Lupus

Anifrolumab (ANF) has been approved to treat extra-renal manifestations in Systemic Lupus Erythematosus (SLE) patients. Real-life data underline the excellent efficacy in skin involvement, but very little is known on other manifestations. We conducted a prospective longitudinal analysis to assess ANF efficacy in SLE-related joint involvement by using ultrasound.

We enrolled patients receiving ANF for musculoskeletal manifestations. All the patients were evaluated at baseline (T0) and after 1 (T1) 3 (T3) and 6 (T6) months of treatment.

US assessment was performed at level of bilateral hands MCP and PIP joints. According to the OMERACT, we evaluated the presence of US inflammatory features (synovial effusion/hypertrophy, Power Doppler - pD), measured by semiquantitative score (0–3), resulting in a total US inflammatory score (0–180) and total PD score (0–60).

Our cohort comprised 13 female patients. During the follow-up period, we found a significant reduction of US scores already after 1 month of treatment, with a further significant reduction after 3 and 6 months. Interestingly, after 6 months, 90% of patients showed negativization of pD signal in all the joints. Parallelly, we found a significant improvement in global disease activity indices and in DAS28crp values at all the time-points.

Our analysis, made in a real-life scenario, underlines the fast efficacy of ANF on joint synovitis as shown by the reduction in US scores in the early stages of treatment. The rapid effect on pD signal suggest the ability of this drug to prevent the development of erosive damage.

To examine patient-reported adherence to the American College of Rheumatology (ACR) reproductive health guidelines among females of childbearing age with systemic lupus erythematosus (SLE) seen at a tertiary care center.

Females with SLE aged 18–50 years who were evaluated by a rheumatologist at a tertiary care center from January 2022 to March 2024 were invited to complete an online survey. The survey assessed whether reproductive health topics had been discussed with their rheumatologists, including: contraception, pregnancy planning (i.e., medication compatibility and disease remission), and hydroxychloroquine (HCQ) use during preconception and pregnancy. Descriptive statistics were used to summarize the characteristics of all participants and reproductive health outcomes. Exploratory bivariate analyses identified factors associated with use of effective or highly effective contraception (EHEC), contraceptive counseling, and screening for pregnancy plans among females of reproductive potential.

The cross-sectional study included 102 participants (mean age 35 years). Most participants identified as White (36.3%) or Asian/Pacific Islander (32.4%). Among participants with pregnancy history after SLE diagnosis (n = 34), most reported having pregnancy planning discussions, including HCQ use, with their rheumatologist. However, fewer than one-third of all participants reported receiving contraceptive counseling by their rheumatologist in the past year. In exploratory analyses, contraceptive counseling varied significantly by race, employment status, disease duration, and who was most likely to initiate reproductive health conversations. EHEC use varied significantly by race, with numerically higher use among White participants (59.4%).

Our findings highlight specific gaps in reproductive healthcare among females with SLE, alongside areas of high adherence with guidelines. Notable differences in contraceptive use and counseling underscore important opportunities to deliver quality care in this high-risk patient population.

Systemic lupus erythematosus is a chronic autoimmune disease associated with heightened cardiovascular risk. Data on the impact of systemic lupus erythematosus on outcomes following heart failure hospitalization remain limited. This study aimed to evaluate whether systemic lupus erythematosus is independently associated with 90-days readmission and other clinical outcomes among patients hospitalized with heart failure.

We conducted a retrospective cohort study using the 2016–2017 Nationwide Readmissions Database to evaluate the association of systemic lupus erythematosus with 90-days readmission after heart failure hospitalization. Adults ≥18 years with an index admission for heart failure were included. The primary outcome was 90-days all-cause readmission. Secondary outcomes included in-hospital mortality, median length of stay, and hospitalization costs. Multivariable Cox proportional hazards were used to identify independent predictors of outcomes.

