Improving lupus care index documentation in patients with childhood-onset systemic lupus erythematosus.

Introduction: Childhood-onset systemic lupus erythematosus (c-SLE) presents unique challenges due to increased risk for severe morbidity and mortality compared to adult-onset SLE. Effective disease management relies on accurate disease assessment and documentation. Our project aimed to improve the documentation of the Lupus Care Index (LCI), a disease assessment bundle, by implementing a quality improvement (QI) initiative. Methods: A QI project was conducted at Nationwide Children's Hospital (NCH), targeting patients with c-SLE. The LCI, comprising the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2k) Physician Global Assessment (PGA) and patient-reported pain score, was introduced to capture comprehensive disease assessment. Interventions included provider education, standardization of documentation procedures, and electronic health record (EHR) modifications. Automated reports tracked documentation rates, and Pareto charts identified areas for targeted interventions. Results: Baseline analysis revealed incomplete documentation of LCI components in only one-third of c-SLE patients. Following interventions, documentation rates improved from 38% to 90%, with sustained improvement over at least a year. Discussion: Enhancing documentation of LCI in patients with c-SLE is crucial for optimizing disease management. Our quality improvement initiative demonstrated the feasibility of improving documentation practices through targeted interventions and system modifications. Future research should explore the impact of comprehensive documentation on clinical outcomes in pediatric lupus patients. Improving documentation of LCI in patients with c-SLE is essential for optimizing care delivery and clinical outcomes; our QI initiative highlights the effectiveness of systemic interventions in enhancing documentation practices and underscores the importance of continued efforts to improve pediatric lupus care.

Monogenic lupus - from gene to targeted therapy.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by loss of tolerance to nuclear antigens. The formation of autoantibodies and the deposition of immune complexes trigger inflammatory tissue damage that can affect any part of the body. In most cases, SLE is a complex disease involving multiple genetic and environmental factors. Despite advances in the treatment of SLE, there is currently no cure for SLE and patients are treated with immunosuppressive drugs with significant side effects. The elucidation of rare monogenic forms of SLE has provided invaluable insights into the molecular mechanisms underlying systemic autoimmunity. Harnessing this knowledge will facilitate the development of more refined and reliable biomarker profiles for diagnosis, therapeutic monitoring, and outcome prediction, and guide the development of novel targeted therapies not only for monogenic lupus, but also for complex SLE.

Decreased Serum CTRP3 level was associated with connective tissue diseases.

Objective: Complement C1q tumor necrosis factor-related protein 3 (CTRP3) and 9 (CTRP9) are two of the most extensively studied adipokines, known for their diverse biological functions. However, it remains unclear whether serum levels of CTRP3 or CTRP9 are associated with connective tissue diseases (CTD). Methods: Serum CTRP3 and CTRP9 levels were measured by enzyme-linked immune sorbent assay (ELISA) and analyzed in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjogren's syndrome (pSS), ankylosing spondylitis (AS), undifferentiated connective tissue disease (UCTD), as well as in healthy controls (HCs). Results: Serum CTRP3 levels were all significantly lower in patients with RA, SLE, pSS and AS compared with HCs. However, there were no significant differences in serum CTRP9 levels between patients with RA, SLE, pSS, or AS and HCs. In pSS patients, CTRP3 showed a weak correlation with blood glucose, creatinine, and urine acid in pSS patients, while no correlations were observed between serum CTRP3 levels and clinical or laboratory indices in RA, SLE or AS patients. Stable associations between CTRP3 and RA, SLE, pSS and AS were evaluated using multivariate logistics regression analysis. Receiver operating characteristic (ROC) curves were plotted to evaluated CTRP3 as a marker for RA, SLE, pSS and AS, yielding area under curve (AUC) values of 0.691, 0.727, 0.658 and 0.694, respectively. Conclusion: Decreased serum CTRP3 levels were associated with RA, SLE, pSS and AS.

Anti-Smith Antibodies as a Predictive Factor for Developing Lupus Nephritis in Systemic Lupus Erythematosus Patients: A Systematic Review.

