Active Lupus Nephritis Research Articles

BCD020 rituximab bioanalog compared to standard treatment in juvenile systemic lupus erythematosus: The data of 12 months case-control study.

Systemic lupus erythematosus (SLE) is the most frequent and serious systemic connective tissue disease. Nowadays there is no clear guidance on its treatment in childhood. There are a lot of negative effects of standard-of-care treatment (SOCT), including steroid toxicity. Rituximab (RTX) is the biological B-lymphocyte-depleting agent suggested as a basic therapy in pediatric SLE. To compare the benefits of RTX above SOCT. The data from case histories of 79 children from the Saint-Petersburg State Pediatric Medical University from 2012 to 2022 years, were analyzed. The diagnosis of SLE was established with SLICC criteria. We compared the outcomes of treatment of SLE in children treated with and without RTX. Laboratory data, doses of glucocorticosteroids, disease activity measured with SELENA-SLEDAI, and organ damage were assessed at the time of initiation of therapy and one year later. Patients, treated with RTX initially had a higher degree of disease activity with prevalence of central nervous system and kidney involvement, compared to patients with SOCT. One year later the disease characteristics became similar between groups with a more marked reduction of disease activity (SELENA-SLEDAI activity index) in the children who received RTX [-19 points (17; 23) since baseline] compared to children with SOCT [-10 (5; 15.5) points since baseline, P = 0.001], the number of patients with active lupus nephritis, and daily proteinuria. During RTX therapy, infectious diseases had three patients; one patient developed a bi-cytopenia. RTX can be considered as the option in the treatment of severe forms of SLE, due to its ability to arrest disease activity compared to SOCT.

Comparison of Clinical Features, Treatment and Outcomes of Lupus Nephritis Between Patients With Late- and Early-Onset Systemic Lupus Erythematosus: A Controlled Study.

Studies have found that late-onset systemic lupus erythematosus (SLE) patients (age at diagnosis ≥ 50 years) had less severe disease and milder clinical course, but with higher organ damage and mortality rate than early-onset ones (age at diagnosis < 50 years). Unfortunately, direct comparison of renal manifestations and treatment outcomes between late- and early-onset SLE patients has been determined rarely. This study aimed to compare lupus nephritis (LN) manifestations, treatment, and outcomes between late- and early-onset in SLE patients. Medical records of SLE patients in a lupus cohort at a tertiary care university hospital, seen between January 1994 and June 2020, were reviewed. Late- and early-onset patients were matched with year at SLE diagnosis at a ratio of 1:2 (62 and 124 patients, respectively). Those with LN were identified and analyzed. At SLE onset and end of the study, LN was identified in 29 and 33 late-onset patients, respectively, and 58 and 90 early-onset patients, respectively. At the end of the study, there were 39 and 214 LN flares in late- and early-onset patients, respectively: giving an incident rate (IR) (95% confidence interval (CI))/100 person-years of LN and active LN flares of 2.00 (0.75 - 5.33) vs. 6.11 (4.32 - 8.64), P = 0.020, and 5.78 (2.75 - 12.12) vs. 18.28 (13.93 - 24.00), P = 0.001, respectively. Late-onset patients received a higher proportion of moderate- to high-dose corticosteroids, but fewer immunosuppressive drugs. In all LN flares, no difference existed between the two groups in serum creatinine, degree of proteinuria, and proportion of patients with nephrotic range proteinuria or rapidly progressive glomerulonephritis, and outcomes in terms of complete, partial or no-remission were similar between them. Mortality rate was higher in late-onset patients (27.27% vs. 6.67%, P = 0.004). This matched controlled study of year at SLE diagnosis showed that late-onset SLE patients had lower prevalence of LN and LN flares. Although they received fewer immunosuppressive drugs, their renal manifestations and treatment outcomes were no different from those in early-onset patients.

Evaluation of Type 2 SLE symptoms in patients with a range of lupus nephritis activity.

