Lupus Erythematosus Disease Activity Index Research Articles

Association between depression and pain, functional disability, disease activity and health-related quality of life in patients with systemic lupus erythematosus: a meta-analysis

ObjectiveThe aim of this study was to explore the effect of depression on pain, disease activity, functional disability and health-related quality of life measured by Visual Analogue Scale, Systemic Lupus...

Comparison of mycophenolic acid with cyclophosphamide for the treatment of pediatric lupus nephritis: A retrospective study from a tertiary center hospital in Taiwan.

This study aimed to compare the efficacy of mycophenolic acid (MPA) and cyclophosphamide (CYC) for treating pediatric lupus nephritis (pLN). Data on patients with pLN class III, IV, and V, diagnosed by renal biopsy, were collected from the Databank of Kaohsiung Veterans General Hospital between February 2005 and December 2020. The study included 31 pLN patients. Of these, 15 received MPA (MPA group) and 16 received CYC (CYC group). Systemic lupus erythematosus disease activity index score, laboratory findings, complete remission (CR), and partial remission (PR) were assessed at 6, 12, and 24 months. In the MPA group, CR occurred in 7/15 (47%) patients at month 6 and in 11/15 (73%) at months 12 and 24. In the CYC group, CR was reached in 5/16 (31%) patients at month 6, in 8/16 (50%) at month 12, and in 9/16 (56%) at month 24. PR was seen in 3/15 (20%) patients in the MPA group and in 3/16 (19%) in the CYC group at month 24. The cumulative probability of CR and PR showed no statistically significant difference between the two groups. However, the estimated glomerular filtration rate (eGFR) improved significantly in the MPA group at months 6, 12 and 24 compared to that in the CYC group (p<0.05). The efficacy of MPA is similar to that of CYC for pLN treatment, with MPA providing a significant improvement in eGFR after pLN induction therapy at months 6,12 and 24.

Development and validation of a prognostic nomogram for the renal relapse of lupus nephritis

ObjectivesThis study aims to assess the risk of relapse after complete remission (CR) and partial remission (PR), and to develop a prognostic nomogram predicting the probability in lupus nephritis (LN) patients. MethodsData from patients with LN who had been in remission were collected as a training cohort. The prognostic factors were analyzed using the univariable and multivariable Cox model for the training group. A nomogram was then developed using significant predictors in multivariable analysis. Both discrimination and calibration were assessed by bootstrapping with 100 resamples. ResultsA total of 247 participants were enrolled, including 108 in the relapse group and 139 in the no relapse group. In multivariate Cox analysis, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), erythrocyte sedimentation rate (ESR), complement 1q (C1q), and antiphospholipid (aPL), anti-Sm antibody were found to be significant for predicting relapse rates. The prognostic nomogram including the aforementioned factors effectively predicted 1- and 3-year probability of flare-free. Moreover, a favorable consistency between the predicted and actual survival probabilities was demonstrated using calibration curves. ConclusionsHigh SLEDAI, ESR, and positive aPL, anti-Sm antibody are potential risk factors for LN flare, while high C1q can reduce its recurrence. The visualized model we established can help predict the relapse risk of LN and aid clinical decision-making for individual patients.

Impact of low disease activity, remission, and complete remission on flares following tapering of corticosteroids and immunosuppressive therapy in patients with systemic lupus erythematous: a multinational cohort study.