Lupus nephritis (LN) is the most frequent and lethal complication of systemic lupus erythematosus (SLE), often presenting with subtle or no initial symptoms. Therefore, it is crucial to identify SLE patients who are at risk of developing LN to ensure they receive timely intervention. Significant scientific efforts have been made to identify various genes and antibodies that could increase the risk of LN. Our objective is to review the role of anti-Smith antibodies in this disease and evaluate their potential as a predictive marker for LN. This review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched for different study types from 2019 onwards as per our inclusion and exclusion criteria, to look for the significance of anti-Smith antibodies. The following databases were used: PubMed, PMC, Google Scholar, Science Direct, and Scopus. Twenty-two studies were checked for eligibility, of which 17 studies passed, based on the commonly used quality assessment tool for each of the corresponding studies. The study results indicated that anti-Smith antibodies are highly specific for SLE and are part of its classification criteria. In addition, we observed that positive titers correlate with disease activity. The presence of anti-Smith antibodies is influenced by ethnicity being most common among Black patients. However, the data regarding their effectiveness as a predictive marker for LN is not fully established. A more sensitive investigation and larger cohorts on diverse ethnic populations could provide a definitive answer regarding the role of anti-Smith antibodies in LN, highlighting the need for additional research.

Central neurological manifestations in a sample of Syrian patients with systemic lupus erythematosus: cross-sectional study.

Introduction: The authors aimed to study systemic lupus erythematosus (SLE) central neurological patterns and their correlations with the disease activity. Patients and methods: The authors' retrospective observational study was carried out on admitted SLE patients. The patients' demographic data, clinical examinations, laboratory tests, imaging studies, and systemic lupus erythematosus disease activity index (SLEDAI) were recorded. Results: Thirty-six SLE patients had neurological manifestations from 203 patients, but 8 patients were excluded. 90.2% were females. The age of neuro-lupus manifestation was 24.1+2.9 years. Neurological manifestations were the initial presentation in 25% of patients. General seizures were the frequent manifestation. SLEDAI was 29.51±18.43, while it was 18.3±9.2 among patients without neuropsychiatric systemic lupus erythematosus (NPSLE). Twenty-five percent of patients had pleocytosis on cerebrospinal fluid (CSF) analysis. Small lesions were seen in 57.1% of patients on brain MRIs, and large lesions were observed in 10.6%. These findings were compatible with the disease activity. Discussion: Central nervous system involvement ranged between 10 and 80%, and much more with active disease. The frequent finding was general seizures. Psychosis and cognitive impairment were relatively frequent. Adult NPSLE manifestations had developed before or around the time of SLE diagnosis and within the first year after diagnosis. These manifestations were directly correlated to the disease activity. Abnormality in CSF is characterized by slight pleocytosis, and elevation of protein with normal fructose. MRI is the neuroimaging test of choice for NPSLE in clinical practice. Conclusion: Central neurological involvement in SLE was seen early in the course of the disease, and correlating to the disease activity.

The vascular endothelial growth factor as a candidate biomarker of systemic lupus erythematosus: a GRADE-assessed systematic review and meta-analysis.

There is an ongoing search for novel biomarkers of endothelial damage, active disease, and organ dysfunction in systemic lupus erythematosus (SLE). We investigated the role of the vascular endothelial growth factor (VEGF) as a candidate biomarker by conducting a systematic review and meta-analysis of studies examining VEGF concentrations in SLE patients and healthy controls. We searched electronic databases (PubMed, Scopus, and Web of Science) from inception to 31 May 2024 (inclusion criteria: VEGF measurement in SLE patients and healthy controls and SLE patients with and without active disease or specific organ dysfunction in case-control studies, recruitment of adult participants, and availability of the full text in the English language; exclusion criteria: non-case-control studies, participants under 18 years, articles reporting duplicate or irrelevant data, and animal studies). We assessed the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively (PROSPERO registration number: CRD42024561636). Circulating VEGF concentrations were significantly higher in SLE patients than in controls (22 studies; standardised mean difference, SMD = 0.71, 95% CI 0.44 to 0.98, p < 0.001; low certainty of evidence). In SLE patients, VEGF concentrations were significantly higher in those with active disease (six studies; SMD = 1.10, 95% CI 0.27 to 1.92, p = 0.009; very low certainty of evidence) and lupus nephritis (four studies; SMD = 0.80, 95% CI 0.03 to 1.57, p = 0.042; very low certainty of evidence). Only one study reported VEGF concentrations in SLE patients with and without pulmonary arterial hypertension. The effect size of the differences in VEGF concentrations between SLE patients and controls was not associated with disease duration, use of glucocorticoids and immunosuppressors, biological matrix assessed, or analytical method used. However, it was significantly associated with the study's geographical location. The evidence was limited by the high but partially explainable heterogeneity and the presence of publication bias which was addressed with the "trim-and-fill" method (SLE presence), the high but partially explainable heterogeneity and lack of assessment of publication bias because of the limited study number (active disease), and the limited study number preventing the identification of sources of heterogeneity, sensitivity analysis, and assessment of publication bias (lupus nephritis). Our results highlight VEGF's potential role as a SLE biomarker and the need for further research, also given the aforementioned limitations, investigating VEGF concentrations in a wide range of SLE patient subgroups.