Type 2 systemic lupus erythematosus (SLE) symptoms, including fatigue, fibromyalgia, and brain fog, contribute to poor health-related quality of life (HRQoL) in patients with lupus. To test the hypothesis that Type 1 (classical inflammatory lupus) activity is associated with Type 2 SLE activity, we characterized the features of Type 2 SLE in patients with a range of lupus nephritis (LN) activity. This was a cross-sectional study of SLE patients [American College of Rheumatology (ACR) 1997 or Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria] from June 2018 to March 2020. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and the Polysymptomatic Distress Scale. Patients were divided into groups based on their renal status. Active nephritis was defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) lupus nephritis parameter. Differences across groups were analyzed by Fisher's exact test and ANOVA. In this cohort of 244 patients (93% female, mean age 43years, 58% Black), 10% had active nephritis, 35% had historical nephritis, and 55% never had nephritis (non-nephritis). Active nephritis and non-nephritis patients had a similar burden of Type 2 SLE symptoms, despite a difference in Type 1 SLE activity. Patients with active nephritis had higher Type 2 PGA (Physician Global Assessment) scores and reported more Type 2 SLE symptoms than inactive nephritis patients. Patients with inactive nephritis had the lowest Type 2 SLE activity. While Type 2 SLE symptoms are common in SLE, our findings suggest that patients with active nephritis experience significant Type 2 SLE symptoms that may be ameliorated as nephritis improves. We also observed that non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. Therefore, the etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors. Key Points • Patients with active nephritis experienced significant Type 2 symptoms that may be ameliorated as nephritis improves. • Non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. • Because etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors.

Association between metabolic syndrome and lupus nephritis activity.

Metabolic syndrome (MetS) in patients with systemic lupus erythematosus (SLE) represents an additional burden and a poor prognostic factor for the onset or worsening of atherosclerosis and cardiovascular complications. In many patients with lupus nephritis (LN), MetS is often already manifested initially. Our work aimed to determine the frequency and characteristics of MetS in patients with LN, as well as the relationship components of MetS and characteristics of disease activity. The clinical study included 67 patients with LN, 54 (80.59%) female and 13 (19.41%) male, with an average age of 42.86±14.46 years. Patients were divided into two groups: with MetS (35.82%) and without MetS (64.18%), active LN had (34 or 50.74%), and LN in remission (33 or 49.25%). We monitored clinical and biochemical parameters of interest. Comparing patients with LN collectively, as well as those with MetS and without MetS, we observed that patients with MetS were older (p=0.001), BMI (p<0.001), and systolic arterial pressure was higher (p=0.002), and smokers were more common in this group (p<0.001). In the analysis, increased triglycerides (p<0.001) and creatinine (p=0.027), and decreased albumin (p=0.050) and GFR (p=0.020) were observed in the group with MetS. MetS was present in 44.11% of patients with active LN and in 27.7% with LN in remission. The most common MetS parameter was arterial hypertension (76.6%), which correlated with GFR and creatinine; hypertriglyceridemia (47.8%), which is correlated with anti-ds-DNA Ab, erythrocyturia, proteinuria, and SLEDAI/r index; decreased HDL cholesterol (28.4%) which significantly correlated with albumin, C3 and anti-ds-DNA Ab. In our patients with LN, MetS was associated with older age, impaired kidney function, and smoking. The most common parameter of MetS was arterial hypertension and dyslipidemia, which were significantly correlated with disease activity parameters, indicating an increased risk of cardiovascular complications in this group of patients.

Adverse Impact of Systemic Lupus Erythematosus on Pregnancy Outcomes: A Saudi Arabia Retrospective Multi-Center Study.

The current study aimed to determine the pregnancy outcomes complications in patients with SLE and its association with clinical, laboratory variables, disease activity, and medication use in the Saudi population, as well as pregnancy effect on disease activity. A multicenter study included pregnant female patients with Systemic Lupus Erythematosus (SLE) from three tertiary centers in Saudi Arabia. The demographics, clinical, and laboratory variables, SLE disease activity index (SLEDAI), medication before, during, and after pregnancy, planned pregnancy, pregnancy-related outcomes, and complications in comparison to age-matched healthy female controls were noted. A total of 66 pregnant patients with SLE and 93 healthy age-matched pregnant controls were included in the study. A total of 77.3% had SLEDAI-2K ≤ 4 before conception, and 84.85% of pregnancies were planned. Age of conception, cesarean section, miscarriage, and low birth weight were statistically significant (p <0.05) higher in SLE patients than in healthy controls. Among all clinical and laboratory variables, SLEDAI-2K > 4 and active lupus nephritis during pregnancy were statistically associated with adverse outcomes (p <0.05), history of lupus nephritis was not associated with statistically adverse pregnancy outcomes. Higher SLEDAI-2K > 4 was an independent risk at least 4.87 times higher association with adverse pregnancy outcomes. (p <0.05). SLE is intricately connected with unfavorable pregnancy outcomes. The preconception of high disease activity stands as a pivotal risk factor for adverse outcomes. Despite the disease remission and meticulous planning, SLE patients frequently grapple with disease exacerbations during pregnancy, culminating in unexpected and unfavorable pregnancy-related outcomes. This underscores the intricate and multifaceted nature of managing SLE during gestation.