Among 1,625,731 patients hospitalized with heart failure, 9096 had comorbid systemic lupus erythematosus. Compared with non-systemic lupus erythematosus patients, those with systemic lupus erythematosus were younger (mean age 61 vs 72 years), predominantly female, and more likely to have socioeconomic disadvantage and a higher comorbidity burden. The 90-days readmission rate was significantly higher in the systemic lupus erythematosus cohort (41%) versus the non-systemic lupus erythematosus cohort (34%) (HR: 1.07; 95% CI: 1.02–1.12; p = 0.010). In-hospital mortality did not differ significantly between groups; however, mortality during readmissions was nearly doubled compared with index admissions (5.4% vs 2.9%). SLE patients had a median length of stay of 4 days (vs 4 days in non-SLE) and incurred median hospitalization costs of USD 32,872 (13% higher than non-SLE patients). Independent predictors of readmission included Medicaid insurance, weekend admission, renal failure, myocardial infarction, and discharge to a non-home setting, whereas female sex, treatment at metropolitan teaching hospitals, and comorbid hypertension or diabetes were associated with a lower risk of readmission.

Systemic lupus erythematosus is independently associated with an increased risk of 90-days readmission following heart failure hospitalization, contributing to greater healthcare utilization and costs. These findings highlight the need for tailored strategies for transitional care, multidisciplinary follow-up, and socioeconomic support.

To develop a standardized nursing protocol for pediatric hypoprothrombinemia-lupus anticoagulant syndrome (HLAS), a rare condition lacking unified clinical nursing guidelines worldwide, aiming to improve nurses’ predictive, precise and whole-course care capabilities and optimize long-term clinical outcomes in affected children.

Evidence-based nursing principles were integrated with clinical practice. After the admission and standardized management of a typical index case in March 2025, a multidisciplinary team composed of pediatric nephrology, rheumatology, laboratory medicine and nursing specialists conducted retrospective case analysis and collaborative protocol formulation, with its core innovation being the integration of thromboelastography (TEG) parameters to establish a quantitative bleeding risk stratification model. The systematic literature search covered all mainstream Chinese and English databases from database establishment to March 2025, consistent with the timeline of case admission and protocol development.

Application of this protocol in the index case enabled early identification of high bleeding risk, effectively avoiding severe bleeding events and nosocomial infections. The standardized health education and targeted psychological intervention significantly improved the disease cognition and family self-management ability of caregivers. It also transformed nurses from passive caregivers to proactive care managers.

This protocol fills the gap in specialized nursing guidelines for pediatric HLAS, standardizes clinical nursing practices, and provides a replicable methodological reference for the development of standardized nursing protocols for other rare pediatric diseases.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by heterogeneous clinical manifestations and multi-organ involvement. Current understanding of SLE pathogenesis remains limited, particularly due to the cellular and molecular diversity of immune cells across tissues. Therefore, a comprehensive review synthesizing recent advances in applying single-cell technologies to SLE research is urgently needed to bridge this knowledge gap.

Single-cell RNA sequencing (scRNA-seq) provides high-resolution transcriptomic profiling at the single-cell level. This technology facilitates the identification of rare cell subsets, the characterization of cellular states, and the elucidation of disease-specific gene expression patterns. This technology has been applied to various SLE sample types, including peripheral blood, kidney, skin, and bone marrow.

ScRNA-seq has revealed distinct immune cell subpopulations and their functional alterations in SLE, including aberrant B- and T-cell subsets, dysregulated interferon-stimulated genes, and pathogenic low-density granulocytes. Crucially, by deconvoluting this cellular heterogeneity, these high-resolution insights bridge the gap between fundamental pathogenesis and clinical application, uncovering cell-specific pathways that can be harnessed as actionable therapeutic targets and prognostic biomarkers. Integration with spatial transcriptomics and machine learning further enhances research capabilities. These tools allow for mapping disease-specific immune niches and predicting clinical outcomes. Ultimately, these findings underscore the transformative potential of scRNA-seq in decoding SLE pathogenesis and guiding future targeted therapies.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease in which dysregulated nucleic acid sensing and type I interferon responses drive autoantibody production and organ damage. Toll-like receptor 9 (TLR9) regulates these pathways, and promoter variants (rs187084 and rs5743836) may alter TLR9 expression and modulate disease susceptibility and severity. This study evaluated the association of these promoter SNPs and their haplotypes with SLE risk and clinical/laboratory features in an Iranian population.