Clinical and Immunological Profile of Pediatric-Onset Systemic Lupus Erythematosus in Eastern India: A Prospective Observational Study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a strong female predisposition. pSLE often results in a worse prognosis compared to adult SLE. Studies on pSLE from the Indian subcontinent are scarce. OBJECTIVE: This study aims to describe the clinical manifestations, laboratory and serological parameters, management, and outcomes of pSLE patients from a premier tertiary care institute in Eastern India. METHODS: This prospective observational study was conducted at Kalinga Institute of Medical Sciences, Bhubaneswar, from September 2020 to October 2023. Children aged 1-14 years fulfilling the Systemic Lupus International Collaborating Clinics criteria for SLE were included. A detailed history, clinical examination, and laboratory investigations were performed. Data on complications, treatment, and outcomes were collected. Statistical analysis was done using SPSS Statistics version 21 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.). RESULTS: Out of 114,009 patients (outdoor and indoor), 40 were diagnosed with pSLE, resulting in an incidence of 0.35 per 1000 children. The female-to-male ratio was 7:1. The mean age of presentation was 11.67 ± 2.37 years. Among the predominant symptoms observed, mucocutaneous manifestations were seen in 39 (97.5%), followed by pallor in 36 (90%), and fever in 33 (82.5%). The most common organ system involved was mucocutaneous, observed in 39 (97.5%) patients, followed by hematological in 36 (90%) and renal in 19 (47.5%). Lupus nephritis was observed in 19 (47.5%) patients, with class IV being the most common. Anti-nuclear antibody and anti-double-stranded DNA were positive in 39 (97.5%) and 27 (68%) of children, respectively. Complete remission was achieved in 14 (35%), improvement in 16 (40%), and flare-ups in 3 (7.5%) patients. CONCLUSION: pSLE is an uncommon but severe autoimmune disease with significant multi-system involvement. Early identification and prompt treatment are crucial to minimizing adverse outcomes. This study provides detailed insights into the clinical and immunological profile of pSLE in Eastern India, underscoring the need for larger multicentric studies with long-term follow-ups.

High risk of misclassification of acute Parvovirus B19 infection into a systemic rheumatic disease.

Objectives: Parvovirus B19 most frequently causes epidemics of erythema infectiosum in children but also affects adults often leading to rheumatologic manifestations. While the serum profile allows the diagnosis, manifestations may mimic autoimmune conditions. The aim was to evaluate the proportion of patients with acute Parvovirus B19 infection fulfilling classification criteria for rheumatic diseases (RA and SLE). Methods: We evaluated the clinical and serological features of 54 patients diagnosed with acute Parvovirus B19 infection seeking rheumatological attention between March and June 2024. Results: The majority of patients were females (78%), with a mean (s.d.) age of 45 (13) years and 54% could not recall any known exposure. Fifty-one/54 (94%) had arthralgia, 27 (50%) arthritis (oligoarthritis in 67% of them), 24 (44%) fever, 19 (35%) skin rash and 7 (13%) purpura. Symptoms resolution generally occurred within 6 weeks. Complement levels were low in 14/33 (42%) tested patients, while the presence of serum ANA, anti-dsDNA, anti-phospholipids and rheumatoid factor was detected in 21/38 (55%), 10/26 (38%), 6/12 (50%) and 5/37 (13%) patients, respectively. Classification criteria for SLE were fulfilled in 93% of ANA-positive patients and RA criteria in 38% of patients with arthritis. Conclusions: Parvovirus B19 infection manifestations may vary and nearly all patients with positive serum ANA fulfil the classification criteria for SLE. The risk of misclassification in patients with viral infection should not be overlooked.

B cell function in patients with systemic lupus erythematosus is regulated by the upregulation of JunD.