Targets of treatment for systemic lupus erythematosus (SLE) include the Lupus Low Disease Activity State (LLDAS), remission, and complete remission. Whether treatment can be tapered after attaining these targets and whether tapering is safer in patients in complete remission compared with LLDAS are unknown. We aimed to assess the odds of disease flares after treatment tapering in stable disease, versus continuing the same therapy. We also aimed to examine whether tapering in complete remission resulted in fewer flares or longer time to flare compared with tapering in LLDAS or remission. This multinational cohort study was conducted at 25 sites across 13 Asia-Pacific countries. We included adult patients aged 18 years or older with stable SLE who were receiving routine clinical care, had two or more visits and had attained stable disease at one or more visits. We categorised stable disease into: LLDAS (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] score ≤4, Physician Global Assessment [PGA] ≤1, and prednisolone ≤7·5 mg/day); Definitions of Remission in SLE (DORIS) remission (clinical SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day); or complete remission on therapy (SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day). Stable disease categories were mutually exclusive. Tapering was defined as any decrease in dose of corticosteroids or immunosuppressive therapy (mycophenolate mofetil, calcineurin inhibitors, azathioprine, leflunomide, or methotrexate). Using multivariable generalised estimating equations, we compared flares (SELENA-SLEDAI Flare Index) at the subsequent visit after drug tapering. We used generalised estimating equations and Cox proportional hazard models to compare tapering attempts that had begun in LLDAS, remission, and complete remission. Between May 1, 2013, and Dec 31, 2020, 4106 patients were recruited to the cohort, 3002 (73·1%) of whom were included in our analysis. 2769 (92·2%) participants were female, 233 (7·8%) were male, and 2636 (88·1%) of 2993 with ethnicity data available were Asian. The median age was 39·5 years (IQR 29·0-50·0). There were 14 808 patient visits for patients in LLDAS, or remission or complete remission, of which 13 140 (88·7%) entered the final multivariable model after excluding missing data. Among the 9863 visits at which patients continued the same therapy, 1121 (11·4%) flared at the next visit, of which 221 (19·7%) were severe flares. Of the 3277 visits at which a patient received a tapering of therapy, 557 (17·0%) flared at the next visit, of which 120 (21·5%) were severe flares. Tapering was associated with higher odds of flare compared with continuing the same therapy (odds ratio [OR] 1·24 [95% CI 1·10-1·39]; p=0·0005). Of 2095 continuous tapering attempts, 860 (41·1%) were initiated in LLDAS, 596 (28·4%) in remission, and 639 (30·5%) in complete remission. Tapering initiated in LLDAS (OR 1·37 [95% CI 1·03-1·81]; p=0·029) or remission (1·45 [1·08-1·94]; p=0·013) had higher odds of flare in 1 year compared with complete remission. Tapering in LLDAS (hazard ratio 1·24 [95% CI 1·04-1·48]; p=0·016) or remission (1·30 [1·08-1·56]; p=0·0054) had a significantly shorter time to first flare than tapering initiated in complete remission. Attaining sustained LLDAS, remission, or complete remission for at least 6 months just before the time of taper was associated with lower odds of flare at next visit, flares in 1 year, and longer time to flare. Tapering of corticosteroids or immunosuppressive therapy in patients with stable SLE was associated with excess flares. Our findings suggest that drug tapering should be carefully considered, weighing the risks and benefits, and is best exercised in complete (clinical and serological) remission and after maintaining stable disease for at least 6 months. AstraZeneca, BMS, Eli Lily, Janssen, Merck Serono, GSK, and UCB.

Downregulation of circETS1 disrupts Th17/Treg homeostasis by inhibiting FOXP3 transcription: A new potential biomarker in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with an imbalance of T helper 17 (Th17) to regulatory T cells (Tregs). However, the underlying mechanism remains unclear. Increasing evidence suggests that circular RNAs play a crucial role in SLE. Although circETS1 was discovered 30years ago, detailed exploration of its functions remains limited. In this study, we measured the expression levels of circETS1 in peripheral blood mononuclear cells (PBMCs) and CD4+ T cells of patients with SLE by quantitative polymerase chain reaction. The impact of circETS1 expression on the Th17/Treg balance and underlying mechanism were evaluated using double-luciferase reporter, gain-/loss-of-function, and rescue assays. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic value of circETS1. Both circETS1 and FOXP3 expression were downregulated in the PBMCs and CD4+ T cells of patients with SLE (n = 28) compared with those in the cells of healthy controls (n = 20). Mechanistically, we found that circETS1 can bind directly to the microRNA miR-1205, acting as a sponge to upregulate the transcription of FOXP3, thereby maintaining the Th17/Treg balance. Notably, ROC analysis showed that the expression level of circETS1 in PBMCs had an area under the curve of 0.873 (95% confidence interval: 0.771-0.976; p < .001) for diagnosing SLE, with a sensitivity of 80.00% and a specificity of 89.29%. Finally, we found negative correlations between the level of circETS1 in PBMCs and disease severity (according to the Systemic Lupus Erythematosus Disease Activity Index) in patients with SLE (r = -0.7712, 95% CI: -0.8910 to -0.5509; p < .001). The imbalance in Th17/Treg cells in SLE may be attributed, in part, to the circETS1/miR-1205/FOXP3 pathway. CircETS1 has potential to serve as a valuable biomarker for the diagnosis and evaluation of SLE.

Clinical disease activity index applicability in lupus arthropathy: Unraveling underdiagnosed joint activity.

