High Systemic Lupus Erythematosus Activity Research Articles

Predictive value of Doppler echocardiography parameters for cardiovascular events in patients with systemic lupus erythematosus.

This study aimed to assess the utility of Doppler echocardiography in evaluating left ventricular diastolic function, and prognosis in patients with systemic lupus erythematosus (SLE). A total of 286 SLE patients were selected along with 100 age- and gender-matched healthy individuals who underwent physical examinations. Clinical baseline characteristics were collected. Various Doppler echocardiographic parameters were measured and analyzed, including left ventricular posterior wall thickness (LVPWT), interventricular septal diameter (IVSD), left ventricular mass (LVM), LVM index (LVMI), and others. Compared to the control group, SLE patients exhibited significantly higher levels of C-reactive protein and lower levels of complement (C) 3 and C4 (p < .001). Doppler echocardiographic parameters showed significant differences between SLE patients and healthy controls, including increased LVPWT, IVSD, LVM, LVMI, peak A, PWI + Tei, E/e', TDI-Tei, and decreased e' and E/A (p < .001). Subgroup analyses indicated more severe ventricular diastolic dysfunction in patients with higher SLE activity and those who experienced cardiovascular events. Correlation analysis revealed positive associations of PWI + Tei, TDI-Tei, and GLS with SLE activity and cardiovascular events (p < .01). Multivariate logistic regression analysis identified LVMI, PWI + Tei, TDI-Tei, and GLS as significant predictors of cardiovascular events (p < .05). Doppler echocardiography is a valuable tool for the early diagnosis of left ventricular diastolic dysfunction in SLE patients. Key echocardiographic parameters, including LVMI, PWI + Tei, TDI-Tei, and GLS, are effective in predicting cardiovascular events, underscoring the importance of comprehensive cardiac function assessments in these patients.

Citrullinated histone H3 in systemic lupus erythematosus and antiphospholipid syndrome (preliminary results)

Citrullinated histone H3 (CitH3) is a specific marker for NETosis; its role in determining the clinical and laboratory manifestations of systemic lupus erythematosus (SLE) remains to be elucidated.Objective: To evaluate the role of CitH3 in the development of clinical and laboratory manifestations in patients with SLE with and without an-tiphospholipid syndrome (APS).Material and methods. The study included 30 patients with SLE and 39 with SLE+APS, including 51 (73.9%) women and 18 (26.1%) men. The median age of the patients was 36 [32; 46.5] years. The control group consisted of 26 healthy individuals.SLE activity was assessed by the SLEDAI-2K index. Patients were divided into two groups: 41 patients with moderate and high SLE activity (SLEDAI-2K ≥6) were included in the first group, and 28 patients with low activity or remission (SLEDAI-2K &lt;6) were included in the second group.CitH3 content in blood serum was determined by enzyme immunoassay using a set of reagents for the assay of CitH3 (BlueGene Biotech, China) according to the manufacturer's instructions.Results and discussion. CitH3 content in blood serum was significantly higher in SLE than in the control group (p=0.048). High blood serum CitH3 content was associated with moderate and high SLE activity (p=0.039). CitH3 concentration was inversely correlated with lymphocyte count but was not related to immunological parameters. Increased CitH3 levels were associated with photosensitivity, while lower levels were associated with a history of serositis. There were no significant differences between blood serum CitH3 levels in patients with SLE and SLE+APS (p=0.39).Conclusion. The concentration of a specific marker for NETosis, CitH3, is increased in patients with SLE, and this increase is associated with moderate and high disease activity.

Mental disorders in patients with systemic lupus erythematosus: association with activity and the course of rheumatic disease

To clarify the relationship between the clinical and psychopathological features of mental disorders, clinical and laboratory manifestations of activity and the nature of the course of systemic lupus erythematosus (SLE). The study included 119 patients - 98 (82.4%) women, mean age 36.5±12.4 years (M±SD) - with a reliable diagnosis of SLE (EULAR/ACR 2019 criteria), 51 (29.5%) of them - with secondary antiphospholipid syndrome - APS (International criteria of 2006). Among patients with SLE a high frequency of anxiety-depressive spectrum disorders (ADSD) and cognitive impairment (CI) was revealed. There was an association of greater severity of depression with high SLE activity index, acute/subacute onset of the disease course according to the classification of V.A. Nasonova, relapsing-remitting and chronic active current disease activity patterns of SLE according to the classification of S. Barr - M. Petri. Anxiety disorders were associated with subacute onset and relapsing-remitting disease activity patterns of SLE and were not associated with SLE activity index. Bipolar disorder was detected more often in patients with chronic SLE. Acute psychosis/delirium was associated with acute onset of SLE. Organic CI was associated with APS, chronic onset and long quiescent disease activity patterns of SLE. The episindrome and schizotypal disorder in patients with SLE are more often caused by concomitant APS. Patients with high SLE activity index should be of particular concern to rheumatologists regarding the diagnosis of depressive disorders. Patients with concomitant APS need timely diagnosis and treatment of CI and episindrome in order to improve the prognosis of the disease and the overall quality of life.