Potential involvement of circulating exosomal miRNA-146a in disease activity and TRAF6 gene expression in juvenile proliferative lupus nephritis

BackgroundJuvenile SLE (JSLE) is a complex autoimmune disorder that predominantly affects children and adolescents with several unique challenges, and microRNA-146a (miRNA-146a) might be an interesting anti-inflammatory molecule. Because exosomes in...

Clinico-serological associations of urinary activated leukocyte cell adhesion molecule in systemic lupus erythematosus and lupus nephritis

BackgroundLupus nephritis (LN) is one of the major complications associated with Systemic Lupus Erythematosus (SLE). Activated leukocyte cell adhesion molecule (ALCAM or CD166) is a promising urine biomarker that binds to CD6, a receptor found on lymphocytes. This binding results in T-cell activation, proliferation, and recruitment, which causes tissue inflammation and may explain the pathophysiology of LN.Aim of workInvestigate the urinary ALCAM level in SLE, study its relationship to disease activity, and clarify the association with LN activity and histopathology.Patients and methodsA case–control study was performed on 60 patients with SLE and 20 matched controls. The SLE disease activity index (SLEDAI) and the activity of renal disease (rSLEDAI) were evaluated. Renal biopsy and uALCAM levels were also investigated.ResultsUrinary ALCAM levels were higher significantly in active LN patients than inactive LN patients, active and inactive non-LN SLE, and the control group (p < 0.001). The cut-off value for identifying active and inactive LN was above 270 ng/mg (p < 0.001). ALCAM levels were greater in proliferative (class III, IV, and IV/V) than in non-proliferative (class II and V) LN (p < 0.001). ALCAM exhibited high positive correlations with SLEDAI and rSLEDAI (p < 0.001 each) and negative significant correlations with C3 (p < 0.001) and C4 (p = 0.005).ConclusionUrinary ALCAM is a sensitive biomarker evaluating LN in SLE patients. Levels above 270 ng/mg can help distinguish between active and inactive LN. ALCAM levels are correlated positively with SLEDAI and rSLEDAI but have a negative correlation with C3 and C4.Key Points• Urinary ALCAM shows promise as a biomarker for evaluating kidney dysfunction in SLE patients.• It is a non-invasive marker that can differentiate between proliferative and non-proliferative LN.• A urinary ALCAM level above 270 ng/mg can indicate active LN, while lower levels indicate inactive LN.• Urinary ALCAM levels are correlated positively with SLEDAI and rSLEDAI scores but correlated negatively with C3 and C4.

Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis.

Lupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30%-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic profiles of 225 patients with LN (573 samples) in the longitudinal Accelerating Medicines Partnership in RA/SLE cohort. Urinary biomarkers of monocyte/neutrophil degranulation (i.e., PR3, S100A8, azurocidin, catalase, cathepsins, MMP8), macrophage activation (i.e., CD163, CD206, galectin-1), wound healing/matrix degradation (i.e., nidogen-1, decorin), and IL-16 characterized the aggressive proliferative LN classes and significantly correlated with histological activity. A decline of these biomarkers after 3 months of treatment predicted the 1-year response more robustly than proteinuria, the standard of care (AUC: CD206 0.91, EGFR 0.9, CD163 0.89, proteinuria 0.8). Candidate biomarkers were validated and provide potentially treatable targets. We propose these biomarkers of intrarenal immunological activity as noninvasive tools to diagnose LN and guide treatment and as surrogate endpoints for clinical trials. These findings provide insights into the processes involved in LN activity. This data set is a public resource to generate and test hypotheses and validate biomarkers.

Association of serum Nrf2 protein levels with disease activity and renal impairment in lupus nephritis.

