Lupus最新文献

ObjectiveTo evaluate the concordance of four anti-dsDNA antibody detection methods-Crithidia luciliae indirect immunofluorescence test (CLIFT), enzyme-linked immunosorbent assay (ELISA), acridine ester direct chemiluminescence immunoassay (CLIA), and digital liquid chip method (DLCM)-and to assess their diagnostic efficacy in systemic lupus erythematosus (SLE) patients.MethodsA total of 285 serum samples were collected, including 170 SLE patients, 39 with non-SLE autoimmune diseases (AIDs), 28 with non-AIDs, and 48 undiagnosed cases. The concordance and diagnostic performance of anti-dsDNA antibody methods were analyzed.ResultsThe diagnostic performance showed that DLCM exhibited the highest sensitivity (86.87%), while CLIA demonstrated the highest specificity (94.03%). The area under the receiver operating characteristic (ROC) curve (AUC) was ranked as CLIFT < ELISA < CLIA < DLCM (AUC = 0.938). Anti-dsDNA antibodies detected by both CLIFT and DLCM correlated well with the SLE disease activity index (SLEDAI), while CLIFT and CLIA were significantly correlated with lupus nephritis. Utilizing ROC curve-derived cut-off values, the overall concordance of CLIFT and other methods ranged from 80.14% to 82.58% (kappa > 0.6, P < 0.001), and the concordance between quantitative methods ranged from 89.55% to 91.29% (kappa > 0.8, P < 0.001).ConclusionCLIFT, ELISA, CLIA, and DLCM all showed impressive diagnostic efficacy in detecting anti-dsDNA antibodies. CLIFT shows a strong correlation with SLE activity and lupus nephritis. DLCM, a relatively new method, also showed excellent performance and could be integrated into clinical laboratory workflows for anti-dsDNA antibody testing.

ObjectiveLupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE). Existing data on LN in Saudi Arabia are primarily retrospective and derived from single centers. Therefore, this systematic review presents a unique and comprehensive analysis of the disease characteristics and outcomes of LN in Saudi Arabia.MethodA systematic search of MEDLINE, ScienceDirect, Embase, Cochrane, and PubMed databases was conducted up to April 2024. Eligible articles reporting on LN in Saudi Arabia were included, and disease characteristics and outcomes were analyzed.ResultsA total of 36 studies met the inclusion criteria. The prevalence of LN among SLE patients in Saudi Arabia ranged from 19% to 55%, with biopsy-proven LN reported in 11% to 42.7% of cases. Females accounted for 66% to 94.9% of patients, with a mean age at diagnosis between 23.8 and 39.7 years. Hypertension was present in 45.8% to 62.9% of patients, with nephrotic-range proteinuria in 20.7% to 58.5% and mean serum creatinine levels between 60 and 112.68 µmol/L. Class IV LN was the most common histopathological finding, occurring in up to 72% of cases. Complete remission was achieved in up to 81.5% of patients within 12 months, though lower remission rates were observed in those with proliferative LN. End-stage renal disease (ESRD) rates ranged from 5.5% to 30.7%, with proliferative LN, older age, and hypertension being significant predictors of progression to ESRD. Five-year survival rates ranged from 92% to 96%, while 10-year survival reached 95%. Infection and renal failure were the leading causes of mortality.ConclusionLN is highly prevalent in lupus Saudi patients, with Class IV LN being the most common and associated with poor outcomes. Although survival has improved, many patients still progress to ESRD. Prospective trials are needed to evaluate outcomes in the current era of biological therapies.

BackgroundSystemic Lupus Erythematosus (SLE), a complex autoimmune disorder characterized by altered immune regulation, particularly involving B cells, which exhibit increased survival and developmental dysregulation. This study aimed to investigate the expression of IRF4, IRF8, SP1, and PU.1 in B cells of SLE patients, as these factors are known to play critical roles in the development, function, and differentiation of B cells.MethodsB cells were isolated, cultured, and activated using anti-IgM. The mRNA expression of IRF4, IRF8, SP1, and PU.1 was assessed using reverse transcription polymerase chain reaction (RT-PCR) at baseline and after B cell activation. Correlations between transcription factor expression and clinical parameters were analyzed.ResultsUpon B cell activation, IRF4 expression increased significantly in SLE patients, unlike at baseline, where no changes were observed between groups. IRF8 expression was significantly raised in active SLE and increased upon activation. SP1 expression remained stable across all groups and conditions. PU.1 gene expression was higher in active SLE at baseline and increased further upon B cell activation. Positive correlations were found between IRF4 and IRF8, as well as between PU.1 and SP1. PU.1 expression correlated with SLE disease activity indices.ConclusionIRF4, IRF8, and PU.1 expression in B cells is altered in SLE. PU.1 shows a positive correlation with SLEDAI and anti-dsDNA titers. These findings highlight their potential roles in the pathogenesis of SLE in B cells.