Markers of NETosis in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome.

Neutrophil Extracellular Traps (NETs) have been implicated in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) pathogenesis. The myeloperoxidase-deoxyribonucleic acid (MPO-DNA) complex and nucleosomes are serum markers of NETosis. The aim of this study was to assess these NETosis parameters as markers for SLE and APS diagnosis and their association with clinical features and disease activity. A total of 138 people were included in the cross-sectional study: 30 with SLE without APS, 47 with SLE and APS, 41 patients with primary antiphospholipid syndrome (PAPS), and 20 seemingly healthy individuals. Serum MPO-DNA complex and nucleosome levels were determined via an enzyme-linked immunosorbent assay (ELISA). Informed consent was obtained from all subjects involved in the study. The Ethics Committee of the V.A. Nasonova Research Institute of Rheumatology (Protocol No. 25 dated 23 December 2021) approved the study. In patients with SLE without APS, the levels of the MPO-DNA complex were significantly higher compared to patients with SLE with APS, with PAPS, and healthy controls (p < 0.0001). Among patients with a reliable diagnosis of SLE, 30 had positive values of the MPO-DNA complex, of whom 18 had SLE without APS, and 12 had SLE with APS. Patients with SLE and positive MPO-DNA complex levels were significantly more likely to have high SLE activity (χ2 = 5.25, p = 0.037), lupus glomerulonephritis (χ2 = 6.82, p = 0.009), positive antibodies to dsDNA (χ2 = 4.82, p = 0.036), and hypocomplementemia (χ2 = 6.72, p = 0.01). Elevated MPO-DNA levels were observed in 22 patients with APS: 12 with SLE with APS and 10 with PAPS. There were no significant associations between positive levels of the MPO-DNA complex and clinical and laboratory manifestations of APS. The concentration of nucleosomes was significantly lower in the group of SLE patients (±APS) compared to controls and PAPS (p < 0.0001). In SLE patients, the frequency of low nucleosome levels was associated with high SLE activity (χ2 = 13.4, p < 0.0001), lupus nephritis (χ2 = 4.1, p = 0.043), and arthritis (χ2 = 3.89, p = 0.048). An increase in the specific marker of NETosis, the MPO-DNA complex, was found in the blood serum of SLE patients without APS. Elevated levels of the MPO-DNA complex can be regarded as a promising biomarker of lupus nephritis, disease activity, and immunological disorders in SLE patients. Lower levels of nucleosomes were significantly associated with SLE (±APS). Low nucleosome levels were more common in patients with high SLE activity, lupus nephritis, and arthritis.

The experience of rituximab therapy in patients with juvenile systemic lupus erythematosus: the preliminary results of two-center cohort study

Systemic lupus erythematosus is an immunopathological disease which is characterized by a poor prognosis. Biologics applied in the disease treatment allow reducing the corticosteroid toxicity and controlling the disease.Purpose. To evaluate the efficacy and safety of rituximab therapy in children with systemic lupus erythematosus.Material and methods. The retrospective study included data of 48 patients with systemic lupus erythematosus treated with rituximab. Systemic lupus erythematosus was diagnosed based on the SLICC classification criteria. Patients were assessed at baseline disease status, at the time of rituximab initiation and follow-up. The indications for the rituximab were: lupus nephritis, CNS involvement, and hematological involvement resistant to the standard therapy, and in cases of severe corticosteroid toxicity.Results. During rituximab therapy the significant decrease of the SELENA–SLEDAI activity index was observed. There was a significant decrease of the level of antibodies against dsDNA, normalization of the levels of hemoglobin, ESR, complement C4. The proportion of patients with cytopenia decreased up to their complete absence in patients receiving therapy for three years. The number of patients with active lupus nephritis decreased from 16 at the time of rituximab initiation to 1 after 3 years of therapy. Significant dynamics of proteinuria and hematuria was noted, except for 1 patient. The daily dose of corticosteroids was reduced by 90% from baseline in patients treated for 3 years. Serious adverse events included three deaths in patients with high systemic lupus erythematosus activity with uncontrolled macrophage activation syndrome associated with infections. Various infectious complications, hypogammaglobulinemia, which required replacement therapy with intravenous immunoglobulin, were also recorded.Conclusion. Rituximab can be considered as an option for the treatment of severe forms of systemic lupus erythematosus which are resistant to standard therapy. Further studies are required to evaluate efficacy and safety.

Heterogeneity of Stroke in Patients with Systemic Lupus Erythematosus.