In this case–control study, we genotyped TLR9 promoter SNPs rs187084 and rs5743836 in 140 SLE patients and 140 age- and sex-matched healthy controls using the real-time PCR-high resolution melting (PCR-HRM) assay.

Our analysis showed that the CC and CT genotypes and the C allele of the rs5743836 SNP were associated with an increased risk of SLE (P < 0.05). However, there was no association between the rs187084 SNP and the risk of SLE (P > 0.05). The combined rs187084–rs5743836 CC haplotype was associated with increased SLE risk (CC vs TT haplotype, P < 0.001). Furthermore, in the patient group, carriers of the C allele in both promoter variants exhibited earlier disease onset and more active and severe disease, as evidenced by higher levels of C-reactive protein (CRP) and anti-dsDNA, reduced complement C3 and C4, and a higher frequency of renal and neurological complications (P < 0.05).

Our data suggest that promoter variation in TLR9, specifically the rs5743836 C allele and the combined rs187084-rs5743836 CC haplotype, is linked to an increased risk of SLE and more disease activity and severe clinical presentation.

Pure membranous lupus nephritis (MLN) generally has a better kidney prognosis than proliferative lupus nephritis (PLN), but comparative data from Latin America remain limited. We evaluated clinical features and kidney outcomes of MLN in a Colombian cohort and compared them with proliferative forms.

We retrospectively included adults (≥18 years) with first biopsy-proven MLN or PLN at a Colombian tertiary center. Clinical and histopathological features were compared between pure MLN (Class V) and PLN (Class III/IV ± V). Factors associated with MLN were analyzed using logistic regression. Kidney survival was estimated using Kaplan-Meier analysis, and predictors of end-stage kidney disease (ESKD) were assessed using Cox proportional hazards regression analyses. Because death could preclude observation of ESKD, competing-risks analyses were performed using cumulative incidence functions and Fine–Gray subdistribution hazard models with death treated as a competing event.

Of 371 patients, 54 (14.6%) had MLN and 317 (85.4%) had PLN. Compared with PLN, patients with MLN have lower immunological activity, better kidney function, less active urinary sediment at biopsy, and lower modified NIH activity and chronicity indices scores. In multivariable logistic regression, higher eGFR was independently associated with MLN (OR 1.02, 95% CI 1.01−1.03), whereas anti-dsDNA positivity was inversely associated (OR 0.33, 95% CI 0.15−0.71). In univariable Cox analysis, MLN was associated with lower ESKD risk (HR 0.12, 95% CI 0.03−0.48); but this association was not confirmed in multivariable analysis, which was underpowered because only 2 ESKD events occurred in the MLN group. In competing-risks analysis, MLN was associated with a lower unadjusted subdistribution hazard of ESKD (SHR 0.13, 95% CI 0.03−0.51), but not after adjustment for baseline eGFR and modified NIH indices (adjusted SHR 0.46, 95% CI 0.11−2.00). Kaplan–Meier analysis showed higher crude renal survival in MLN than in PLN.

In this Latin American cohort, MLN exhibited a distinct baseline profile characterized by lower inflammatory activity and better-preserved kidney function at presentation. Although crude and competing-risk analyses suggested a more favorable renal trajectory for MLN, the study was underpowered to confirm an independent effect of MLN on ESKD after adjustment.

This study aimed to investigate belimumab continuation and identify clinical parameters predicting belimumab continuation in patients with systemic lupus erythematosus (SLE) in a real-world setting.

A total of 38 consecutive patients with SLE who were newly treated with belimumab at our institution from 2018 to 2024 were retrospectively analyzed. The data were censored when belimumab was discontinued or the observation period ended. Clinical and laboratory data were retrospectively collected.