Lupus arthropathy (LA) ranges from arthralgia and non-deforming arthritis to severe forms such as Jaccoud-type deformities and mutilating arthritis. Considering the evolving concept of LA, measuring arthritis activity in lupus patients may require a more practical and sensitive tool other than the classical composite scores. In this cross-sectional study, we evaluated the articular pattern of a sample of SLE patients which were divided into those that scored in articular domain on Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and those with activity arthritis using the Clinical Disease Activity Index (CDAI). After all, we analyzed the association between CDAI and arthritis by SLEDAI-2K as well as its association with the presence or not of Jaccoud-type arthropathy (JA). A total of 127 patients with SLE were evaluated. According to SLEDAI-2K, 17 (13.4%) patients have scored in its joint criteria and 32 patients (25.19%) were considered to have some articular activity by CDAI. A total of 16 patients (50%) who scored some activity on CDAI did not score in articular domain of SLEDAI-2K. Also, the presence of Jaccoud-type arthropathy was significantly associated with arthritis activity according to the CDAI score (p = .014) but not with SLEDAI-2K joint criteria (p = .524). The CDAI was not directly associated with the presence of arthritis by the joint criteria of SLEDAI-2K and the presence of JA was significantly associated with the CDAI but not with arthritis at SLEDAI-2K.

A single-center model for implementation of SLEDAI documentation adherence in childhood-onset systemic lupus erythematosus (cSLE).

Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease with variable disease expression but noted association with significant disease-related damage, morbidity, and mortality. The European Alliance of Associations for Rheumatology (EULAR) recommends routine monitoring of SLE through validated disease activity and chronicity indices, including the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Despite this, physician adherence with SLEDAI documentation remains elusive at various academic institutions. The aim of our study was to determine baseline SLEDAI documentation rates at our center and assess the change in adherence in SLEDAI documentation rate with electronic clinical decision support (CDS) reminders facilitated through the electronic medical record (EMR) over a 2-year period. All SLE encounters over a 24-month period at a pediatric academic center were reviewed in order to obtain baseline SLEDAI documentation percentages. Physicians subsequently received monthly email reminders, initiated at month 4 of project initiation, with subsequent CDS reminder 13months after project initiation prompted by anti-dsDNA lab result. Chart review was repeated continuously for each provider, and SLEDAI documentation rates were emailed to each provider monthly. Physicians completed a post-intervention survey regarding barriers to SLEDAI documentation at the end of the study. A total of 1980 SLE encounters were reviewed for this study. Baseline SLEDAI documentation rates were 10%. Following the introduction of monthly emails reminding physicians to document SLEDAI, rates increased to 55%. After the initiation of electronic in-basket reminders prompted by lab results, rates increased to 60%. Noted barriers to documentation were cited to be forgetfulness (67%) and lack of time (33%). Our study demonstrates that monthly email reminders as well as EMR-mediated electronic in-basket reminders increased SLEDAI documentation rates at an academic center. Noted barriers to documentation were reported to be forgetfulness (67%) and lack of time (33%).

Analysis of Factors Influencing Whole Blood Hydroxychloroquine Concentration in Patients with Systemic Lupus Erythematosus in China.

The aim of this study was to determine the factors associated with the concentrations of hydroxychloroquine (HCQ) and its major metabolite, desethylhydroxychloroquine (DHCQ), in patients with systemic lupus erythematosus (SLE). Patients with SLE taking oral HCQ for at least 3months were recruited from the Department of Rheumatology and Immunology of Nanjing Drum Tower Hospital. Clinical characteristics and laboratory values were examined. The concentrations of HCQ and DHCQ were measured by high-performance liquid chromatography, and the effects of various factors on the concentrations were investigated. A total of 272 patients were included in this study. The average concentration of HCQ was 690.90ng/ml and the average concentration of DHCQ was 431.84ng/ml. Multivariate analysis indicated that gender (P = 0.015), age (year) (P < 0.001), weight (kg) (P = 0.013), duration of HCQ use (month) (P < 0.001), systemic lupus erythematosus disease activity index (SLEDAI) (P < 0.001), platelet count (× 109/l) (P < 0.001), immunoglobulin G levels (g/l) (P = 0.014) were associated with low HCQ concentrations. Gender (P = 0.006), duration of HCQ use (month) (P < 0.001), SLEDAI (P = 0.007), and platelet count (× 109/l) (P < 0.001) were associated with low DHCQ concentrations. Patients with SLE require long-term administration of HCQ, but blood levels vary widely between individuals. Studying the factors influencing the blood HCQ and DHCQ concentrations and optimizing the dose according to individual characteristics might help to improve the efficacy of HCQ. ChiCTR2300070628.