Objective The underlying pathophysiology varies according to stroke subtype. However, stroke heterogeneity among patients with systemic lupus erythematosus (SLE) remains unstudied. We hypothesized that the contribution of SLE to stroke might vary according to its subtype and investigated the associations of SLE and various stroke subtypes. Methods Diagnostic codes and electronic medical records were used to identify 70 patients with SLE who developed acute cerebral infarction or intracerebral hemorrhaging at four tertiary referral hospitals between 2008 and 2018. Intracerebral hemorrhaging was classified as lobar or deep, while cerebral infarction was classified according to the SSS-TOAST criteria. Physician notes were used to identify SLE activity, and their prevalences were compared among stroke subtypes. Outcomes were collected from the patients' medical records. Results The most common stroke subtype in patients with SLE was that of undetermined causes (31%), followed by small artery occlusion (16%), cardioaortic embolism (13%), other causes (11%), lobar hemorrhaging (10%), deep hemorrhaging (10%), and large artery atherosclerosis (9%). Stroke onset occurred during a period of high SLE activity in 21 patients (30%). The proportion of patients with high SLE activity varied according to stroke subtype (p=0.039) and was highest for cerebral infarction with undetermined causes. Stroke recurrence or death was observed in 40% of patients within 5 years after the initial stroke onset. Conclusion The contributions of SLE to stroke varied significantly according to the stroke subtype. Given the unfavorable prognosis, close stroke subtype-specific observation by rheumatologists and stroke specialists is recommended after stroke events.

СИНДРОМ АКТИВАЦИИ МАКРОФАГОВ ПРИ РЕВМАТИЧЕСКИХ ЗАБОЛЕВАНИЯХ У ДЕТЕЙ: РЕТРОСПЕКТИВНОЕ ИССЛЕДОВАНИЕ

Macrophage activation syndrome (MAS) is a rare life-threatening complication of rheumatic diseases (RD) that requires early recognition and adequate immediate treatment. Objective of the study: to identify the features of onset of RD in patients who developed MAS, the clinical and laboratory characteristics of the MAS, possible trigger factors and the timing of development. Materials and methods of research: 57 patients (20 boys and 37 girls) with RD who developed MAS were included in a retrospective continuous non-randomized study: 36 (63%) with systemic juvenile idiopathic arthritis (sJIA), 19 (33%) with Systemic lupus erythematosus (SLE), 1 (2%) – with juvenile dermatomyositis (JDM), one (2%) – with overlapping syndrome. Results: in the structure of patients with sJIA, patients with a history of MAS accounted for 28%, among patients with SLE – 7,6%. The median age at the time of sJIA debut in the study group was 2,6 years [1,5; 5,75], patients with SLE – 11,8 years [8,6; 13,95]. The ratio of boys and girls in the study group was 1:1,85. 70 MAS episodes were recorded: 48 – with sJIA, 20 – with SLE, one episode each for JDM and crossover syndrome. A single episode of MAS at the onset had 22% of patients with sJIA, 47% – with SLE, MAS during the course of the disease – 55% and 47%, repeated episodes of MAS – 25% and 5% of patients, respectively. Clinical manifestations of MAS included fever in 91% of children, hepatomegaly in 54%, pericarditis in 51%, skin lesions in 68%, CNS damage in 44%, lung damage in 33%, hyperferritinemia in 96%, thrombocytopenia – in 79%, increased aminotransferases – in 89%, hypertriglyceridemia – in 53%. Patients with sJIA and MAS had statistically significantly earlier onset (p=0,047), a greater number of systemic manifestations (p=0,012), a typical exanthema (p&lt;0,0001), and a smaller number of active joints (p=0,041). 83% of them had episodes of MAS before the initiation of therapy with biological disease-modifying antirheumatic drugs (bDMARDs). There was no statistically significant relationship between the development of MAS with the use of bDMARDs with a clear positive relationship with the violation of the therapy regimen. 19% of patients with sJIA and MAS had a history of infusion reaction to tocilizumab, 8% later had interstitial lung damage. Patients with SLE and MAS at the onset were statistically significantly more likely to have serositis (p=0,0028), ulcers of the oral mucosa (p&lt;0,0001), neuropsychiatric disorders (p=0,0024), positive Coombs' test (p=0,026). All patients received glucocorticoid therapy; experience with the use of GIBP in the study group was limited. Conclusion: MAS in children develops more often with sJIA; the dominant provoking factor is the activity of the underlying disease. The overwhelming majority of patients developed MAS during the course of the disease, less often at the onset. Patients with a history of MAS with sJIA are characterized by an earlier age of onset, a predominance of systemic manifestations, the need for early administration of bDMARDs therapy, and a tendency to infusion reaction to tocilizumab. Against the background of bDMARDs, a subclinical course of MAS with the absence of fever is possible. The risk of developing MAS along with SLE is higher in patients with onset of serositis, ulcers of the oral mucosa, neuropsychiatric disorders, and a positive Coombs' test. MAS cases were detected with high SLE activity at the onset, violation of the treatment protocol.