BackgroundAntiphospholipid syndrome (APS) predisposes patients to thrombosis and cardiac valve lesions such as Libman-Sacks endocarditis. These vegetations are sterile yet can provide a nidus for infection; the risk of infective endocarditis (IE) and other serious infections in APS patients remains poorly quantified in large populations, representing a knowledge gap.ObjectiveTo quantify the risk of the primary outcome, IE, and secondary outcomes of MRSA sepsis and MSSA sepsis, associated with APS using a large, nationally representative inpatient database.MethodsWe conducted a cross-sectional study using the National Inpatient Sample (NIS) database from 2016 to 2020. Hospitalized patients aged 18-75 with APS were compared to those without APS. Patients with major pre-existing risks for IE or significant confounders (e.g., prosthetic valves, specific congenital/rheumatic heart diseases, ESRD) were excluded. Multivariable logistic regression was used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs).Results297,459 patients fitted our inclusion criteria. On multivariate analysis, APS was significantly associated with over double the odds of IE (aOR 2.03; 95% CI 1.22-3.37). Importantly, APS also conferred considerably increased risks of MRSA sepsis (aOR 1.75; 95% CI 1.18-2.58) and MSSA sepsis (aOR 1.86; 95% CI 1.28-2.70).ConclusionAPS emerged as a significant independent risk factor for IE, Methicillin-resistant (MRSA), and Methicillin-sensitive Staphylococcus aureus (MSSA) sepsis. This suggests a broader vulnerability to infection, possibly linked to underlying endothelial dysfunction or immune dysregulation inherent in APS. These findings highlight the critical need for increased clinical suspicion, vigilant monitoring, and potentially tailored prophylactic or treatment approaches for severe infections in patients with APS.

BackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by the production of autoantibodies that target most of the organ systems and lead to their dysfunction. The exact etiology of SLE remains unclear; however, genetic and environmental factors are believed to play significant roles. Viral infections, particularly Epstein-Barr virus (EBV), have been implicated as environmental triggers in SLE pathogenesis however, the observations remained inconsistent among studies and populations. The present study uses a meta-analysis approach to explore the prevalence of EBV infection in the general population and their role in the pathogenesis of SLE.Materials and MethodsVarious databases such as PubMed, Scopus, and ScienceDirect were searched to obtain eligible studies based on predetermined inclusion and exclusion criteria. The Newcastle-Ottawa Scale (NOS) was used for quality assessment of the eligible studies, and Comprehensive Meta-Analysis (CMA) v4 software was used for the analysis. Publication bias was assessed with funnel plots and Egger's regression, while heterogeneity was evaluated with Cochrane Q and I² statistics.ResultsIn the present investigation, a total of 28 studies comprising of 3926 healthy controls and 2968 SLE patients were included. EBV infections were prevalent in the healthy controls. While comparing the frequency of EBV DNA or antibodies positivity, the SLE patients had a higher positivity rate than the healthy controls, indicating that EBV infection is a risk factor for developing SLE. Furthermore, the sensitivity analysis also revealed that the meta-analysis was robust.ConclusionThe majority of healthy subjects were previously exposed to EBV, and the infection could be a potential risk factor in SLE pathogenesis. However, future research is required to elucidate the possible mechanisms of EBV reactivation in SLE patients and examine potential preventive measures, such as antiviral therapies, in mitigating SLE risk.