We aimed to investigate the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression levels, lupus nephritis (LN) disease activity, and the degree of renal injury (based on the estimated glomerular filtration rate [eGFR]) in patients with LN. We selected 40 healthy control participants and 102 patients with LN who were treated in the Second Hospital of Jilin University, China, for inclusion in this study. Patients with LN were classified into LN with high-eGFR and LN with low-eGFR groups. Nrf2 protein levels were measured in the serum and renal tissues of the participants in both groups to assess the correlation between Nrf2 protein levels and different LN disease states. There was a significantly positive correlation between serum Nrf2 protein levels, the degree of renal injury, and systemic lupus erythematosus disease activity index (SLEDAI) scores in patients with LN. Nrf2 protein levels were higher in the LN with high-eGFR group than in the healthy control and LN with low-eGFR groups. In follow-up patients in the LN high eGFR group, Nrf2 protein levels decreased significantly after remission of disease activity. Nrf2 protein expression has a dual role in patients with LN. Nrf2 protein levels not only correlate with disease activity in patients with LN, but also with the degree of kidney injury. Before implementing targeted therapy for Nrf2, evaluating both Nrf2 protein expression and the disease state in patients with LN is necessary to better identify and place each patient in an appropriate patient group.

Proximity extension assay proteomics and renal single cell transcriptomics uncover novel urinary biomarkers for active lupus nephritis

ObjectiveTo identify urinary biomarkers that can distinguish active renal involvement in Lupus Nephritis (LN), a severe manifestation of systemic lupus erythematosus (SLE). MethodsUrine from 117 subjects, comprised of inactive SLE, active non-renal lupus, active LN, and healthy controls, were subjected to Proximity Extension Assay (PEA) based comprehensive proteomics followed by ELISA validation in an independent, ethnically diverse cohort. Proteomic data is also cross-referenced to renal transcriptomic data to elucidate cellular origins of biomarkers. ResultsSystems biology analyses revealed progressive activation of cytokine signaling, chemokine activity and coagulation pathways, with worsening renal disease. In addition to validating 30 previously reported biomarkers, this study uncovers several novel candidates. Following ELISA validation in an independent cohort of different ethnicity, the six most discriminatory biomarkers for active LN were urinary ICAM-2, FABP4, FASLG, IGFBP-2, SELE and TNFSF13B/BAFF, with ROC AUC ≥80%, with most correlating strongly with clinical disease activity. Transcriptomic analyses of LN kidneys mapped the likely origin of these proteins to intra-renal myeloid cells (CXCL16, IL-1RT2, TNFSF13B/BAFF), T/NK cells (FASLG), leukocytes (ICAM2) and endothelial cells (SELE). ConclusionIn addition to confirming the diagnostic potential of urine ALCAM, CD163, MCP1, SELL, ICAM1, VCAM1, NGAL and TWEAK for active LN, this study adds urine ICAM-2, FABP4, FASLG, IGFBP-2, SELE, and TNFSF13B/BAFF as additional markers that warrant systematic validation in larger cross-sectional and longitudinal cohorts.

The role of urinary biomarker monocyte chemoattractant protein (MCP-1) in correlation with different histopathological classes of lupus nephritis in Egyptian patients

Lupus nephritis (LN) affects almost two-thirds of systemic lupus erythematosus (SLE) patients. Renal biopsy is the gold standard for the diagnosis of LN. However, repeated biopsies are not always performed in clinical practice, and they carry some risk. Therefore, minimally invasive techniques, as urinary biomarkers, are promising tools for the diagnosis and monitoring of SLE. Previous studies evaluated urinary monocyte chemoattractant protein-1 (MCP-1) in patients with SLE, reported higher levels of urinary MCP-1 in patients with active LN than non-active LN. Other studies reported higher levels of urinary MCP-1 in LN patients with proliferative forms (III and IV). This study aimed to evaluate urinary MCP-1 as a noninvasive diagnostic biomarker tool for LN, and to determine its association with different LN histopathological stages and chronicity indices. The study included 40 SLE patients with biopsy-proven LN class II, III, IV or V, and 20 patients with inactive LN as a control group. In LN active patients, the mean creatinine was 1.71 ± 0.55 mg/dl, and 0.84 ± 0.10 mg/dl in the control group. The mean MCP-1 level was 618.4 ± 294.2 ng/l in active LN patients and 120.05 ± 87.53 ng/l in inactive LN patients. The receiver operating characteristic (ROC) curve analysis indicated a better diagnostic performance of MCP-1 than conventional biomarkers. At area under the curve of 0.990, the best cut-off level was &gt;245 ng/L (sensitivity 97.5 %, Specificity 95 %). In conclusion, urinary MCP-1 distinguished active LN from inactive renal disease. It can be proposed as a good noninvasive diagnostic biomarker with a high sensitivity and specificity for detection of LN activity.