Clinicopathological Characteristics and Prognosis of Lupus Nephritis Patients with Acute Kidney Injury

Introduction: Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for chronic kidney failure. Here, we aimed to assess the characteristics and prognosis of LN patients with AKI. Methods: AKI and AKI severity stages in LN patients were defined by the Kidney Disease Improving Global Outcomes (KDIGO) classification. Long-term renal outcomes and patient mortality between different stages of AKI were compared by Cox regression analysis. Results: Of 1272 LN patients, 225 (17.69%) had AKI and 72 (5.66%) were AKI stage 3. Compared with the non-AKI group, the proportion of male patients was significantly higher in the AKI group (p = 0.002). In addition, there were markedly higher proportions of hematologic system damage, more severe renal manifestations, and higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores in the AKI group than in the non-AKI group. The active and chronic lesions in renal biopsy were significantly higher in LN patients with AKI than those without AKI. During a median follow-up of 53 months, Kaplan-Meier curve showed that LN patients with AKI stage 3 had significantly poorer long-term renal outcomes (p = 0.002) and patient survival (p < 0.001) than those without AKI. Furthermore, AKI stage 3, but not stage 1 or 2 was significantly associated with adverse renal outcomes (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.01–6.28, p = 0.048) and all-cause mortality (HR = 2.80, 95% CI: 1.18–6.61, p = 0.019) in LN patients. In patients with AKI, increased baseline serum creatinine and severe glomerular sclerosis were independent risk factors for worse renal outcomes, while higher blood pressure, increased baseline serum creatinine, and anti-Sjogren’s syndrome A positivity could indicate poor survival. Discussion: LN patients with AKI stage 3, but not stages 1 and 2, have poorer long-term renal outcomes and patient survival. Our study demonstrates the importance of early identification and management of AKI in LN patients.

Low disease activity state associated with fewer incident vertebral fractures in Mestizo women with systemic lupus erythematosus.

Low disease activity state (LDAS) has been linked to a significant reduction in flares and damage accrual in patients with systemic lupus erythematosus (SLE); however, the effect of LDAS on the risk of vertebral fractures (VFs) in subjects with SLE is unknown, considering that low bone mineral density (BMD) and VF are frequent in SLE. to evaluate whether achieving LDAS ≥50% of the observation time prevents new VF and BMD changes in Mestizo women. We carried out a longitudinal, observational, and retrospective study. Mestizo women with SLE were included for a median of an 8-year follow-up. LDAS was described as Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≤4, prednisone ≤7.5mg/day, and stable immunosuppressive therapies. BMD measurements and lateral thoracic and lumbar radiographs for a semiquantitative analysis for VF were assessed at baseline and during the follow-up. Uni- and multivariable interval-censored survival regression models were carried out. We included 110 patients: 35 (31.8%) had new VF. A total of 56 patients (50.1%) achieved LDAS ≥50% of the time during the follow-up and achieved a significantly lesser risk of incident VF (HR = 0.16; 95% CI, 0.06-0.49). After adjusting by age, BMI, menopause, prevalent VF, baseline BMD, cumulative glucocorticoid use, and anti-osteoporotic therapy, LDAS-50 was significantly related to a decrease in the risk of a new VF (HR = 0.39; 95% CI, 0.16-0.98). There was no association between LDAS and BMD measurement changes. When only patients on LDAS but not in remission (n = 43) were evaluated for the risk of incident VF, both uni- and multivariate analyses were significant (HR = 0.12; 95 CI, 0.04-47; p = 0.001, and HR = 0.26; 95% CI, 0.7-0.88; p = 0.03). LDAS ≥50% of the time was significantly associated with a diminished risk of new VF in Mestizo women with SLE, even in patients not in remission. However, LDAS did not help modify BMD changes over time.

Decrease of left ventricular function measured by speckle-tracking echocardiography based on systemic lupus erythematosus severity in children.

