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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.

ObjectiveAccurate identification of lupus nephritis (LN) cases is essential for patient management, research and public health initiatives. However, LN diagnosis codes in electronic health records (EHRs) are underused, hindering efficient identification. We investigated the current performance of International Classification of Diseases (ICD) codes, 9th and 10th editions (ICD9/10), for identifying prevalent LN, and developed scoring systems to increase identification of LN that are adaptable to settings with and without LN ICD codes.MethodsTraining and test sets derived from EHR data from a large health system. An external set comprised data from the EHR of a second large health system. Adults with ICD9/10 codes for SLE were included. LN cases were ascertained through manual chart reviews conducted by rheumatologists. Two definitions of LN were used: strict (definite LN) and inclusive (definite, potential or diagnostic uncertainty). Gradient boosting models including structured EHR fields were used for predictor selection. Two logistic regression-based scoring systems were developed ('LN-Code' included LN ICD codes and 'LN-No Code' did not), calibrated and validated using standard performance metrics.ResultsA total of 4152 patients from University of California San Francisco Medical Center and 370 patients from Zuckerberg San Francisco General Hospital and Trauma Center met the eligibility criteria. Mean age was 50 years, 87% were female. LN diagnosis codes demonstrated low sensitivity (43-73%) but high specificity (92-97%). LN-Code achieved an area under the curve (AUC) of 0.93 and a sensitivity of 0.88 for identifying LN using the inclusive definition. LN-No Code reached an AUC of 0.91 and a sensitivity of 0.95 (0.97 for the strict definition). Both scoring systems had good external validity, calibration and performance across racial and ethnic groups.ConclusionsThis study quantified the underutilisation of LN diagnosis codes in EHRs and introduced two adaptable s

This study focuses on understanding the transcriptional heterogeneity of activated platelets and its impact on diseases such as sepsis, COVID-19, and systemic lupus erythematosus (SLE). Recognizing the limited knowledge in this area, our research aims to dissect the complex transcriptional profiles of activated platelets to aid in developing targeted therapies for abnormal and pathogenic platelet subtypes. We analyzed single-cell transcriptional profiles from 47,977 platelets derived from 413 samples of patients with these diseases, utilizing Deep Neural Network (DNN) and eXtreme Gradient Boosting (XGB) to distinguish transcriptomic signatures predictive of fatal or survival outcomes. Our approach included source data annotations and platelet markers, along with SingleR and Seurat for comprehensive profiling. Additionally, we employed Uniform Manifold Approximation and Projection (UMAP) for effective dimensionality reduction and visualization, aiding in the identification of various platelet subtypes and their relation to disease severity and patient outcomes. Our results highlighted distinct platelet subpopulations that correlate with disease severity, revealing that changes in platelet transcription patterns can intensify endotheliopathy, increasing the risk of coagulation in fatal cases. Moreover, these changes may impact lymphocyte function, indicating a more extensive role for platelets in inflammatory and immune responses. This study identifies crucial biomarkers of platelet heterogeneity in serious health conditions, paving the way for innovative therapeutic approaches targeting platelet activation, which could improve patient outcomes in diseases characterized by altered platelet function.

Mitochondria are eukaryotic cellular organelles that function in energy metabolism, ROS production, and programmed cell death. Cutaneous epithelial and hair follicle dermal papilla cells are energy-rich cells that thereby may be affected by mitochondrial dysfunction and DNA mutation accumulation. In this review, we aimed to summarize the medical literature assessing dermatologic conditions and outcomes associated with mitochondrial dysfunction. A search of PubMed and Embase was performed with subsequent handsearching to retrieve additional relevant articles. Mitochondrial DNA (mtDNA) deletions, mutation accumulation, and damage are associated with phenotypic signs of cutaneous aging, hair loss, and impaired wound healing. In addition, several dermatologic conditions are associated with aberrant mitochondrial activity, such as systemic lupus erythematosus, psoriasis, vitiligo, and atopic dermatitis. Mouse model studies have better established causality between mitochondrial damage and dermatologic outcomes, with some depicting reversibility upon restoration of mitochondrial function. Mitochondrial function mediates a variety of dermatologic conditions, and mitochondrial components may be a promising target for therapeutic strategies.