The median follow-up time after starting belimumab was 37 months (IQR 12–52). The 1-year belimumab continuation rate was 29/38 (76%). During the entire observation period, 15 (39%) patients discontinued belimumab. Among the 10 patients who discontinued belimumab due to lack of efficacy, seven were switched to other biologics. The overall discontinuation rate was 13.4 per 100 person-years. Absence of serological activity (increased anti-dsDNA and/or hypocomplementemia) at baseline was a significant risk factor for belimumab discontinuation within 1 year (p = 0.034), with a relative risk of 3.43 (95% CI, 1.01–11.6). The glucocorticoid dosage was significantly reduced in the 29 patients treated with belimumab for ≥12 months (p < 0.001). Among the 33 patients who were not in the low disease activity state (LLDAS) at baseline, 19 (58%) were in the LLDAS at their final visit (p < 0.001). Belimumab was temporarily discontinued in six patients due to infection, but all patients resumed it.

The belimumab continuation rate was high among patients with SLE in real-world settings; however, the absence of serological activity at belimumab initiation was a significant risk factor for discontinuation within 1 year.

Autonomic dysfunction may arise in chronic systemic diseases, including autoimmune connective tissue disorders. This study aimed to quantify autonomic symptom burden in patients with systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), examine clinical correlates, and compare results with controls without autoimmune disease.

This cross-sectional study included 50 SLE patients, 50 SSc patients, and 35 controls. Clinical and demographic characteristics were collected during visits. Autonomic symptom burden was assessed using the Composite Autonomic Symptom Score-31 (COMPASS-31). COMPASS-31 total and subdomain scores were examined across groups and within disease groups according to clinical and serological variables. A post-hoc COMPASS-31 score >32.5 was used to define high autonomic symptom burden.

Median total COMPASS-31 scores differed across groups and were higher in both SLE and SSc than in controls (15.43 and 20.53 vs 9.03; p = 0.001). Compared with SLE, SSc had higher orthostatic and vasomotor symptom burden. Using COMPASS-31 > 32.5, high autonomic symptom burden was present in 7/50 (14%) SLE and 13/50 (26%) SSc patients, while none of the controls exceeded the cut-off. In multivariable models, serositis and joint involvement predicted high symptom burden in SLE, whereas clinically significant gastrointestinal involvement and musculoskeletal involvement were independent predictors in SSc. After adjustment for age, sex, and comorbidity, total COMPASS-31 remained higher than in controls in both SLE (β = 7.01; p = 0.013) and SSc (β = 11.24; p < 0.001).

Autonomic symptom burden appears to be higher in patients with SLE and SSc than in controls. The subgroup differences suggest that autonomic symptoms may cluster with specific organ involvement. COMPASS-31 may be a practical screening tool to identify patients who could benefit from further objective autonomic evaluation. Routine, structured assessment may support timely recognition and management of autonomic symptoms in clinical practice.

Systemic lupus erythematosus (SLE) is an autoimmune condition showing persistent profiling of inflammation and damage of organs and immune system. Amongst many biomarkers for such autoimmune diseases, Galectin-3 (Gal-3) a β-galactoside-binding lectin responsible for regulation, inflammation, and fibrosis of immune repsonses, has engrossed researchers for further investigations as a potential biomarker. However, correlation has been studied between circulating Galectin-3 levels and SLE but outcomes still remain inconsistent. Therefore, this systematic review and meta-analysis evaluated the association between circulating galectin-3 levels and SLE.

PubMed, Scopus, ScienceDirect, Web of Science, and Embase databases are extensively used for literature search. The last database search was conducted on September 6, 2025. Eligible studies included case control studies reporting circulating galectin-3 levels in individuals with SLE and healthy controls. Two independent reviewers performed study selection and data extraction. Study quality was evaluated using the Newcastle-Ottawa Scale. Comprehensive Meta-Analysis software was used for statistical analysis. Pooled effect sizes were calculated as mean differences with 95% confidence intervals. Heterogeneity was assessed using the Cochrane Q test and I² statistics, and publication bias was evaluated using Begg’s funnel plot and Egger’s regression analysis.

Seven eligible studies were included in the meta-analysis. The pooled results showed that patients with SLE had significantly higher circulating Galectin-3 levels than healthy controls (mean difference = 8.48; 95% CI: 3.84–13.12; p < 0.0001). Substantial heterogeneity was observed across studies (Tau square: 32.57, Q = 196.03; p < 0.0001, I² = 96.93%). Sensitivity analysis confirmed the stability of the overall findings. Begg’s funnel plot and Egger’s regression analysis indicated no publication bias among studies. Subgroup analysis supports the results of the overall analysis.

