma (DLBCL) Patients Resemble Those of Patients with Autoimmune Disease

IntroductionDiffuse large B cell lymphoma (DLBCL) is a clinically and genetically heterogeneous malignancy that can arise from B cell-mediated autoimmune (AI) diseases such as systemic lupus erythematosus (SLE). Profiling B cell subsets by multicolor flow cytometry can delineate SLE pts from healthy controls and correlates with differences in SLE outcomes (Tipton CM, Nat Immunol 2015). Emerging data suggest that expansions of IgD-CD27- (“double-negative,” DN) memory B cells in SLE are comprised of a novel subset representing pre-plasma cell effector B cells (Sanz MS under review), with at least 15% of DN B cells expressing autoantibodies. Given the etiologic link between autoimmunity and DLBCL, we hypothesized that B cell profiling in DLBCL patients (pts) with and without concomitant AI disease could identify variations in B cell repertoire similar to those observed in SLE patients and reveal links to distinct subtype variations based on biology and etiology.MethodsPts with DLBCL were prospectively identified and consented to participate. All pts were followed longitudinally for clinical data annotation and sample re-collection. Peripheral blood mononuclear cells were isolated from whole blood using density-gradient centrifugation, stained with a 13-color cocktail that included fluorochrome-conjugated mouse monoclonal antibodies to CD3, CD11c, CD19, CD20, CD21, CD24, CD27, CD38, IgD, and Ig light chain kappa and lambda, and then analyzed via flow cytometry with gating analysis using FlowJo. After excluding dead cells, doublets, and non-lymphocytes, we gated on CD19+ B cells and assessed subpopulations based first on expression of IgD and CD27 to distinguish mature-naïve B cells (IgD+CD27-) from switched (IgD-CD27+), unswitched (IgD+CD27+), and DN (IgD-CD27-) memory B cells. Additional cell surface markers (e.g., CD24, CD38) defined other subsets such as antibody-secreting cells and transitional B cells. We examined pre-treatment B cell profile to characterize baseline variations in DLBCL. To examine changes in B cell profile relative to treatment, DLBCL pt samples were evaluated: after completion of standard first-line chemoimmunotherapy; in remission ≥ 1 year from treatment; and at relapse. The Kruskal-Wallis test was used to compare B cell subset distributions between samples.ResultsPeripheral blood was collected from a total of 59 DLBCL pts, with 8 pts contributing samples at >1 time-point. B cell profiling of pre-treatment samples (n=12) revealed two distinct phenotypes according to CD27 and IgD expression: 7 pts' profiles resembled those of healthy controls (42%), and 5 exhibited diminished unswitched memory B cells (<10% of CD19+ cells), similar to SLE pts (Figures 1 and 2). Within the latter group, 4 pts also exhibited DN expansion (>10% of CD19+ cells), a phenotype similar to SLE pts with poor outcomes. Plasmablasts, transitional B cells, switched memory and naïve B cells in untreated DLBCL were not significantly expanded. As expected, CD19+ B cells were uniformly depleted following chemoimmunotherapy, constituting <1% lymphocytes until about 9 months post-treatment. Prior to B cell reconstitution, this small B cell population consisted predominantly of DN cells (Figure 3).ConclusionsIntriguingly, a subset of untreated DLBCL pts exhibit diminished unswitched memory B cells and DN expansion characteristic of SLE pts. It is unclear whether the DN expansion we detected in non-AI-associated DLBCL represents an immune response to tumor or a state of subclinical immune dysregulation that predisposes to DLBCL development, perhaps via chronic antigen stimulation as postulated in AI-associated lymphomas. Longitudinal studies are ongoing to evaluate associations between abnormal B cell profiles, clinical factors, and survival outcomes [Display omitted] DisclosuresFlowers:BeiGene: Research Funding; TG Therapeutics: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Pharmacyclics/ Janssen: Consultancy; Bayer: Consultancy; Acerta: Research Funding; Karyopharm: Consultancy; Genentech/Roche: Consultancy; National Cancer Institute: Research Funding; Celgene: Research Funding; Millennium/Takeda: Research Funding; Spectrum: Consultancy; Genentech/Roche: Research Funding; Janssen Pharmaceutical: Research Funding; V Foundation: Research Funding; OptumRx: Consultancy; Burroughs Wellcome Fund: Research Funding; Pharmacyclics: Research Funding; Abbvie: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; Gilead: Consultancy; Denovo Biopharma: Consultancy.

THU0031 Factors Associated with Fatigue in Systemic Lupus Erythematosus Patients

Backgroundevidence exists that fatigue is a significant problem for systemic lupus erythematosus (SLE) patients (pts). The causes of fatigue aren't enough investigated. SLE activity and depression are confounding fatigue factors.Objectivesto...