Circulating neutrophil extracellular trap remnants as a biomarker to predict outcomes in lupus nephritis

ObjectiveTo determine if the serum levels of neutrophil extracellular trap (NET) remnants (Elastase-DNA and HMGB1-DNA complexes) at the time of a lupus nephritis (LN) flare predict renal outcomes in the...

Determination of nutrition index and correlation with activity of lupus nephritis

Background/Aim. Lupus nephritis (LN), as an immuno-inflammatory kidney lesion, and the most serious manifestation of systemic lupus erythematosus (SLE), is accompanied by a disorder of the nutritional status of patients. Our goal was to determine the importance of determining and the association of parameters of nutritional status - nutritional risk index (NRI), prognostic nutritional index (PNI) and control nutritional status (CONUT) with standard parameters of LN activity. Methods. The clinical study included a group of 92 subjects. 67 patients had LN (34 patients had LN active disease , the LNa group, and 33 patients were in LN remission, the LNr group) and 25 healthy subjects (control group). In addition to standard laboratory parameters, LN activity parameters, derived parameters were also determined: PNI=10 x albumin value (g/dL) + 0.005 x number of peripheral lymphocytes (/mm3); NRI = 1.519 ? serum albumin, g/dL + 41.7 ? weight (kg)/ideal body weight ( kg); CONUT score = serum albumin + total lymphocyte score + total cholesterol. Results. A statistically significant difference between all three groups was observed for the PNI (p=0.001) and for the CONUT score (p=0.000), while the NRI did not have a significant difference. Statistical significance was found for the correlation of PNI in the LNa group, with the levels of albumin, complement C3 and C4, and a significant negative correlation with the value of anti-ds-DNA Ab. NRI correlated with statistical significance only with proteinuria in the LNa group. CONUT showed significant correlations with the most of the parameters for disease activity: negative correlation with albumin and complement C3 (p = 0.000), and positive correlation with anti -double strand (ds) - DNA Antibody (p=0.002),with Systemic Lupus Erythematosus Disease Activity Index/renal (SLEDAI/r) and with proteinuria/24 hrs (p=0.000). Conclusion. In our group of patients, a statistically significant difference was observed between the groups for the nutrition score CONUT. and the PNI. Their correlation with standard parameters of active disease was significant for most parameters in the group of patients with LNa.

The Role of urinary kidney injury molecule 1 (KIM-1) in monitoring the treatment response in Egyptian Lupus Nephritis Patients

Lupus nephritis (LN) affects almost two-thirds of systemic lupus erythematosus (SLE) patients. Despite initial aggressive therapy, up to 25% of patients with LN will progress to permanent renal damage. Conventional serum markers for LN lack the sensitivity of an ideal biomarker. Urinary kidney injury molecule-1 (UKIM-1) is an excellent biomarker for early diagnosis of acute kidney injury and predicting renal outcomes. This study intended to determine the predictive performance of UKIM-1 among LN patients in response to induction therapy by assessing and correlating its levels with renal disease activity. The study included 60 SLE patients divided into 20 SLE patients with active lupus nephritis, 20 SLE patients with inactive lupus nephritis, and 20 lupus patients without nephritis as controls. The study was completed after six months from induction treatment. UKIM-1 was measured by an enzyme linked immunosorbent assay at baseline, three-month follow-up and after complete induction therapy. At baseline, the mean serum creatinine and mean UKIM-1 were 1.7 ±0.7 mg/dL and 10.3 ±1.2 ng/dL, respectively in active LN patients. The mean UKIM-1 levels of complete response and partial response groups were 9.8 ±0.9 ng/mL and 11.3 ±1.0 ng/mL respectively. Based on receiver operating characteristics curve analysis, we found a better diagnostic performance of UKIM-1 to predict response to induction treatment, outperforming conventional biomarkers. The sensitivity and specificity were 84.6% and 85.7 %, respectively at an area under the curve of 0.896 and the best cut-off level was ≤10.6 ng/mL. In conclusion, UKIM-1 performed better than conventional biomarkers in predicting response to treatment of active LN.