This meta-analysis depicts that galectin-3 may serve as a biomarker associated with SLE pathogenesis and inflammatory activity due to significantly elevated levels of circulating galectin-3 levels in patients with systemic lupus erythematosus.

Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus (SLE) lacking standardized management. This systematic review summarizes the current evidence on therapeutic interventions and clinical outcomes.

Following PRISMA guidelines, we searched six databases (e.g., PubMed, Scopus, and Web of Science) for studies on adult SLS patients published up to January 2026. Methodological quality was assessed using JBI tools.

Forty studies (111 patients) were included (30 case reports and 10 case series); 87.5% presented a low risk of bias. There was a marked female predominance (91%), with a mean age of 33.5 ± 9.8 years. All patients showed a restrictive pattern (forced vital capacity: 47–52%). Glucocorticoids were the mainstay of therapy (95–96%). Rituximab emerged as an effective primary biologic for refractory cases. Non-pharmacological interventions, such as inspiratory muscle training and non-invasive ventilation, improved diaphragmatic strength. Although symptomatic resolution occurred in 75–95% of patients, complete functional recovery (normalization of pulmonary function tests) was achieved in only 20–23% of patients. Mortality directly attributed to SLS was low (2–5.5%).

Early glucocorticoid therapy remains essential, but complete functional recovery is rare, with 80% of patients maintaining chronic restriction. For refractory cases, multidisciplinary care integrating rituximab and respiratory rehabilitation should be considered to optimize functional outcomes.

Our objective was to explore the correlation between serum (sGal-3) and urinary galectin-3 (uGal-3) levels and renal fibrosis (RF) severity in lupus nephritis (LN) patients, besides assessing their diagnostic performance for identifying moderate/severe interstitial fibrosis and tubular atrophy (IFTA).

This cross-sectional controlled study recruited 150 participants: 50 LN patients, 50 diagnosed with systemic lupus erythematosus (SLE) without LN, and 50 healthy controls. Both sGal-3 and uGal-3 levels were measured using ELISA. Histopathological assessment included evaluation of IFTA severity. Patients with LN were stratified into mild IFTA (<26%) and moderate/severe IFTA (≥26%). Moreover, we performed correlation, ROC curve, and multivariable logistic regression analyses.

LN patients showed significantly higher sGal-3 and uGal-3 levels than other groups (p < 0.001). Both biomarkers exhibited strong positive correlations with IFTA percentage (sGal-3: rho = 0.76; uGal-3: rho = 0.81; p < 0.001). Unlike those with mild IFTA, moderate/severe IFTA patients had significantly higher sGal-3 and uGal-3 levels (p < 0.001). Based on ROC analysis, uGal-3 had higher discriminatory ability for moderate/severe IFTA (AUC = 0.903) than sGal-3 (AUC = 0.801). In multivariable logistic regression, both sGal-3 and uGal-3 levels were independently associated with moderate/severe IFTA after adjusting for renal function parameters.

Both sGal-3 and uGal-3 levels are significantly associated with RF severity in LN. The uGal-3 had superior diagnostic performance for moderate/severe IFTA and may be a promising non-invasive RF biomarker in LN. Validation in large-scale prospective studies is warranted.

Systemic lupus erythematosus (SLE) features aberrant T-B cooperation and expansion of atypical memory B cells (aMBCs) characterized by the expression of CD11c and T-bet. We investigated the relationship between IL-21/IL-21R and the activation state of cTfh and Tph, with CD11c+T-bet + B cell subsets and clinical activity.

A cross-sectional study was conducted involving 40 patients with systemic lupus erythematosus (SLE) and 15 healthy subjects (HS). A multiparameter flow cytometry was used to evaluate Tph (CD4⁺CXCR5^-PD-1⁺), cTfh (CD4⁺CXCR5⁺PD-1⁺), and aMBCs (CD19⁺CXCR5^-CD11c⁺) subsets and intracellular expression of IL-17A (iIL-17A), IL-21 (iIL-21), and T-bet. The disease activity was assessed using the SLEDAI-2K.