Purpose: Systemic lupus erythematosus (SLE) is largely caused by B cell dysfunction. JunD is an activator protein 1 family protein that has been linked to the regulation of apoptotic and proliferative activities. However, the precise mechanism(s) by which JunD functions remains to be fully elucidated. Accordingly, this study aimed to clarify the functional importance of JUND gene expression in SLE, with further analyses of the functional role that JunD plays as a regulator of B cell proliferation and immune function. Methods: Reverse transcriptase quantitative polymerase chain reaction techniques were used to analyze JunD expression in B cells of patients with SLE and healthy subjects. Cell Counting Kit-8 (CCK-8) assays and flow cytometry methods were used to characterise proliferative activity, cell cycle progression, and apoptosis of B cells in which JunD was either knocked down or overexpressed. The immune status and autophagic activity of these cells were assessed using Western immunoblotting and enzyme-linked immunosorbent assay (ELISA). Additionally, a JunD knockdown mouse model was established, and the functional role of B cell JunD expression in the pathogenesis of SLE was assessed using Western immunoblotting, ELISA, and haematoxylin and eosin staining. Results: B cells from patients with SLE exhibited upregulation of JunD, with overexpression facilitating in vitro cellular proliferation and modulation of the immune and autophagic status of these B cells. JunD knockdown was also sufficient to modulate in vivo immune function and the autophagic status of B cells. Conclusion: JunD was upregulated in the B cells of patients with SLE, where it regulates proliferation, autophagy, and immunity.

Relationship between clinical manifestations and serological profile in patients affected by Systemic Lupus Erythematosus.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by a variety of both signs and symptoms; it mainly affects women of childbearing age, with an estimated prevalence of 24/100,000 people in Europe and North America. SLE is often described as an antibodies-driven disease as its clinical manifestations are usually associated with the presence or the absence of specific antibodies. Objectives: To evaluate clinical manifestations in patients with SLE and to assess the relationship with the presence of specific antibodies by using real-world data. Methods: A retrospective study was performed; the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus were used to classify patients with SLE. Data concerning serological profiles (which included Antinuclear antibodies - ANA, anti dsDNA, anti-Ro/SS-A, anti-La/SS-B, anti-Smith) were gathered along with medical records of clinical manifestations. Complement levels were also tested for possible clinical correlations. χ² or Fisher's exact tests were utilized to establish associations between autoantibodies and symptoms. The odds ratios (OR) and their 95% confidence intervals (CI) were computed. No correction was made for multiple testing; only a p-value 0.01 ≤ was considered significant. Results: One-hundred and twenty-seven patients (n=127, mean age 53.43 ± 14.02) were enrolled in this study. Anti-dsDNA antibodies were found to be statistically significant for both malar rash and proteinuria; anti-Ro/SSA antibodies showed an association with photosensitivity and pericarditis; furthermore, a strong association was found between anti-Ro antibodies and proteinuria, but only if anti-dsDNA antibodies were present as well. Patients who tested positive for anti-La/SSB antibodies correlated with a threefold increase in the risk of developing pericarditis. Lastly, anti-Smith appeared to be associated with NPSLE as well as an increased risk for both autoimmune hemolytic anemia and thrombocytopenia. Conclusions: In our study, many associations confirmed those found in previous studies; however, new relationships between antibodies and clinical manifestations were found thus indicating the need for additional evaluations to assess these correlations further.

Case Report: p40 phox deficiency underlying pediatric-onset systemic lupus erythematosus.

Introduction: Systemic lupus erythematosus is a multi-faceted autoimmune disorder of complex etiology. Pre-pubertal onset of pediatric systemic lupus erythematosus (pSLE) is uncommon and should raise suspicion for a genetic driver of disease. Autosomal recessive p40 phox deficiency is a rare immunologic disorder characterized by defective but not abolished NADPH oxidase activity with residual production of reactive oxygen species (ROS) by phagocytic cells. Case presentation: We report the case of a now 18-year-old female with pSLE onset at 7 years of age. She presented with recurrent fever and malar rash. Aspects of her immune dysregulation over time have included typical pSLE features including production of autoantibodies, hematologic manifestations, and hypocomplementemia, as well as chronic suppurative skin lesions and recurrent infections. Genetic analysis revealed biallelic pathogenic variants in NCF4 resulting in p40 phox deficiency. Comprehensive NADPH oxidase activity studies confirmed significantly decreased production of reactive oxygen species, confirming the cellular phenotype seen in p40 phox deficient patients. Conclusions: Here, we present a patient with pSLE harboring biallelic variants in NCF4. Our patient represents a unique clinical presentation of severe onset autoimmunity in the setting of a rare inborn error of immunity affecting NADPH oxidase activity. This case underscores the need to consider genetic causes of pSLE in cases of pre-pubertal onset and atypical disease.