AB0554 Expression of Serum B Cell Activating Factor from the Tumour Necrosis Factor Family (BAFF) and A Proliferation-Inducing Ligand (APRIL) in Systemic Lupus Erythematosus: Relationship with Disease Activity

BackgroundThe B lymphocyte stimulator signaling pathway by BAFF and its homologue APRIL has an important role in the selection, maturation and survival of B cells and plays a significant role...

AB0036 Different Regimens of Vitamin D Supplementation Determine an Effect on Phenotype and Function of T Cells in Patients with Systemic Lupus Erythematosus. Results from A Prospective Study

BackgroundIn addition to the classical role on bone metabolism, recent studies highlight that vitamin D (VD) may have an immunomodulatory action on T cells, inhibiting Th-1 and Th-17 response and...

AB0530 Thrombosis Risk Factors in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus With/Without Antiphospholipid Syndrome

BackgroundRheumatoid arthritis (RA), Systemic Lupus Erythematosus (SLE), Antiphospholipid syndrome (APS) are associated with increased mortality and co-morbidity compared with the general population. These patients (pts) may have an increased risk...

AB0393 Comparison of multi-line dot assay and enzyme-linked immunosorbent assay for detection of autoantibody profile in antiphospholipid syndrome

BackgroundDiagnosis of antiphospholipid syndrome (APS) still remains a laboratory challenge due to the great diversity of antiphospholipid antibodies (aPL) and their significance regarding APS classification criteria. Standardized enzyme-linked immunosorbent assay...

THU0186 Cardiac valve abnormalities in systemic lupus erythematosus (SLE) patients detected by transthoracic and transesophageal echocardiography (TTE and TEE)

BackgroundSLE can affect all components of the heart, namely the pericardium, conduction system, myocardium, valves, and coronary arteries. Valvular heart disease is one of the most typical and prognostically significant...

FRI0538 Gender-specific effort-reward imbalance in patients with systemic lupus erythematosus?

BackgroundWorking life factors influence patients’ (life) satisfaction and well being. Effort at work is part of a social contract that reciprocates effort by adequate reward. Components of work-related rewards matter...

FRI0537 Self-reported health status and effort-reward imbalance in patients with rheumatoid arthritis and systemic lupus erythematosus

BackgroundWork environment factors influence patients’ (life) satisfaction and well being. The model of effort-reward imbalance (ERI) was developed to identify health-adverse effects produced by a stressful psychosocial job-related environment. Research...

FRI0281 Cardiac valve abnormalities progression in systemic lupus erythematosus (SLE) patients detected by transthoracic and transesophageal echocardiography (TTE and TEE): 3-year follow-up

BackgroundValvular heart disease is one of the most typical and prognostically significant cardiac lesions in SLE. It is not generally accepted whether valve lesions in SLE have a progressive or...

THU0185 Independent risk factors of endothelial dysfunction (ED) and atherosclerosis (AS) development in patients with systemic lupus erythematosus (SLE)

BackgroundHigh-frequency of traditional risk factors of AS development is well-proven for patients (pts) with SLE. Significance of immunological and inflammatory factors, character of treatment and other factors were also reported....

SAT0230 Atherosclerosis of coronary arteries and coronary heart disease in patients with systemic lupus erythematosus (autopsy and intravital findings)

ObjectivesTo study frequency and character of atherosclerotic damage of coronary arteries (CA) and associated coronary heart disease (CHD) in patients (pts) with systemic lupus erythematosus (SLE); to suggest a rational...

AB0416 Clinical and immunological association with autoantibodies to cellular antigen in a cohort of 532 sle patients from a single center.

Backgroundautoantibodies (autoabs) to cellular antigens can be associated with specific clinical and immunological subsets of Systemic Lupus Erythematosus (SLE).Objectivesto analize the frequencies of different autoabs detected by counterimmunoelectrophoresis (CIE) and...

THU0333 Frequency and Nature of Atherosclerotic Damage of Arteries in Systemic Lupus Erythematosus

Objectivesstudy frequency and nature of atherosclerotic damage of extracranial arteries (ECA), coronary arteries (CA), leg arteries (LA) and associated symptoms in patients (pts) with systemic lupus erythematosus (SLE).MethodsStudy included 100...

AB0867 The coexistence of rheumatic diseases with inflammatory bowel diseases

BackgroundThe association between various rheumatic diseases and inflammatory bowel diseases is suggested by many clinical and experimental observations. Immunological disturbances play a crucial role in the pathogenesis of both rheumatic...