Anti-C1q antibodies: a biomarker for diagnosis and management of lupus nephritis. A narrative review.

Nephritis is a frequent and severe complication of Systemic Lupus Erythematous (SLE). The clinical course of lupus nephritis (LN) is usually characterized by alternating phases of remission and exacerbation. Flares of LN can lead to deterioration of kidney function, necessitating timely diagnosis and therapy. The presence of autoantibodies against C1q (anti-C1qAb) in the sera of SLE patients has been reported in various studies. Some research suggests that the presence and changes in the titer of anti-C1qAb may be associated with the development of LN, as well as with LN activity and renal flares. However, theexact role of anti-C1qAb in LN remains a subject of debate. Despite variability in the results of published studies, anti-C1qAb hold promise as noninvasive markers for assessing LN activity in SLE patients. Measuring anti-C1qAb levels could aid in diagnosing and managing LN during periods of both inactive disease and renal flares. Nevertheless, larger controlled trials with standardized laboratory assays are necessary to further establish the utility of anti-C1qAb in predicting the reactivation and remission of LN and guiding treatment strategies.

Clinicopathological Assessment of Modified Activity and Chronicity Indices in Lupus Nephritis at a Teaching Hospital in Mysore, India

Introduction: In 20-49% of patients with Systemic Lupus Erythematosus (SLE), Lupus Nephritis (LN) is a major complication and, therefore, an important prognostic determinant of SLE. The Activity and Chronicity Indices (AI and CI), used as adjuncts to the histological classification of LN, assist in identifying patients who will benefit from immunosuppressive therapy. Aim: To investigate the correlation of AI and CI in patients with biopsy-proven LN with clinical and laboratory findings. Materials and Methods: A cross-sectional study was conducted as the Departments of Pathology and Nephrology, JSS Medical College and Hospital Mysore, India from January 2023 to March 2023, by retrieving the data of 56 patients with biopsy proven LN. AI and CI were assessed and classified. Data from multiple groups were compared using Pearson’s chi-square test, and between two groups using independent samples t-test with Statistical Package for Social Sciences (SPSS) version 21.0. Pearson’s correlation coefficient (r-value) was calculated using Microsoft excel 2021. Results: Renal biopsies from 56 cases with biopsy-proven LN were studied, with a mean age of 28±10.30 years and a M:F ratio of 1:10.2. Of the 56 biopsies studied, active lesions were seen in 47 (83.9%) and chronic lesions in 21 (37.5%). AI showed statistical significance with hypertension (p=0.049) and haematuria (p=0.005), with proteinuria (p=0.001, r=0.72), serum creatinine (p=0.037, r=0.62), and blood urea nitrogen (p=0.003, r=0.55) showing a statistically significant positive correlation. CI showed a statistically significant positive correlation with proteinuria (p=0.028, r=0.039) and serum creatinine (p=0.010, r=0.58). Both AI and CI showed statistical significance with the degree of renal insufficiency, with CI (p=0.008) displaying a stronger statistical significance than AI (p=0.012). Conclusion: In conclusion, the management and prognosis of patients with suspected LN are greatly facilitated through information obtained from renal biopsy, especially AI and CI, which are useful guides to treatment. It is important to study renal biopsy for the constellation of features in LN for better patient management.

Fragility of randomised controlled trials for systemic lupus erythematosus and lupus nephritis therapies

ObjectiveWe aimed to evaluate the robustness of phase III randomised controlled trials (RCTs) for SLE and lupus nephritis (LN) using the fragility index (FI), the reverse FI (RFI) and the...