ObjectivesThe aim of this study was to compare the clinicopathological characteristics and outcomes of lupus nephritis (LN) between late-onset and early-onset systemic lupus erythematosus (SLE) patients.MethodsWe reviewed the clinical, serological and histological characteristics of all patients with LN admitted to our nephrology unit between 2007 and 2024. Our patients were divided into two groups according to their age at diagnosis: Early-onset SLE (younger than 50 years) and late-onset SLE (50 years or older).ResultsA total of 231 patients were recruited, of whom 43 had late-onset SLE and 188 had early-onset SLE. The mean age at diagnosis of SLE was 58.36 ± 7.61 years in the late-onset SLE group and 29.23 ± 9.03 years in the early-onset SLE group. There was no difference in the time from SLE diagnosis to LN. Compared with early-onset group, late-onset group had a higher prevalence of discoid rash but a lower frequency of leukopenia. Late-onset patients had higher serum creatinine levels and lower prevalence of anti-SSA and anti-RNP antibodies. The frequency of class VI LN was statistically significantly higher in the late-onset group. The use of oral corticosteroids, hydroxychloroquine and immunosuppressive drugs was significantly lower in late-onset SLE patients than in early-onset SLE patients. The latter were significantly less likely to progress to chronic kidney disease.ConclusionOur results indicate that SLE patients have different clinical, serological and histological manifestations depending on the age at onset of the disease. Late-onset SLE patients are more likely to have rheumatoid arthritis at onset. They have more severe chronic renal lesions and a worse renal outcome.

ObjectivesAim of this study was to investigate the expression of interleukin (IL)-40, a cytokine associated with B cells homoeostasis and immune response, in Systemic lupus erythematosus (SLE) and SLE associated nephritis.Methods32 patients with SLE and 21 controls were enrolled. Serum concentration of IL-40 was assessed by ELISA and cellular sources of IL-40 were determined by flow-cytometry. An in vitro assay with recombinant IL-40 (rIL-40) was performed to detect the effect on cytokine production from peripheral blood mononuclear cells (PBMC). In kidney biopsies obtained from patients with lupus nephritis (LN) immunofluorescence was performed to assess IL-40 expression and detect its cellular sources at tissue level.ResultsSerum IL-40 levels show a decreasing trend in SLE with LN, compared with SLE without LN and controls. No differences between SLE and controls were evidenced in urinary IL-40 levels; in the percentage of CD3⁺IL40⁺, CD19⁺IL40⁺ and CD14⁺IL40⁺; and in the production of pro-inflammatory cytokines by PBMC stimulated with rIL-40. IL-40 expression was markedly increased in kidney tissue from LN patients, with a significant increase of IL40⁺ cells in LN samples compared to controls, as confirmed by the quantification analysis.ConclusionTo the best of our knowledge this is the first demonstration of IL-40 expression at kidney level in SLE. These preliminary data suggest a possible role of IL-40 in LN. In particular, IL-40 could be a marker of kidney tissue damage, although its specific mechanism of action needs to be further elucidated.

BackgroundToxic epidermal necrolysis like lupus erythematosus (TEN-like LE) is a dermatological emergency associated with significant morbidity and mortality. It requires prompt recognition and differentiation from its mimics including drug induced toxic epidermal necrolysis, erythema multiforme, drug rash with eosinophilia and systemic symptoms, and reactive infectious mucocutaneous eruptions.ObjectiveTo assess systemically the clinical, pathological, and immunological features of patients with TEN-like LE.MethodsWe performed a structured search systematic review from April-May 2024, of studies on TEN-like LE published between 1977 and 2024., searching PubMed, Medline, Embase, SCOPUS, VHL, ProQuest, clinicaltrials.gov, COCHRANE, POPLINE, ISI, mRCT, UC library, and ResearchGate.ConclusionThere were 16 case series and 52 case reports/conference papers yielding 112 unique cases. The mean age was 43.39 years, and 86.6% of cases were female. TEN-like LE was the presenting manifestation of lupus erythematosus (LE) in 48.21% of patients. Antinuclear antibody (ANA) was positive in all 109 patients where it was reported with SSA/Ro being most commonly positive (60.55%), followed by dsDNA (50%). Lesions were reported to be photodistributed in 78.57%, palmoplantar involvement was seen in 20.54%, and mucosal involvement was seen in 56.25%, with 26.78% patients having significant mucosal involvement. Lupus non-specific lesions were observed in 25% patients. Anemia, pulmonary and GI involvement were positively associated with hemodynamic instability, and anti-Ro antibodies were negatively associated. Positive dsDNA, La positivity, and low C4 were associated with increased odds of systemic involvement, whereas Ro positivity was associated with reduced odds. Seven patients had a paraneoplastic association. TEN-like LE can be the first manifestation of LE in up to half of cases. Photodistribution, lupus non-specific lesions, ANA positivity, or change in ANA type/titre can be important diagnostic clues. Unlike previously believed, mucosal involvement is not uncommon and can be severe.