Epidural blood patching in an anticoagulated patient with intracranial hypotension.

A middle-aged man had classical clinical and radiographical features of spontaneous intracranial hypotension, refractory to conservative management. His medical history included antiphospholipid syndrome, autoimmune thrombocytopenia and recurrent thrombotic events. To reduce his risk from epidural blood patching, we stopped his anticoagulation, but he developed thrombosis. Despite therapeutic challenges, we performed a fluoroscopically guided epidural blood patch successfully at multiple levels, with significant symptom and radiological improvement maintained at 9 months. We review the place of epidural blood patching in people with spontaneous intracranial hypotension who either take anticoagulants or have coexisting blood disorders.

Association Study of 3-untranslated region Haplotype of Human leukocyte antigen-G Gene with Lupus.

Background: Human leukocyte antigen-G (HLA-G) is a pivotal protein involved in immune regulation and tolerance, while systemic lupus erythematosus (SLE) is a multifaceted autoimmune condition influenced by genetic and environmental factors. Research indicates that variations and mutations in HLA-G may impact SLE development. Objective: This study aimed to explore the relationship between polymorphisms in the 3'-untranslated region (UTR) of the HLA-G gene and SLE. Methods: DNA from 100 SLE patients and 100 controls was analyzed using polymerase chain reaction to amplify the target sequence. Allele and genotype frequencies were determined, and haplotypes were assessed using Haploview v.4.2 software, with linkage disequilibrium calculated. Results: Findings revealed that the +2960 Ins allele was significantly linked to SLE as a risk factor, with the Del allele showing a protective effect. In addition, the +3010C allele and +3187A allele were significantly associated with SLE at both allele and genotype levels. The +3142 GG homozygote was notably linked to SLE at the genotype level. Haplotype analysis identified UTR-2 haplotypes as risk factors for SLE, whereas the UTR-1 haplotype was protective, shedding light on genetic factors influencing SLE risk. Conclusion: This study underscores the importance of HLA-G gene 3'-UTR polymorphisms in SLE susceptibility, suggesting their potential as diagnostic or therapeutic targets.

Hypertrophic Cardiomyopathy Requiring Myectomy in a Young Patient With Systemic Lupus Erythematosus: A Case Report.

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect multiple organ systems. Among these, the heart, including the pericardium, conduction system, myocardium, valves, and coronary arteries, can be affected. Hypertrophic cardiomyopathy (HCM) is a myocardial disease caused mainly by genetic mutation. The association between SLE and HCM is still unclear. We are reporting a case of a 25-year-old female with SLE with end-stage renal disease (ESRD) due to lupus nephritis, who was found to have hypertrophic obstructive cardiomyopathy (HOCM) on the echocardiogram and required septal myectomy. She presented to the hospital with dyspnea and was admitted as a hypertensive emergency with pulmonary edema, which required intubation and admission to the cardiac intensive care unit (CICU). She underwent urgent hemodialysis and blood pressure medication adjustment and then improved and was discharged home. Based on the literature review, 10 cases of SLE and HCM were reported, and the underlying mechanisms linking SLE and HCM remain unclear. Further studies are warranted for a better understanding of the association between SLE and HCM.

Reduced TRIM expression correlates with anomalous CD4 T cell activation in systemic lupus Erythematosus and its clinical diagnostic potential.