We found an increased frequency of cTfh PD-1^vh, HLA-DR⁺, IL-21R⁺, and Tph PD-1^vh, HLA-DR⁺, and iIL-21⁺ cells in SLE patients. The aNAV T-bet⁺ cells were expanded in SLE patients. Activated T-cell states (iIL-21⁺/IL-21R⁺/PD-1^vh/HLA-DR⁺) correlated with T-bet⁺ B cells subsets. Finally, activated cTfh/Tph and aMBCs correlated with SLEDAI-2K.

Our findings provide new insights into the cooperative expression of IL-21/IL-21R and T-bet and their potential relationships with extrafollicular B-cell responses in SLE. These results highlight the IL-21/T-bet axis, offering potential avenues for biomarker development and targeted therapeutic intervention in SLE.

To determine factors associated with hydroxychloroquine (HCQ)-induced retinopathy in Puerto Ricans with systemic lupus erythematosus (SLE) and to evaluate determinants of early HCQ-induced retinopathy.

We conducted a retrospective study of adult Puerto Ricans with SLE. Patients with ophthalmologist-confirmed HCQ-induced retinopathy were compared with those without retinopathy. A subgroup analysis comparing patients with early-onset (≤5 years) versus late-onset (>5 years) retinopathy was also performed. Demographic factors, clinical manifestations, and pharmacologic treatments were analyzed using bivariate methods and logistic regression models adjusted for SLE duration.

A total of 279 patients were included; 41 had HCQ-induced retinopathy, while 238 did not. Among patients with HCQ-induced retinopathy, the mean age (SD) was 45.2 (13.2) years, and 90.2% were women. The mean (SD) SLE duration and HCQ treatment duration were 10.3 (7.7) years and 9.1 (5.8) years, respectively. Patients with HCQ-induced retinopathy were more likely to have higher daily and weight-adjusted HCQ doses and greater damage accrual, but were less likely to have proteinuria, lymphopenia, anti-dsDNA positivity, low complement levels or exposure to mycophenolate mofetil. Among patients with HCQ-induced retinopathy, 13 (31.7%) discontinued HCQ within 5 years of treatment initiation. In multivariable analysis, early-onset toxicity was associated with corticosteroid exposure.

In this cohort of Puerto Rican Hispanics with SLE, HCQ-induced retinopathy occurred in 14.7% of patients, and nearly 32% of those affected developed early-onset retinopathy. Retinopathy was primarily associated with higher daily and weight-adjusted HCQ doses, while early-onset retinopathy was associated with corticosteroid exposure. These findings provide population-specific data that may help optimize HCQ dosing and underscore the importance of regular ophthalmologic screening, even during the early years of therapy.

To compare the performance of five lupus disease-activity indices measured at a single retrospective pregnancy timepoint for discriminating a composite adverse obstetric outcome (AO), and to perform exploratory clinically interpretable categorical and renal-item analyses across indices.

Retrospective cohort at a tertiary center in Bogotá, Colombia (2012–2024). For each pregnancy, one retrospective assessment with complete clinical and laboratory information required to compute all indices was selected. AO was defined as any of: preterm birth, miscarriage, stillbirth/early fetal death, preeclampsia/eclampsia, premature rupture of membranes, postpartum hemorrhage, thromboembolism, placental abruption, or maternal death. We calculated SLEPDAI, Lupus Activity Index in Pregnancy (LAI-P), modified SLAM (m-SLAM), SLE Disease Activity Score (SLE-DAS), and BILAG2004-P. Because the dataset was retrospective and selected on complete data, we treated categorical and renal-item analyses as exploratory.

Twenty-nine pregnancies (28 women) were included; AO occurred in 18/29 (62.1%). The original continuous-score analyses showed overlapping confidence intervals across indices. Exploratory clinically interpretable analyses showed AO in 15/18 (83.3%) pregnancies with any BILAG2004-P A/B domain, 16/20 (80.0%) with SLEPDAI ≥3, and 13/14 (92.9%) with SLE-DAS >7.64. Exploratory renal analyses showed the clearest signals for BILAG2004-P renal A/B (13/14 vs 5/15; OR 26.0, 95% CI 2.61–259.31), SLEPDAI renal-item score >0 (13/13 vs 5/16; OR 56.45, 95% CI 2.81–1133.97), and the LAI-P renal item >0 (12/13 vs 6/16; OR 20.00, 95% CI 2.05–195.01).