Safety and efficacy of 23-valent polysaccharide pneumococcal vaccine in patients with systemic lupus erythematosus

Objective: to study the safety and efficacy of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE).Patients and methods. The study included 75 patients with definite diagnosis of SLE at the age of 19–68 years, 10 (13%) of them had high SLE activity, 18 (24%) – moderate, 42 (56%) – low, in 5 (7%) patients the disease was in remission. PPV-23 was injected subcutaneously in a single dose of 0.5 ml. In 60 patients the follow-up period was ≥12 months, in 15 – from 2 to 6 months. Patients were examined before and 1, 3 and 12 months after immunization.Results and discussion. In 38 (50.7%) patients, standard local vaccination reactions of mild and moderate severity were noted, in 1 (1.3%) – a general reaction of mild severity, in 2 (2.7%) – mild diarrhea during 1 day, in 1 (1.3%) – a hyperergic reaction of the Artyus phenomenon type, the symptoms were relieved within 7 days. During 12 months of follow-up, neither exacerbations of SLE, reliably associated with vaccination, nor new autoimmune phenomena, were detected. After 1 year of observation, the number of responders to vaccination was 58%, non-responders – 42%. The duration and activity of the disease, age over 50 years, glucocorticoid therapy &gt; 10 mg per day, did not significantly affect the vaccine response. There was a decrease in the immune response in patients on biologic DMARDs (bDMARDs) therapy compared to patients without such treatment (43 and 68% of cases, respectively), p=0.058. There was no difference between rituximab and belimumab treated subjects. There was a tendency for the prevalence of vaccination responses among patients, who received bDMARDs &lt;1 year before immunization, as well as among patients in whom this therapy was initiated after the administration of PPV-23. There was a positive trend in decrease of pneumonia, acute and exacerbations of chronic bronchitis episodes and sinusitis.Conclusion. Sufficient immunogenicity, good tolerability and clinical efficacy of PPV-23 in patients with SLE, including those who received combined immunosuppressive therapy, have been shown. The use of bDMARDs reduces the number of patients with a vaccine response. The number of responders to vaccination increases when immunization is carried out before the initiation of therapy with bDMARDs or when this therapy is initiated &lt;1 year before immunization. Further long-term prospective studies in large patient cohorts are required.

Impact of markers of endothelial injury and hypercoagulability on systemic lupus erythematosus

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.

Value of Speckle Tracking Echocardiography for Early Detection of Left Ventricular Dysfunction in Patients with Systemic Lupus Erythematosus.

Background:Cardiac dysfunction due to systemic lupus erythematosus (SLE) may be subclinical, but those patients are at high risk for developing clinical heart failure.Aim:The aim of this study is to assess the role of speckle tracking echocardiography (STE) in the early detection of systolic dysfunction in SLE patients.Patients and Methods:This was a case–control study. Participants were subdivided into two groups: Group 1 included 50 SLE patients and Group 2 included 50 healthy controls. Clinical evaluation, echocardiography, tissue Doppler, and STE were performed.Results:Global longitudinal strain (GLS) was significantly reduced in SLE group (−18.95 ± 2.02 vs. −21.4 ± 2.1, P < 0.001). However, there was no significant difference in left ventricular ejection fraction between both groups (P = 0.801). There was a significant positive correlation between the disease duration and age (r = 0.480, P < 0.001), pulmonary artery systolic pressure (PASP) (r = 0.628, P < 0.001), and GLS (%) (r = 0.417, P = 0.012). There was also a significant positive correlation between the disease activity index and GLS (%) (r = 0.7, P < 0.001) and PASP (r = 0.522, P < 0.001).Conclusion:SLE group had GLS % lower than the control group, and this was statistically significant, denoting early systolic dysfunction. Longer duration and high SLE activity index significantly affect GLS. GLS is an excellent noninvasive tool for early detection of subclinical left ventricular systolic dysfunction in SLE patients.