OBJECTIVE: This study seeks to elucidate the expression, function, and clinical relevance of the T cell receptor interacting molecule (TRIM) within circulating CD4+T cell subsets in systemic lupus erythematosus (SLE) patients. METHODS: We assessed TRIM expression across distinct subpopulations of human peripheral blood mononuclear cells (PBMCs) through the analysis of publicly available single-cell RNA sequencing data. In addition, TRIM expression was investigated within CD4+T cell subsets of peripheral blood and spleens in mice. PBMCs were isolated from both SLE patients, healthy controls (HCs) and rheumatoid arthritis (RA) patients with subsequent measurement and comparative analysis of TRIM expression and functional molecules using flow cytometry. To gauge the clinical relevance of TRIM in SLE, correlation and ROC curve analyses were performed. RESULTS: In both healthy humans and mice, TRIM was higher expressed within CD4+T cell subsets, especially in naive CD4+T cells. TRIM+ Tregs exhibited lower Helios+ cells and CD45RA-FoxP3hi cells percentages compared to TRIM- Treg cells. TRIM+T cells demonstrated reduced granzyme B and perforin secretion and increased IFN-γ secretion in comparison to TRIM- T cells. Notably, the proportion of TRIM+CD4+T cells was diminished in SLE patients. The downregulation of TRIM+ in CD4+T cells positively correlated with diminished complement C3 and C1q levels and inversely correlated with CRP. The identification of TRIM-associated CD4 T cell subsets aids in distinguishing SLE patients from HCs and those with RA. CONCLUSIONS: Reduced TRIM expression is linked to abnormal CD4+T cell activation in SLE. TRIM-associated CD4+T cells may be implicated in the pathogenesis of SLE and hold potential for clinical diagnostic purposes.

Monoclonal Gammopathy of Renal Significance With Preexisting Connective Tissue Disease: A Case Report.

Monoclonal gammopathy of renal significance (MGRS) has lately drawn the interest of physicians and pathologists due to the ability of these monoclonal proteins to cause end-organ damage. The early detection of this monoclonal protein along with hematological studies and renal biopsy are essential to establish the associated nephropathological diagnosis. We herein describe the case of a patient with MGRS and the diagnostic entity involved. She responded well to the treatment as co-managed by a multidisciplinary team of nephrologists, hematologists, and renal pathologists.

Renal vascular lesions in childhood-onset lupus nephritis.

BACKGROUND: This study aimed to determine the clinical significance of renal vascular lesions (RVLs) in childhood-onset lupus nephritis (cLN). METHODS: We retrospectively reviewed all children with biopsy-proven cLN between 2004-2020 to evaluate the prevalence of RVLs on kidney biopsy and its associated factors and long-term outcomes. The composite kidney outcome was defined as advanced chronic kidney disease (CKD) stage 3-5, kidney failure and death. RESULTS: 107 biopsies from 84 Chinese patients were analysed. RVLs were observed in 19 patients (22.6%), including non-inflammatory necrotizing vasculopathy (NNV, n = 6), thrombotic microangiopathy (TMA, n = 4), arterial sclerosis (AS, n = 3), concurrent NNV with AS (n = 4), concurrent NNV with TMA (n = 1) and concurrent true renal vasculitis with AS (n = 1). The presence of RVLs was associated with lower estimated glomerular filtration rate (eGFR) (66.9 ± 40.3 vs. 95.6 ± 39.4 ml/min/1.73m2, p = 0.005), haemoglobin level (9.1 ± 1.9 vs. 10.4 ± 1.9 g/dL, p = 0.008) and platelet count (150.1 ± 96.4 vs. 217.2 ± 104.8 × 109/L, p = 0.01). LN classes and activity/chronicity indices were similar. Patients with RVLs had poorer composite kidney outcomes, though not reaching statistical significance (log-rank test, p = 0.06). The presence of NNV was associated with inferior survival free from composite kidney outcome (log-rank test, p = 0.0018), compared to other forms of RVLs and those without RVLs. Univariate analysis revealed NNV (HR 7.08, 95% CI 1.67-30.03) was predictive of composite kidney outcome. CONCLUSION: RVLs are present in one-fifth of cLN patients and are associated with severe presentation. NNV is associated with worse long-term kidney outcome. Routine evaluation of RVLs is warranted and should be incorporated into future classification criteria.

Case Report: A Case Report on an 18-Year-Old Female with Cerebral Vasculitis in Systemic Lupus Erythematosus (SLE).

Cerebral vasculitis is a rare but severe complication of Systemic Lupus Erythematosus (SLE), presenting significant challenges in management due to its potential for devastating neurological consequences and poor prognosis. We present a case of an 18-year-old female with known SLE who presented with seizures, declining cognitive function, and unresponsiveness. Neurological examination, laboratory investigations, and radiological imaging supported the diagnosis of cerebral vasculitis secondary to SLE. Despite aggressive immunosuppressive therapy, the patient's neurological status continued to deteriorate, leading to respiratory failure and multiorgan dysfunction. Ultimately, the patient succumbed to multiorgan failure attributed to severe CNS vasculitis and its complications. This case underscores the importance of early recognition and aggressive management of cerebral vasculitis in SLE while highlighting the need for further research into more effective therapeutic strategies to improve patient outcomes.