Systemic lupus erythematosus in children generally manifests more severely with a more aggressive disease course. Cardiac involvement in systemic lupus erythematosus often does not show specific signs and symptoms, but speckle-tracking echocardiography can detect cardiac dysfunction. This study aimed to determine the differences in left ventricular function as measured by speckle-tracking echocardiography in children with various severity of systemic lupus erythematosus activity. A cross-sectional study of 49 children diagnosed with systemic lupus erythematosus are currently undergoing outpatient or inpatient care at Dr Hasan Sadikin General Hospital, Bandung, from May 2023 to June 2023. Disease activity was assessed by Mexican Version of the Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI) with a score of 2-5 classified as mild activity, 6-9 as moderate, and ≥10 as severe. Each subject underwent conventional echocardiography and speckle-tracking echocardiography with a Philips EPIQ machine performed by a Pediatric Cardiologist Consultant 10 days after inclusion. Fifteen (30.6%) subjects had mild disease activity, and 34 (69.4%) subjects had moderate disease activity. Most subjects (81.96%) were female with an average age of 15 years. The mean ejection fraction and fractional shortening as well as the median E/A ratio in the mild and moderate disease activity groups were not significantly different (65.76 versus 67.38%, 35.73 versus 37.11%, 1.6 versus 1.5%, respectively, p > 0.005). The global longitudinal strain in the moderate activity group was reduced more significantly than in the mild activity group (-16.58 versus -19.65, p = 0.008). Left ventricular function as measured by speckle-tracking echocardiography was lower in children with moderate systemic lupus erythematosus activity than those with mild disease activity.

Serum interferon-alpha predicts in-hospital mortality in patients hospitalised with acute severe lupus

ObjectivesDysregulation of interferon-alpha (IFN-α) is considered central to the immunological abnormalities observed in SLE. Short-term mortality during high disease activity in lupus is up to 30%. Adenovirus vector-introduced IFN-α into...

Biomarkers of Oxidative Stress in Systemic Lupus Erythematosus Patients with Active Nephritis.

Oxidative stress plays an important role in systemic lupus erythematosus (SLE) and especially in lupus nephritis (LN). The aim of this study was to compare redox-related biomarkers between patients with active LN, quiescent SLE (Q-SLE) and healthy controls (HC) and to explore their association with clinical characteristics such as disease activity in patients. We investigated levels of plasma free thiols (R-SH, sulfhydryl groups), levels of soluble receptor for advanced glycation end products (sRAGE) and levels of malondialdehyde (MDA) in SLE patients with active LN (n = 23), patients with quiescent SLE (n = 47) and HC (n = 23). Data of LN patients who previously participated in Dutch lupus nephritis studies and longitudinal samples up to 36 months were analyzed. Thiol levels were lower in active LN at baseline and Q-SLE patients compared to HC. In generalized estimating equation (GEE) modelling, free thiol levels were negatively correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) over time (p < 0.001). sRAGE and MDA were positively correlated with the SLEDAI over time (p = 0.035 and p = 0.016, respectively). These results indicate that oxidative stress levels in LN patients are increased compared to HC and associated with SLE disease activity. Therefore, interventional therapy to restore redox homeostasis may be useful as an adjunctive therapy in the treatment of oxidative damage in SLE.

E32 Intra cranial hypertension in juvenile neurolupus

Abstract Introduction Neurolupus is one of the two key prognostic parameters of lupus. Its manifestation can be central or peripheral, revealing the disease or occurring during the course of evolution. It’s important to not consider all neurological manifestations during SLE as related to lupus, ruling out Central nervous system (CNS) infection and anti-phospholipid syndrome (APS) is primordial. Objectives To share 3 rare observations of neurolupus with intracranial hypertension syndrome and discuss their therapeutic modalities. To highlight the lack of evidence in the treatment of such cases. Method A retrospective analysis of data from medical records. Results We report three observations of Intracranial hypertension syndrome involving three girls, ranging from 9 to 14 years. Clinical symptomatology was dominated by headache, vomiting and visual disturbances. Examination found papillary oedema stage 3 in all the three patients, convergent strabismus in two patients and elevated intracranial pressure measurement in all the three girls ranged from 95 mm to 57 mm of H2O. Brain MRI performed in all three-patients was normal. Data from laboratory tests showed, thrombocytopenia in one patient, pancytopenia in one patient, positive antinuclear antibodies in all patients, positive anti-DNA antibody in one patient, C3, C4 consumption in two patients, positive proteinuria in two patients and positive anti phospholipid antibodies in one patient. All patients had active SLE at the time of admission with a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at least at 17. Symptomatic treatment with carbonic anhydrase inhibitor was initiated, followed by methylprednisolone pulse therapy then oral corticosteroids and hydroxychloroquine in all the three patients. Immunosuppressive therapy with Rituximab 1 g at two-week intervals was administrated in two patients, the third one did not receive any suppressive treatment in addition to corticosteroids due to the favorable outcome. The course was favorable in all patients with regression of clinical symptoms of intracranial hypertension and papillary oedema immediately after cerebro spinal fluid (CSF) subtraction. Discussion and Conclusion Neurolupus presents with heterogeneous symptoms that make its diagnosis difficult. Intracranial hypertension syndrome is a rare manifestation resulting from a disorder of CSF resorption, its pathogenesis is poorly understood with an inflammatory hypothesis based on immune deposits. There are no therapeutic recommendations to date. This isolated syndrome without other neurological signs of severity responds very well to symptomatic treatment with carbonic anhydrase inhibitors and to CSF withdrawal, as was the case in our patients. The use of immunosuppressive therapy (rituximab in our patients) was indicated due to the severity of the clinical picture with severe renal involvement. In addition, other immunosuppressive drugs can be an alternative option therapy. Ethics The study was performed according to the principles of the Declaration of Helsinki.