Efficacy and tolerance of selective and non-selective factor Xa inhibitors in the prevention of thrombosis in kidney disease in patients with systemic lupus erythematosus and antiphospholipid syndrome

The use of factor Xa inhibitors is justified in the therapy of thrombosis in antiphospholipid syndrome (APS) and active lupus nephritis (LN). To monitor the efficacy and safety of these drugs, plasma anti-Xa (aXa) activity is determined. Objective : to assess the aXa activity of selective and non-selective factor Xa inhibitors in patients with systemic lupus erythematosus (SLE) and APS depending on how they affect the kidneys. Patients and methods. Clinical and laboratory findings were prospectively analyzed in SLE and APS patients who long received low molecular weight heparins (LMWHs) and selective Xa inhibitors, such as fondaparinux and rivaroxaban. The investigation enrolled 70 patients (54 females and 16 males) aged 39 years (range, 31 to 43 years) with SLE (n=15 (21%)), primary APS (PAPS) (n=10 (14%)), and SLE + APS (n=45 (65%)). Results . Kidney disease was diagnosed in 33 (47%) of the 70 patients. LN was detected in 15 (25%) of the 60 patients: 10 and 5 patients with SLE and SLE + APS, respectively. APS nephropathy (APSN) was manifested by elevated creatinine and urea levels with normal urine sediment and no history of glomerulonephritis and was observed in 18 (33%) of the 55 patients: in 16 with SLE + APS and 2 with PAPS. The therapeutic aXa range of 0.1—1.5 IU/ml was found in 43 (61%) of the 70 patients, low and high aXa activities were seen in 14 (20%) and 13 (19%) patients, respectively. In patients with APSN, the creatinine clearance (CC) depended on aXa levels: the highest CC was noted in patients with aXa >1.5 IU/mL, the lowest CC was in those with aXa <0.9 IU/ mL (p=0.046). The levels of aXa above the therapeutic range were more common in patients taking fondaparinux (9 (31%) out of the 29 patients) than in those using nadroparin (2 (7%) out of the 29 patients) (odds ratio (OR) 1.92; 95% confidence interval (CI), 1.25—2.97; p=0.04). In the fondaparinux group, high aXa was more frequently observed in patients with high SLE activity (7 (47%) out of the 15 patients) than in those with moderate or mild SLE activity (none out of the 7 patients) (OR 1.88; 95% CI, 1.17—3.01; p=0.037) and was unassociated with LN. The highest aXa level with no signs of hemorrhage was 2.08 IU/mL. Conclusion. The level of aXa is a qualitative laboratory marker for the efficacy and safety of LMWHs and fondaparinux. In patients with APS, the enhanced aXa activity of LMWHs and fondaparinux was associated with elevated CC and was not accompanied by hemorrhage. Fondaparinux is an effective and safe anticoagulant for the treatment and prevention of thrombosis in SLE and APS. The therapeutic window for aXa should be extended in these patients.

Pharmacoeconomic analysis of using belimumab for the treatment of systemic lupus erythematosus

The aim is to study the clinical and economic aspects of using belimumab for the treatment of systemic lupus erythematosus (SLe) in patients with high SLe activity, the presence of anti-DNA, a low level of complement in the blood plasma and minimal lupus organ damage at the early stage.Materials and methods. The Markov model of SLe is used. The initial probabilities of the Markov transitions are obtained from analysis of published clinical and observational studies. The prices of the relevant drugs were obtained from the VeD price registry. Medical and nonmedical expenses are calculated on the basis of the current standards for financial costs and coefficients, as well as payments for temporary and permanent disability. Indirect costs are calculated using the method of human capital.Results. It has been found that using belimumab leads to a decrease in costs (both direct and indirect), as well as an increase in patient survival. The total costs for belimumab vs standard therapy approximated 8.84 million rubles vs 17.72 million rubles (of which 4.05 million rubles vs 5.58 million rubles were direct costs, and 2.57 million rubles vs 2.88 million rubles were indirect medical costs) on average per patient in the belimumab group vs standard therapy group, respectively.Conclusion. The use of belimumab in the target population of patients is pharmacoeconomically justified and expedient because it leads to increased treatment efficiency and reduction of direct and indirect costs.