Trends and disparities in cardiovascular deaths in systemic lupus erythematosus: A population-based retrospective study in the United States from 1999 to 2020.

PURPOSE: This study aimed to analyze two decades of consecutive mortality data to investigate cardiovascular deaths in Systemic Lupus Erythematosus (SLE) across the United States (US), identifying patterns and disparities in mortality rates. METHODS: A retrospective analysis was conducted using mortality data from the CDC WONDER database spanning 1999-2020. ICD-10 codes for diseases of circulatory system (I00-I99) and for SLE (M32) were used to identify cardiovascular-related deaths in SLE among adults aged 25 years and older at the time of death. Age-adjusted mortality rates (AAMRs) per 1,000,000 persons were calculated, and trends were assessed using Average Annual Percentage Change (AAPC) and Annual Percent Change (APC) using Joinpoint. Data were stratified by year, sex, race/ethnicity, and geographical regions. RESULTS: Between 1999 and 2020, cardiovascular-related deaths in SLE accounted for 6,548 deaths among adults aged 25 and older in the US. The overall AAMR for cardiovascular-related deaths in SLE decreased from 1.81 in 1999 to 1.53 in 2020, with an AAPC of -1.00 (95% CI: -1.91 to -0.24, p=0.025). A significant decline occurred from 1999 to 2014 with an APC of -3.20 (95% CI: -5.56 to -2.18; p=0.02), followed by a notable increase of 4.73 (95% CI: 0.41 to 18.29, p=0.23) from 2014 to 2020. Women exhibited higher AAMRs compared to men (women: 2.12, men: 0.53). The AAMR decreased for both men and women, with a steeper decline for men from 1999 to 2014 (APC: -4.85 95% CI: -15.58 to -2.62; p<0.02) compared to women in the same period (APC: -2.81 95% CI: -5.78 to -1.73; p<0.03). The Black cohort had a higher AAMR (3.54 95% CI: 3.37 to 3.70), compared to the White cohort (1.12 95% CI: 1.09 to 1.16). The highest mortality was in the Western region (AAMR: 1.60 95% CI: 1.52 to 1.68). Geographically, AAMRs ranged from 0.62 in Massachusetts to 3.11 in Oklahoma. Metropolitan areas had higher AAMRs than Non-metropolitan areas [(1.41 95% CI: 1.37 to 1.45) vs (1.29 95% CI: 1.21 to 1.37)], with a significant mortality reduction in Metropolitan area from 1999-2020 (AAPC: -1.04 95% CI: -1.95 to -0.28, p=0.0064) compared to Non-metropolitan areas in the same time frame (AAPC: -0.86, 95% CI: -2.43 to 0.33 p=0.152). CONCLUSIONS: This analysis highlights notable differences in mortality rates related to cardiovascular deaths in SLE. The target population was adult patients aged 25 and older in the United States. These results are based on demographic and geographic factors. Initially, there was a considerable decrease, but recently the mortality rates have started to rise. This highlights the importance of patient focused interventions to address disparities and improve health outcomes.

Interleukin-2 immunotherapy reveals human regulatory T cell subsets with distinct functional and tissue-homing characteristics.

Due to its stimulatory potential for immunomodulatory CD4+ regulatory T (Treg) cells, low-dose interleukin-2 (IL-2) immunotherapy has gained considerable attention for the treatment of autoimmune diseases. In this investigator-initiated single-arm non-placebo-controlled phase-2 clinical trial of low-dose IL-2 immunotherapy in systemic lupus erythematosus (SLE) patients, we generated a comprehensive atlas of in vivo human immune responses to low-dose IL-2. We performed an in-depth study of circulating and cutaneous immune cells by imaging mass cytometry, high-parameter flow cytometry, transcriptomics, and targeted serum proteomics. Low-dose IL-2 stimulated various circulating immune cells, including Treg cells with a skin-homing phenotype that appeared in the skin of SLE patients in close interaction with endothelial cells. Analysis of surface proteins and transcriptomes revealed different IL-2-driven Treg cell activation programs, including gut-homing CD38+, skin-homing HLA-DR+, and highly proliferative inflammation-homing CD38+ HLA-DR+ Treg cells. Collectively, these data define the distinct human Treg cell subsets that are responsive to IL-2 immunotherapy.