Characteristics and clustering analysis of peripheral blood lymphocyte subsets in children with systemic lupus erythematosus complicated with clinical infection.

Clinical infection is a common complication in children with systemic lupus erythematosus (SLE). However, few studies have investigated immune alterations in children with SLE complicated with clinical infection. We assessed lymphocyte subsets in children with SLE to explore the possibility of clinical infection. We retrospectively analyzed the proportion of peripheral lymphocyte subsets in 140 children with SLE. Children with SLE were classified into different clusters according to the proportion of peripheral blood lymphocyte subsets: (CD3 + /CD4 + T cell, CD3 + /CD8 + T cell, CD3 + /CD4 + /CD8 + T cell, CD3 + /CD4-/CD8- T cell, CD19 + B cell, and CD3-/CD16 + /CD56 + NK cell). Differences in the proportion of lymphoid subsets, infection rates, and systemic lupus erythematosus disease activity index (SLEDAI) scores were compared between clusters. In addition, we grouped the subjects according to the presence or absence of infection. Proportions of lymphoid subsets, demographic variables, clinical presentation, and other laboratory variables were compared between the infected and uninfected groups. Finally, the diagnostic ability of lymphocyte subset ratios to distinguish secondary infection in children with SLE was predicted using an ROC curve. Cluster C2 had a higher proportion of B cells than Cluster C1, while Cluster C1 had a lower proportion of NK cells, CD3 + T cells, CD3 + /CD4 + T cells, CD3 + /CD8 + T cells, and CD3 + /CD4-/CD8- T cells. Infection rates and SLEDAI scores were higher in Cluster C2 than in Cluster C1. The infected children had a higher proportion of B cells and a lower proportion of CD3 + T cells, CD3 + /CD4 + T cells, CD3 + /CD8 + T cells, and CD3 + /CD4-/CD8- T cells. There were no significant differences in lymphoid subsets between children in Cluster C2 and the infected groups. The area under the ROC curve of B lymphocytes in predicting SLE children with infection was 0.842. The area under the ROC curve was 0.855 when a combination of B cells, NK cells, CD4 + T cells, and CD8 + T cells was used to predict the outcome of coinfection. A high percentage of B cells and a low percentage of CD3 + T cells, CD3 + /CD4 + T cells, CD3 + /CD8 + T cells, CD3 + /CD4 + /CD8 + T cells, and CD3 + /CD4-/CD8- T cells may be associated with infection in children with SLE. B cells was used to predict the outcome of coinfection in children with SLE. Key Points •A high percentage of B cells and a low percentage of CD3 + T cells, CD3 + /CD4 + T cells, CD3 + /CD8 + T cells, CD3 + /CD4 + /CD8 + T cells, and CD3 + /CD4-/CD8- T cells may be associated with infection in children with SLE •B cells was used to predict the outcome of coinfection in children with SLE.

Dysregulated CXCL12 Expression in Osteoblasts Promotes B-lymphocytes Preferentially Homing to the Bone Marrow in MRL/lpr Mice