INVESTIGATION OF IMMUNOGENICITY AND SAFETY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Objective: to investigate the safety and immunogenicity of 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE). Subjects and methods. The investigation enrolled 30 patients with a reliable diagnosis of SLE; of them there were 27 women and 3 men at the age of 19 to 62 years. The disease duration ranged from 9 months to 20 years. At the time of inclusion in the investigation, the disease activity was high in 2 patients, moderate in 3, and low in 20; five patients were in remission. During a year before vaccination, pneumonia was detected in 5 (16.7%) of the 30 patients; there were a total of 18 episodes of various respiratory and ENT infections. The patients were examined at baseline and at 1, 3 and 12 months after vaccination. Standard clinical and laboratory studies and a detailed blood immunological analysis were carried out at visits. The levels of IgG antibodies to capsular polysaccharide pneumococcus were determined during each visit. Twenty-nine patients received glucocorticoids (GCs) at a dose of 5–30 mg/day; 24 – hydroxychloroquine; 14 – cytostatics (CS); 10 – biological agents (BAs) (5 – rituximab, 5 – belimumab). A single dose of 0.5 ml of PPV-23 (Pneumo 23, Aventis) was subcutaneously injected into the upper outer arm. Vaccination was done during the ongoing therapy with GC/CS and belimumab, as well as at least 1 month before the first (next) administration and/or 4.5–5 months after the last rituximab infusion. Results and discussion. 60% of patients were observed to have mild and moderate standard local vaccine reactions; 1 (3.3%) patient had a local hyperergic reaction eliminated within 7 days of the local application of antihistamines and GCs. During the follow-up, there was no SLE exacerbation significantly associated with the vaccination performed. No new autoimmune phenomena were found in any of the cases. A year after vaccination, a significant (2-fold or more) increase in anti-pneumococcal antibody levels remained in 19 (63.3%) patients (respondents); 36.7% of patients were nonrespondents. Among the patients who received a BA, the non-responders were significantly more than among those who did not take the drug (7 (70%) and 4 (20%), respectively) (p = 0.01). When treated with rituximab and belimumab, the number of non-respondents was comparable (4 and 3, respectively). The immunogenicity of PPV-23 was independent of the degree of SLE activity: the vaccine response was absent in 1 out of the 5 patients with high (n = 2) and medium (n = 3) SLE activities, as well as in 10 out of the 25 patients with low disease activity and remission. There was no development of considerable adverse reactions after vaccination in patients with high and medium SLE activity. The overall clinical efficiency of vaccination was 93.3%. Conclusion. Thus, PPV-23 shows a good tolerability and a sufficient immunogenicity in patients with SLE. There is a need for further investigations conducted in large samples of patients during long-term follow-ups in order to more fully evaluate the clinical efficacy, tolerability, and immunogenicity of PPV-23.

Gastrointestinal system involvement in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem disorder which can affect the gastrointestinal (GI) system. Although GI symptoms can manifest in 50% of patients with SLE, these have barely been reviewed due to difficulty in identifying different causes. This study aims to clarify clinical characteristics, diagnosis and treatment of the four major SLE-related GI system complications: protein-losing enteropathy (PLE), intestinal pseudo-obstruction (IPO), hepatic involvement and pancreatitis. It is a systematic review using MEDLINE and EMBASE databases and the major search terms were SLE, PLE, IPO, hepatitis and pancreatitis. A total of 125 articles were chosen for our study. SLE-related PLE was characterized by edema and hypoalbuminemia, with Technetium 99m labeled human albumin scintigraphy (99mTc HAS) and alpha-1-antitrypsin fecal clearance test commonly used as diagnostic test. The most common site of protein leakage was the small intestine and the least common site was the stomach. More than half of SLE-related IPO patients had ureterohydronephrosis, and sometimes they manifested as interstitial cystitis and hepatobiliary dilatation. Lupus hepatitis and SLE accompanied by autoimmune hepatitis (SLE-AIH overlap) shared similar clinical manifestations but had different autoantibodies and histopathological features, and positive anti-ribosome P antibody highly indicated the diagnosis of lupus hepatitis. Lupus pancreatitis was usually accompanied by high SLE activity with a relatively high mortality rate. Early diagnosis and timely intervention were crucial, and administration of corticosteroids and immunosuppressants was effective for most of the patients.

Factors associated with increased white matter hyperintense lesion (WMHI) load in patients with systemic lupus erythematosus (SLE).

Introduction White matter hyperintense (WMHI) lesions are the most common finding in magnetic resonance imaging (MRI) of the brain in patients with systemic lupus erythematosus (SLE). Objective The objective of this article is to determine the clinical factors associated with an increase in WMHI lesion load among SLE patients. Method A total of 83 SLE patients with MRI of the brain from National University of Malaysia Medical Centre were included. The WMHI lesion load was determined using the Scheltens score and Fazekas scale, and their distribution was divided into the deep white matter (DWMHI) and periventricular (PVH) regions. The clinical correlates of WMHI lesions were initially determined using univariate analyses and subsequently multivariable regression analyses were performed to determine the independent factors of increased WMHI lesion load. Results MRI of the brain of 46 patients who had WMHI lesions were compared with 37 patients with normal MRI. We found significant association between the presence of WMHI lesions and age, presence of cerebral infarcts, positive antiphospholipid antibody (aPL), active disease, neuropsychiatric lupus (NPSLE) and disease damage. Age, SLEDAI scores, cerebral infarcts and disease damage were significantly associated with higher DWMHI and PVH Scheltens scores. Meanwhile, patients with active lupus nephritis (LN), lower serum albumin and more severe proteinuria were associated with larger Fazekas WMHI lesions. Multivariable regression analysis revealed that the independent factors associated with presence of WMHI lesions were positive aPL and SLEDAI scores ( p < 0.05). Higher WMHI Scheltens scores in both DWMHI and PVH were associated with presence of cerebral infarct but higher PVH lesion load was significantly associated with active SLE disease. Conclusion Presence of WMHI lesions in SLE was significantly associated with cerebral infarcts, aPL and high general SLE activity, suggesting both inflammation and ischaemia as the underlying pathology of these lesions.