BackgroundSocial determinants of health are consistently associated with systemic lupus erythematosus (SLE) outcomes. However, social determinants of health are typically measured with conventional socioeconomic status factors such as income or education. We assessed the association of economic insecurities (ie, food, housing, health care, and financial insecurity) with patient-reported outcomes in a cohort of patients with SLE.MethodsIn this cross-sectional analysis, data were derived from the California Lupus Epidemiology Study based in the San Francisco Bay Area, CA, USA. Participants were recruited between Feb 25, 2015, and Jan 10, 2018, from rheumatology clinics. Inclusion criteria were Bay Area residency; oral fluency in English, Spanish, Cantonese, or Mandarin; 18 years or older; ability to provide informed consent; and a physician confirmed SLE diagnosis. Food, housing, health care, and financial economic insecurities were assessed by validated screening tools. Patient-reported outcomes were obtained using PROMIS, Quality of Life in Neurological Disorders (known as Neuro-QoL) Cognitive Function short form, Patient Health Questionnaire (PHQ)-8, and General Anxiety Disorder (GAD)-7 instruments. Poverty was defined as household income of 125% or less of the federal poverty limit. Lower education was defined as less than college-graduate education. The association of economic insecurities with patient-reported outcomes was assessed by multivariable linear regression models adjusting for demographics, SLE disease characteristics, and comorbidities. We tested for interactions of insecurities with poverty and education.FindingsThe final cohort included 252 participants. Mean age was 49·7 (SD 13·4) years, 228 (90%) of 252 were women and 24 (10%) were men. 80 (32%) individuals self-identified as Asian, 26 (10%) as Black, 101 (40%) as White, eight (3%) as mixed race, and 37 (15%) as other race; 59 (23%) self-identified as Hispanic. 135 (54%) individuals had at least o

Masalah utama dalam melakukan pengobatan lupus adalah kebanyakan obat untuk terapi yang diberikan belum mendapat pengesahan sehingga masih termasuk dalam golongan obat off label untuk pengobatan lupus. Penggunaan obat off label dapat membawa potensi kejadian efek samping pada pasien Lupus yang berdampak peningkatan biaya kesehatan. Penelitian ini bertujuan untuk mengetahui gambaran biaya kesehatan pada pasien lupus yang menggunakan obat off label pada terapinya, sebagai evaluasi terpadu dalam mengupayakan peningkatan kualitas hidup dan menjamin perawatan yang tepat pada pasien Lupus. Penelitian ini menggunakan desain penelitian observasional deskriptif dengan menggunakan cara survey untuk melihat kejadian efek samping penggunaan obat-obatan off label pada pasien lupus. Penelitian ini merupakan penelitian prospektif yang dilakukan dengan mengobservasi pasien lupus untuk mengetahui biaya kesehatan yang dikeluarkan dalam terapi yang menggunakan obat off label. Hasil penelitian didapatkan responden terbanyak berada pada usia dewasa (19 responden atau 47,5%), kemudian responden terbanyak adalah perempuan (37 responden atau 92,5%).  Hasil penelitian ini menunjukkan dengan jelas bahwa gambaran biaya Kesehatan dalam penggunaan obat off label pengobatan penyakit Lupus yang paling tinggi yaitu 2 kombinasi obat off label Metylprednisolon dan Imuran sebesar Rp.313.285. Kemudian biaya terendah yaitu penggunaan monoterapi metylprednisolon sebesar Rp.5.833.

Masalah utama dalam melakukan pengobatan lupus adalah kebanyakan obat untuk terapi yang diberikan belum mendapat pengesahan sehingga masih termasuk dalam golongan obat off label untuk pengobatan lupus. Penggunaan obat off label dapat membawa potensi kejadian efek samping pada pasien Lupus yang berdampak peningkatan biaya kesehatan. Penelitian ini bertujuan untuk mengetahui gambaran biaya kesehatan pada pasien lupus yang menggunakan obat off label pada terapinya, sebagai evaluasi terpadu dalam mengupayakan peningkatan kualitas hidup dan menjamin perawatan yang tepat pada pasien Lupus. Penelitian ini menggunakan desain penelitian observasional deskriptif dengan menggunakan cara survey untuk melihat kejadian efek samping penggunaan obat-obatan off label pada pasien lupus. Penelitian ini merupakan penelitian prospektif yang dilakukan dengan mengobservasi pasien lupus untuk mengetahui biaya kesehatan yang dikeluarkan dalam terapi yang menggunakan obat off label. Hasil penelitian didapatkan responden terbanyak berada pada usia dewasa (19 responden atau 47,5%), kemudian responden terbanyak adalah perempuan (37 responden atau 92,5%).  Hasil penelitian ini menunjukkan dengan jelas bahwa gambaran biaya Kesehatan dalam penggunaan obat off label pengobatan penyakit Lupus yang paling tinggi yaitu 2 kombinasi obat off label Metylprednisolon dan Imuran sebesar Rp.313.285. Kemudian biaya terendah yaitu penggunaan monoterapi metylprednisolon sebesar Rp.5.833.

Background: Lupus nephritis (LN) occurs in ~50% of patients with SLE and is the most common, but not the only, cause of kidney injury in SLE. Men with SLE tend to have more aggressive disease with higher rates of renal and cardiovascular involvement and are more likely to develop kidney failure than women. Methods: This systematic review focused on full-text English literature published between 2014 and 2024 using the PRISMA 2020 guidelines. Editorials and review pieces published in the same journal as the submission without a DOI were not accepted. The literature was compiled using PubMed, ScienceDirect, and SagePub, among other online venues. Result: Five publications were found to be directly related to our ongoing systematic examination after a rigorous three-level screening approach. Subsequently, a comprehensive analysis of the complete text was conducted, and additional scrutiny was given to these articles. Conclusion: Achieving a complete clinical response to treatment is critical to preserving long-term kidney health.