Peripheral circulating B-lymphocytes and B-lymphocytes in the bone marrow (BM) show different responses to lymphotoxic or immunosuppressive agents. We explored the existence of a dysregulated distribution of B-lymphocytes between peripheral and BM compartments and the underlying mechanisms. The percentage of CXC chemokine receptor 4+ B (CXCR4+ B) cells was decreased in the peripheral blood (PB) and increased in the BM of MRL/lpr mice and SLE patients. CXC chemokine ligand 12 (CXCL12) production by BM osteoblasts (OBs) derived from MRL/lpr mice and SLE patients was higher than that obtained with C57BL/6 mice or healthy subjects. MRL/lpr-derived OBs demonstrated stronger chemotactic ability toward B-lymphocytes than control OBs, and more B-lymphocytes colocalized with OBs within the periosteal zone in MRL/lpr mice. Moreover, the CXCR4+ B cell percentages were negatively correlated with the serum immunoglobulin G concentration, and the BM CXCL12 levels were positively correlated with the systemic lupus erythematosus disease activity index score and anti-double stranded DNA titer and negatively correlated with the serum complement 3 concentration. In conclusion, our results indicate a shifted distribution of B-lymphocytes between the BM and peripheral compartments in SLE patients and MRL/lpr mice and that the upregulation of CXCL12 in OBs likely contributes to enhanced chemotactic migration and anchorage of B-lymphocytes to OBs.

Antipsychotics reduces mortality in patients with neuropsychiatric systemic lupus erythematosus: a retrospective study of psychiatric consultation cases.

This study aimed to identify the presence of psychiatric comorbidities as well as investigate the relationship between psychiatric interventions for mental symptoms and mortality in patients with systemic lupus erythematosus (SLE). We retrospectively evaluated the records of 160 inpatients with SLE who required psychiatric consultation for further therapeutic intervention from 2013 to 2020 in a tertiary general hospital. We collected clinical data, including diagnoses, medications, and mortality rate. We compared clinical characteristics among the diagnosis groups and correlations between variables. A total of 138 (86.3%) patients met the diagnostic criteria for at least one mental disorder, with the most common being delirium (54.4%). The average Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score significantly differed among the diagnosis groups (p = 0.003). The mortality rate among patients with delirium was significantly higher than that in the other patient groups (x2 = 12.967, p = 0.024). SLEDAI-2K score was not significantly correlated with mortality (r = 0.123, p = 0.087). Antipsychotics use was associated with mortality (odds ratio 0.053, p = 0.021). Antipsychotic use may decrease death risk for patients with NPSLE. Early psychiatric consultation is necessary for patients with SLE who have developed or have suspected psychiatric symptoms in order to establish a comprehensive intervention plan.

Kharakter i chastota komorbidnykh urazhen sertsia u khvorykh na systemnyi chervonyi vovchak, shcho yikh diahnostovano za dopomohoiu ekhokardiohrafii, vyiavlennia i kharakterystyka yikhnikh syntropichnykh variantiv

Introduction. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by damage of different organs and systems. It has been proven that cardiovascular events are proportionally more frequent in SLE affected persons in comparison with general population of corresponding age and sex. Echocardiography is most oftenly used due to its wide availability, ease of implementation, non-invasiveness, safety for visualization of anatomical features, assessment of structure and function of the heart and main vessels. Syntropic comorbid lesions are the non-random combination of two or more syndromes or nosological units with common genetic and/or etiological and pathogenetic mechanisms in a person, which may under certain circumstances influence each other's course. The aim of the study. To investigate nature and frequency of comorbid heart lesions in patients with systemic lupus erythematosus, diagnosed by echocardiography, to identify and characterize their syntropic variants. Materials and methods. 125 patients were included in the study after signing the voluntary Consent to participate, in accordance with the requirements of the Helsinki Declaration of Human Rights, the Council of Europe Convention on Human Rights and Biomedicine, in a randomized manner with preliminary stratification based on the presence of SLE, as well as heart lesions detected by echocardiography. The study included 110 women (88.00 %) and 15 men (12.00 %) aged 18 to 74 years (mean age 42.48 ±1.12 years). All patients with SLE were stratified into five groups based on the evaluation of SLE activity (Systemic Lupus Erythematosus Disease Activity Index scale - SLEDAI). All participants were patients of the Rheumatology Department of Lviv Regional Clinical Hospital. The study included two phases, during which the nature and frequency of comorbid heart lesions, detected by echocardiography, followed by elimination and characterization of syntropic lesions were determined. Results. About half of SLE patients with comorbid heart lesions have mitral valve (MV) insufficiency, and about 1/3 of patients have mitral valve stenosis with left ventricle (LV) diastolic dysfunction. With decreasing frequency we recorded thickening of the aortic valve (AV) leaflets, increased thickness of the interventricular septum (IS), pericardial effusion, enlargement of the left atrial (LA) cavity, enlargement of the right ventricle (RV), increased thickness of the posterior wall of LV in diastole, prolapse of MV, pulmonary hypertension, insufficiency of the tricuspid valve (TV), increase in the diameter of the ascending aorta, AV insufficiency, systolic dysfunction of the LV, enlargement of the LV cavity in diastole. Mitral stenosis and aortic stenosis were found in one case only. Having studied comorbid heart lesions in SLE affected patients, we found that some of them depend statistically reliable on the activity of disease. Therefore, we consider heart valve thickening, pulmonary hypertension, pericardial effusion, and heart failure to be syntropic heart lesions in patients with SLE. Other lesions, the frequency of detection of which does not depend on the activity of SLE, was related to its accompanying diseases. Conclusions. In patients with SLE, mitral valve insufficiency, thickening of the mitral valve leaflets, diastolic dysfunction of the left ventricle, thickening of the aortic valve leaflets, increased thickness of the interventricular septum, and pericardial effusion dominate among the comorbid heart lesions diagnosed by echocardiography. Syntropic heart lesions in patients with SLE included thickening of the mitral valve leaflets, pulmonary hypertension, pericardial effusion, and mitral valve insufficiency. Keywords: systemic lupus erythematosus, comorbid lesions of the circulatory system, syntropic lesions, heart valve lesions, diagnosis, echocardiography.