THE TIME COURSE OF CHANGES IN B LYMPHOCYTE SUBPOPULATIONS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS DURING THERAPY WITH BIOLOGICAL AGENTS

Objective: to study the baseline level and time course of changes in peripheral blood B cell subpopulations in patients with systemic lupus erythematosus (SLE) versus the clinical manifestations of the disease during therapy with rituximab (RTM) and belimumab (BLM). Subjects and methods. 49 patients with a documented diagnosis of SLE and high and moderate SLEDAI-2K values were divided into three groups: 1) 40 patients received RTM, 2) 5 patients took BLM; 3) 4 patients had combination therapy (dual anti-B-cell therapy) with RTM + BLM. Peripheral blood B lymphocyte subpopulations were measured by multicolor flow cytometry using a panel of monoclonal antibodies against surface membrane markers of B lymphocytes; the patients underwent clinical immunological examination before therapy with biological agents and every 3 months during a year. Results and discussion. Patients with high SLE activity (SLEDAI-2K 18±5) and involvement of vital organs had generally higher levels of double negative memory cells (r = 0.52; p < 0.001) with relatively low counts of naive B cells (r=-0.54; p < 0.0007) than those without severe organ pathology (SLEDAI-2K 8±2). RTM therapy at 3 month of follow-up resulted in a noticeable decrease in the number of naive and double negative memory B cells and to a lesser extent in that of non-switched and switched memory B cell. A rapid recovery of the count of memory B cells and plasmablasts after a RTM cycle at 6 months after therapy initiation should be evaluated as a predictor of early exacerbation of SLE. There was a reduction in the clinical and laboratory signs of SLE activity, as well as inhibition of naive B cells, plasma cells, and plasmablasts in all the 5 patients receiving BLM at various stages of follow-up. Dual anti-B cell therapy most effectively reduced disease activity at 3 months, prolonged the achieved remission, contributed to the achievement and maintenance of a low B lymphocyte level at later stages of control, to the further decline in the number of plasmablasts and plasma cells, and prevented the synthesis of autoantibodies. Conclusion. Assessment of the time course of changes in peripheral blood B lymphocyte subpopulations provides new opportunities to identify impaired function and regulation of cellular immunity in patients with SLE, it may be a useful diagnostic parameter to monitor an autoimmune disease and a valuable tool to assess and predict a response.

Relationship Between Clinical and Immunological Features with Magnetic Resonance Imaging Abnormalities in Female Patients with Neuropsychiatric Systemic Lupus Erythematosus.

Background:Conventional magnetic resonance imaging (MRI) is the preferred neuroimaging method in the evaluation of neuropsychiatric systemic lupus erythematosus (NPSLE). The purpose of this study was to investigate the association between clinical and immunological features with MRI abnormalities in female patients with NPSLE, to screen for the value of conventional MRI in NPSLE.Methods:A total of 59 female NPSLE patients with conventional MRI examinations were enrolled in this retrospective study. All patients were classified into different groups according to MRI abnormalities. Both clinical and immunological features were compared between MRI abnormal and normal groups. One-way analysis of variance was used to compare the systemic lupus erythematosus disease activity index (SLEDAI) score for MRI abnormalities. Multivariate logistic regression analysis investigated the correlation between immunological features, neuropsychiatric manifestations, and MRI abnormalities.Results:Thirty-six NPSLE patients (61%) showed a variety of MRI abnormalities. There were statistically significant differences in SLEDAI scores (P < 0.001), incidence of neurologic disorders (P = 0.001), levels of 24-h proteinuria (P = 0.001) and immunoglobulin M (P = 0.004), and incidence of acute confusional state (P = 0.002), cerebrovascular disease (P = 0.004), and seizure disorder (P = 0.028) between MRI abnormal and normal groups. In the MRI abnormal group, SLEDAI scores for cerebral atrophy (CA), cortex involvement, and restricted diffusion (RD) were much higher than in the MRI normal group (P < 0.001, P = 0.002, P = 0.038, respectively). Statistically significant positive correlations between seizure disorder and cortex involvement (odds ratio [OR] = 14.90; 95% confidence interval [CI], 1.50–151.70; P = 0.023) and cerebrovascular disease and infratentorial involvement (OR = 10.00; 95% CI, 1.70–60.00; P = 0.012) were found.Conclusions:MRI abnormalities in NPSLE, especially CA, cortex involvement, and RD might be markers of high systemic lupus erythematosus activity. Some MRI abnormalities might correspond to neuropsychiatric manifestations and might be helpful in understanding the pathophysiology of NPSLE.