In this small single-center cohort, active lupus was associated with adverse obstetric outcomes across disease-activity instruments. However, the study is underpowered to detect meaningful differences in discrimination between indices. Renal activity remained the most clinically relevant organ-specific signal in exploratory analyses, but these findings should be interpreted cautiously and confirmed in larger longitudinal cohorts.

This study aims to elucidate the novel role of serum receptor interacting protein kinase 3 (RIPK3)/mixed series of protein kinase-like domains (MLKL) levels in SLE and assess their correlation with clinical manifestations and serological parameters.

We employed enzyme-linked immune sorbent assay (ELISA) analysis to evaluate RIPK3/MLKL protein levels in serum from 90 SLE patients and 50 healthy controls (HC).

Our findings reveal a significant elevation of serum RIPK3/MLKL protein levels in SLE patients compared to HC (p = 0.0004 and p = 0.0005, respectively). Notably, these levels were closely associated with the disease’s clinical manifestations, notably heightened in active SLE compared to stable cases (p = 0.0312 and p = 0.0096, respectively). Furthermore, while RIPK3 protein exhibited significant upregulation in patients with lupus nephritis (LN) compared to non-LN individuals (p = 0.0017). SLE patients with high anti-nuclear antibody (ANA) titers exhibited notably higher RIPK3 levels compared to those with low ANA titers (p < 0.0001). The receiver operating characteristic (ROC) curve demonstrated diagnostic potential for serum RIPK3/MLKL, with respective areas under the curve (AUCs) of 0.6319 (p = 0.0099) and 0.7374 (p < 0.0001).

Our study illuminate serum RIPK3/MLKL proteins are exploratory biomarker candidates for SLE and necroptosis may be involved in SLE pathogenesis.

Our aim was to evaluate clinical and renal histopathological variables associated with the diagnosis of Systemic Lupus Erythematosus (SLE) in a South American cohort with Full-House (FH) glomerulonephritis (GN) in order to distinguish it from other causes of FHGN.

Observational retrospective study. Kidney biopsies performed in our hospital between 2000 and 2019 were reviewed, identifying those with a FH pattern. Clinical, analytical, and histopathological data were collected. Patients were classified as SLE with Lupus - FHGN (if they met ACR 1997 and/or SLICC 2012 and/or ACR-EULAR 2019 SLE criteria) and as non-Lupus FH GN (idiopathic or secondary). Descriptive statistics, univariate and multivariate logistic regression analysis were performed to identify factors associated with Lupus- FHGN, and Kaplan-Meier survival curves were used to compare renal survival between both groups.

181 patients with FHGN were included, 124 women (68.5%), with a mean age of 41.1 years (SD 16.0) and a median post-biopsy follow-up time of 2.9 years (IQR 0.4-6.8 years). 116 patients (64.1%) met SLE criteria (103 with extrarenal manifestations and 13 with renal-limited lupus), 52 patients presented identifiable secondary causes of FHGN and 13 remained idiopathic FHGN. Renal biopsies in Lupus - FHGN presented more frequently 3 or 4 crosses of IgG, C3 and C1q deposits (p < 0.001) and had less moderate/severe involvement of the tubulointerstitial compartment (p < 0.001), when compared with non-Lupus FHGN. In the multivariate analysis, the factors that remained associated with Lupus - FHGN were: female sex, younger age, positive ANA, anti-DNA, and 3 or 4 crosses of C1q deposits. Lupus - FHGN showed a protective effect for the development of End-Stage Renal Disease (ESRD) in the univariate analysis (HR 0.34, 95% CI 0.13-0.89) but this association was not significant in the multivariate analysis.

In this South American cohort, 35.9% of FHGN were not associated with SLE diagnosis. Female sex, younger age, positive ANA or anti-DNA antibodies and marked C1q deposits at renal biopsy were associated with SLE diagnosis.