Anti-C1q antibodies in lupus nephritis children with glomerular microthrombosis.

Glomerular microthrombosis (GMT) was a common vascular lesion in patients with lupus nephritis (LN). The objective of this study was to investigate the relationship between serum anti-beta2-glycoprotein I antibodies (a-β2GP1) and anti-complement 1q antibodies (a-C1q) antibodies and to investigate the possible mechanism of GMT in children with LN. The subjects were 191 children with LN diagnosed by renal biopsy in our hospital from January 2017 to January 2020. The patients were divided into GMT group and non-GMT group. The clinical manifestations, laboratory tests, renal pathology, prognosis of the two groups and the relationship between a-β2GP1 and a-C1q antibodies were observed. In 191 children with LN, 52 cases (27.23%) presented with GMT. The value of C3, haemoglobin (Hb), estimate glomerular filtration rate (eGFR) and anticardiolipin antibody (ACA) in GMT group were lower than that of non-GMT group (p < .05, p < .01). The value of serum creatinine (Scr), 24 h proteinuria (PRO), urine red blood cells (RBC), N-acetyl-β-d-glucosidase (NAG) and retinol-binding protein (RBP), a-C1q, a-β2GP1, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and renal histopathological activity index (AI) score in GMT group were higher than that of non-GMT group (p < .05, p < .01). The positive proportions of serum a-C1q and a-β2GP1 in GMT group were higher than those in non-GMT group (p < .05). According to Spearman correlation analysis, a-C1q was positively correlated with AI score, SLEDAI, a-β2GP1, GMT, LN-III and LN-IV. Hb, eGFR and a-C1q Ab were associated with the formation of GMT in children with LN. The complete proteinuria remission and renal survival in GMT group were significantly lower than those in non-GMT group (p < .05, p < .01). LN children with GMT had more severe clinical manifestations and renal pathologic damages, and poor outcome. Serum a-C1q level was positively correlated with a-β2GP1, and a-β2GP1 may be involved in the formation of GMT in children with LN, which might involve in the activation of complement classical pathway.

Mesenchymal stem cell transplantation as a potential therapy for refractory lupus nephritis: A systematic review

AbstractBackgroundLupus nephritis (LN) results in high morbidity and mortality in patients with systemic lupus erythematosus. Refractory cases of standard immunosuppressive therapy have been recorded. Mesenchymal stem cell transplantation (MSCT) shows potential use in autoimmune diseases. We aim to review MSCT in the treatment of refractory LN.MethodsPublished articles were systematically extracted from the databases in May 2022. The quality of the studies was assessed using the Oxford Centre for Evidence‐Based Medicine critical appraisal checklist.ResultsFour studies were included. All studies recruit severe or refractory LN patients and show significant improvement in post‐MSCT 24‐h proteinuria. However, the improvement of renal function after MSCT is inconsistent between studies after a 1‐month follow‐up, with one study showing deterioration of the estimated glomerular filtration rate after 3 months and one study showing an increase in serum creatinine at 6 and 9 months. Moreover, all studies show improvement in Systemic Lupus Erythematosus Disease Activity Index scores after MSCT, while two studies show that a decrease in anti‐double‐stranded DNA (anti‐dsDNA) levels after MSCT is only evident for up to 1‐month period.ConclusionsMSCT can be effective, especially in severe or refractory LN. More randomized‐controlled trials are needed to support this evidence.