ObjectivesThis study aims to investigate CD4⁺ central memory T cells (CD4⁺ TCM) levels in childhood-onset systemic lupus erythematosus (cSLE) and their association with disease activity, clinical features, and treatment responses.MethodsA total of 202 children with newly diagnosed, untreated rheumatic diseases were recruited, comprising 64 cases of cSLE, 71 cases of juvenile idiopathic arthritis, 31 cases of juvenile dermatomyositis, 36 cases of autoinflammatory diseases, and 22 healthy controls. Lymphocyte subsets were analyzed using multi-color flow cytometry, and clinical data and laboratory test results were collected. The correlation between CD4⁺ TCM levels and SLEDAI scores, clinical manifestations, autoantibodies, and kidney injury markers was examined. Subsequently, 21 cSLE patients underwent follow-up assessments and retesting post-treatment.ResultsThe proportion of CD4⁺ TCM (44.3 ± 11.5%) in cSLE was significantly higher compared to those with other pediatric rheumatic diseases (p < .05). A negative correlation was observed between the level of CD4⁺ TCM and the SLEDAI-2000 score (r = -0.255, p = .021), indicating that higher disease activity was associated with lower CD4⁺ TCM levels. Furthermore, CD4⁺ TCM levels were negatively correlated with oral ulcers (r = -0.285, p = .011) and positively correlated with leukopenia (r = 0.302, p = .008). In terms of laboratory indicators, CD4⁺ TCM showed negative correlations with anti-dsDNA antibodies (r = -0.294, p = .009) and anti-histone antibodies (r = -0.232, p = .033), while exhibiting a positive correlation with anti-Sm antibodies (r = 0.245, p = .025). Additionally, CD4⁺ TCM demonstrated significant negative correlations with early renal injury markers, urinary transferrin (r = -0.315, p = .008), and urinary microalbumin (r = -0.284, p = .015). CD4⁺ TCM was strongly negatively correlated with CD4⁺ Naive cells (r = -0.831, p < .001), positively correlated with other memory cell subsets, and negatively correlated with IFN-α levels (r = -0.364, p = .031). Longitudinal analysis revealed a time-dependent biphasic pattern in CD4⁺ TCM levels. Cyclophosphamide-treated patients showed significantly increased CD4⁺ TCM levels compared to non-cyclophosphamide groups (p = .034).ConclusionsCD4⁺ TCM likely plays a central immune regulatory role in cSLE, with its levels closely associated with disease activity, specific autoantibody production, and early organ damage. Post-treatment changes in CD4⁺ TCM levels may indicate therapeutic efficacy and suggest their potential as biomarkers, offering a fresh perspective on immune memory regulation in cSLE and exploring novel treatment approaches.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multisystem involvement. Lupus Nephritis (LN) is the most serious presentation. Cardiovascular complications in SLE and LN can cause significant morbidity and mortality. An echocardiographic (ECHO) screening allows early detection and intervention, so that early treatment can be provided.MethodThis cross-sectional analytical study evaluated 50 children with LN at the Department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2017 to July 2023. All patients fulfilled the Systemic Lupus International Collaborating Clinics (SLICC, 2012) criteria for SLE diagnosis and had evidence of renal involvement. Cardiac evaluation was performed by color doppler echocardiography. Systemic lupus erythematosus disease activity index (SLEDAI) was used to see the disease activity.ResultsThe mean age of presentation was 12.4 ± 2.79 years, with a male-to-female ratio of 1:3. Cardiac abnormalities were found in 20 patients (40%), with tricuspid regurgitation being the most frequent (38%), followed by pericardial effusion (28%), pulmonary hypertension (24%), and mitral, aortic and pulmonary regurgitation in descending order. Abnormal echocardiographic findings were significantly associated with higher SLEDAI scores and lower C3 levels.ConclusionsCardiac abnormalities are prevalent in pediatric LN and valvular dysfunction particularly tricuspid regurgitation being the most common followed by pericardial effusion and pulmonary hypertension. These abnormalities correlate with higher disease activity and lower C3 levels, emphasizing the critical need for routine echocardiographic screening for early detection and management.