Urinary tissue factor (uTF), tissue factor pathway inhibitor (TFPI) and plasmin as novel biomarkers in early diagnosis of lupus nephritis

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, with multi systematic affection. Lupus nephritis (LN) is the most frequent cause of renal damage in SLE patients with variable presentations that may progress to end stage renal failure. Coagulation disorders are frequently reported in SLE and LN with higher mortality rates. Renal biopsy is an invasive process, and the existing indicators for LN diagnosis and activity are unreliable. New urinary biomarkers with significant validity, safety, and accuracy are the current focus of most studies. Our study sought to assess the value of urinary tissue factor (uTF), tissue factor pathway inhibitor (TFPI), and plasmin as biomarkers for the early identification and detection of LN and its activity. This was a cross-sectional study, included 100 subjects (80 SLE patients, and 20 healthy controls), they were recruited from the Internal Medicine department, Rheumatology and Nephrology units and outpatient’s clinics at Assiut University hospital between the period of 2020 and 2022. All patients underwent full history taking, clinical evaluation, and activity scoring calculation and laboratory investigations. The results showed that the best diagnostic accuracy of LN was observed with TFPI (90% accuracy, sensitivity 80% and specificity 95% with p&lt;0.001 at cutoff point of &gt;193.2 ng/ml), followed by uTF (75.4% overall accuracy at cut off point of &gt;12.6 ng/ml, sensitivity 90% and specificity 68% with p&lt; 0.001) and plasmin (70.3% accuracy at cut off point of &gt;30.5 ng/ml, sensitivity 55% and specificity 78% with p&lt; 0.001). Urinary TFPI was the best predictor of LN occurrence with odd ratio of 4.34, (p&lt; 0.001). In conclusion urinary TFPI could be used as a diagnostic marker for LN with high accuracy and an early predictor of LN.

Lupus exacerbation in ovalbumin-induced asthma in Fc gamma receptor IIb deficient mice, partly due to hyperfunction of dendritic cells.

Although allergy might be another factor that exacerbates lupus as demonstrated by several epidemiologic studies, the direct correlation between lupus activities and allergy is still in question. To explore the correlation between allergic reaction and lupus activities. The allergic asthma model using ovalbumin (OVA) administration in wildtype (WT) and Fc gamma receptor IIb deficient (FcgRIIb-/-) mice (a lupus-prone model) together with in vitro experiments on bone marrow-derived dendritic cells (DCs) were performed. At 2-weeks-post OVA, both WT and FcgRIIb-/- mice demonstrated similar allergic reaction as indicated by an elevation of IgE and IL-4 in serum with asthma-liked lung histology (lung weight, inflammatory score, and bronchial thickness) with increased spleen weight. Apoptosis in the lungs and spleens (activated caspase 3 immunohistochemistry) was detected only in OVA-administered FcgRIIb-/- mice. Surprisingly, OVA-administered FcgRIIb-/- mice, demonstrated active lupus nephritis, as indicated by anti-dsDNA, proteinuria, and renal immune complex deposition (immunohistochemistry analysis) implying an impact of allergy on lupus activities. Meanwhile, serum creatinine and gut permeability defect (FitC-dextran assay and endotoxemia) were not different between the FcgRIIb-/- mice with OVA versus with control. In parallel, FcgRIIb-/- DCs were more susceptible to activations by OVA and lipopolysaccharide (LPS) than WT DCs as demonstrated by CD80 with major histocompatibility complex II (MHC II) using flow cytometry analysis. OVA-induced allergy in FcgRIIb-/- mice exacerbated lupus activity, possibly due to hyper-responsiveness of FcgRIIb-/- DCs over WT from the loss of inhibitory FcgRIIb. The proper control of allergy might be beneficial for lupus.

Serum IgE anti-dsDNA autoantibodies in patients with proliferative lupus nephritis are associated with tubulointerstitial inflammation

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the overproduction of multiple autoantibodies. Lupus nephritis (LN), the most common cause of morbidity and mortality, requires early detection. However, only a limited number of serum biomarkers have been associated with the disease activity of LN. Serum IgE anti-dsDNA autoantibodies are prevalent in patients with SLE and may be associated with the pathogenesis of LN. In this study, serum samples from 88 patients with biopsy-proven proliferative LN were collected along with complete clinical and pathological data to investigate the clinical and pathological associations of anti-dsDNA IgE autoantibodies using ELISA. This study found that the prevalence of IgE anti-dsDNA autoantibodies in patients with proliferative LN was 38.6% (34/88). Patients with anti-dsDNA IgE autoantibodies were more prone to acute kidney injury (17/34 vs. 14/54; p = .025). Levels of anti-dsDNA IgE autoantibodies were associated with interstitial inflammation (r = 0.962, p = .017). Therefore, anti-dsDNA IgE autoantibody levels are associated with tubulointerstitial inflammation in patients with proliferative LN.