RESULTS OF AN OBSERVATIONAL PROSPECTIVE STUDY OF THE EFFICACY AND SAFETY OF BELIMUMAB (BENLYSTA®) IN SYSTEMIC LUPUS ERYTHEMATOSUS IN REAL CLINICAL PRACTICE

Therapy for systemic lupus erythematosus (SLE) remains challenging. The long-term use of glucocorticoids (GC) and cytostatics considerably improves life expectancy, but at the same time favors the development of irreversible organ damages. To evaluate the efficacy of belimumab (BLM), a biological agent, that blocks B-lymphocyte-stimulating factor registered for the treatment of active SLE, is an important task of the practice of rheumatology. Objective: to evaluate the efficacy and safety of BLM in patients with high and moderate SLE activity. Subjects and methods. The investigation enrolled 16 patients with a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) score of 6 to 19, who were positive for antinuclear factor (100%) and had low complement levels and high anti-native DNA antibodies (81%). BLM was used as monthly intravenous infusions at a dose of 10 mg/kg. The efficiency and safety of the therapy were evaluated monthly and 1 year after the initiation of treatment with BLM; SLE activity was estimated using SLEDAI-2K; a physician’s global assessment of disease activity on a visual analogue scale (VAS); anti-DNA antibody level changes, complement levels, a GC dose, damage index, and adverse events were determined. Results and discussion. BLM therapy proved to be effective in 62% of cases at 1 year after therapy initiation. At 1 month, SLE activity significantly decreased with SLEDAI-2K score diminishment from 9.31±3.21 to 6.25±2.80 in the entire group (p < 0.04). Over a month, the physician’s global assessment of disease activity significantly reduced from 19.25±6.60 to 13.68±3.97 mm (р<0.01) and reached minimum (8.28±6.87 mm) by 10 months of therapy. There was a significant decrease in anti-DNA antibodies and an increase in complement C4 level at 5 and 3 months of therapy, respectively. Six of the 10 patients who had received a complete cycle of BLM therapy achieved remission at 12 months. The dose of GC was significantly reduced at 6 months of therapy. Adverse events were rare. BLM was discontinued because of its inadequate efficacy in 4 patients. Conclusion. Twelve-month therapy with BLM is effective in patients with high and moderate SLE activity according to SLEDAI-2K and with high immunological activity. The use of BLM in SLE contributes to a GC dose reduction and fails to cause serious adverse events.

Clinical manifestations, courses, and outcomes of systemic lupus erythematosus in the dwellers of Kyrgyzstan

Objective: to investigate the clinical manifestations, courses, outcomes, and unfourable predictors of systemic lupus erythematosus (SLE) in the dwellers of Kyrgyzstan. Subjects and methods. The investigators carried out a retrospective analysis of 107 patients with SLE, who fulfilled the respective 1982 American College of Rheumatology (ACR) criteria and had been examined and treated at the Clinic of the National Center for Cardiology and Therapy in 2001 to 2011, and a prospective follow-up of 75 of them until 2015. During the prospective follow-up study, 29 of the 75 patients died on average of 6.38±3.48 years after the first visit to the clinic and 46 were alive at the completion of the investigation. The patients’ baseline status was retrospectively analyzed. Disease activity was assessed using SLEDAI-2K. The outcome of SLE was determined as the number of exacerbations by the SLE flare index (SFI): moderate or severe, the occurrence of a complete or drug-induced remission, the development of irreversible organ damages by the Systemic Lupus International Collaborating Clinics/ACR damage index (SLICC/ACR DI) or death. Results and discussion. The prospective follow-up study showed that among the 75 patients, only one achieved a complete clinical and immunological remission and 12 had drug-induced remission. All patients with significantly lower disease activity were observed to have a statistically significant DI increase by one or more scores (p < 0.05). Various irreversible organ damages were detected in 48 (64%) patients; these were found in the survivors 3.5 [2.0; 5.0] years after their first visit and in the deceased patients 1.5 [1.0; 3.0] years prior to death. The main causes of death were renal and pulmonary complications in 10 (34.5%) and 7 (24.1%) patients, respectively. Respiratory infections as severe pneumonias with progressive respiratory failure result in a fatal outcome in 5 (17.2%) cases. The independent risk factors for death were acute course (β = 0.18; p = 0.04), long disease duration out of remission (β = 0.51; p = 0.001), and SLICC/ACR DI progression (β = 0.32; p = 0.0004). High SLE activity failed to affect mortality rates (β = 0.09; p = 0.02) that showed no significant decrease over time (p = 0.14). Conclusion. The poor predictors in patients with SLE were acute course, long disease duration out of remission, and progression of irreversible organ damages.

Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up

ObjectivesGrowing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between...