Background: Lupus nephritis (LN) occurs in ~50% of patients with SLE and is the most common, but not the only, cause of kidney injury in SLE. Men with SLE tend to have more aggressive disease with higher rates of renal and cardiovascular involvement and are more likely to develop kidney failure than women. Methods: This systematic review focused on full-text English literature published between 2014 and 2024 using the PRISMA 2020 guidelines. Editorials and review pieces published in the same journal as the submission without a DOI were not accepted. The literature was compiled using PubMed, ScienceDirect, and SagePub, among other online venues. Result: Five publications were found to be directly related to our ongoing systematic examination after a rigorous three-level screening approach. Subsequently, a comprehensive analysis of the complete text was conducted, and additional scrutiny was given to these articles. Conclusion: Achieving a complete clinical response to treatment is critical to preserving long-term kidney health.

ObjectiveStudies have suggested a potential link between traumatic experiences, psychological stress, and autoimmunity, but the impact of stress on disease activity and symptom severity in systemic lupus erythematosus (SLE) remains unclear. The present study was undertaken to examine whether increases in perceived stress independently associate with worse SLE disease outcomes over 3 years of follow-up.MethodsParticipants were drawn from the California Lupus Epidemiology Study (CLUES). Stress was measured annually using the 4-item Perceived Stress Scale (PSS). Participants with increases of ≥0.5 SD in PSS score were defined as having an increase in stress. Four outcomes were measured at the year 3 follow-up visit: physician-assessed disease activity (Systemic Lupus Erythematosus Disease Activity Index); patient-reported disease activity (Systemic Lupus Activity Questionnaire); pain (Patient-Reported Outcomes Measurement Information System [PROMIS] pain interference scale); and fatigue (PROMIS fatigue scale). Multivariable linear regression evaluated longitudinal associations of increase in stress with all 4 outcomes while controlling for potential confounders.ResultsThe sample (n = 260) was 91% female, 36% Asian, 30% White, 22% Hispanic, and 11% African American; the mean ± SD age was 46 ± 14 years. In adjusted longitudinal analyses, increase in stress was independently associated with greater physician-assessed disease activity (P = 0.015), greater self-reported disease activity (P < 0.001), more pain (P = 0.019), and more fatigue (P < 0.001).ConclusionIn a racially diverse sample of individuals with SLE, those who experienced an increase in stress had significantly worse disease activity and greater symptom burden at follow-up compared to those with stress levels that remained stable or declined. Findings underscore the need for interventions to bolster stress resilience and support effective coping strategies among individuals l

ObjectiveTo explore long-term safety and tolerability of anifrolumab 300 mg compared with placebo in patients with systemic lupus erythematosus (SLE) who completed a Treatment of Uncontrolled Lupus via the Interferon Pathway (TULIP) trial and enrolled in the placebo-controlled 3-year long-term extension (LTE) study (ClinicalTrials.gov identifier: NCT02794285).MethodsIn the blinded LTE study, patients continued anifrolumab 300 mg, switched from anifrolumab 150 mg to 300 mg, or were re-randomized from placebo to receive either anifrolumab 300 mg or to continue placebo, administered every 4 weeks. Primary comparisons in the LTE study were between patients who received anifrolumab 300 mg or placebo throughout the TULIP and LTE studies. For rare safety events, comparisons included patients who received any anifrolumab dose during TULIP or LTE. When exposure differed, exposure-adjusted incidence rates (EAIRs) per 100 patient-years were calculated.ResultsIn the LTE study, EAIRs of serious adverse events (SAEs) were 8.5 with anifrolumab compared with 11.2 with placebo; likewise, EAIRs of AEs leading to treatment discontinuation were 2.5 versus 3.2, respectively. EAIRs of non-opportunistic serious infections were comparable between groups (3.7 with anifrolumab versus 3.6 with placebo). Exposure-adjusted event rates of COVID-related AEs, including asymptomatic infections, were 15.5 with anifrolumab compared with 9.8 with placebo. No COVID-related AEs occurred in fully vaccinated individuals. EAIRs of malignancy and major acute cardiovascular events were low and comparable between groups. Anifrolumab was associated with lower cumulative glucocorticoid use and greater mean improvement in the SLE Disease Activity Index 2000, compared with placebo.ConclusionThis LTE study represents the longest placebo-controlled clinical trial performed in SLE to date. No new safety findings were identified in the LTE study, supporting the favorable benefit-risk profile of anifrolumab for patien

Neonatal lupus (NLE) is a rare acquired autoimmune disorder caused by transplacental passage of maternal autoantibodies to Sjogren's Syndrome A or B (SSA-SSB) autoantigens (Vanoni et al. in Clin Rev Allerg Immunol 53:469-476, 2017) which target fetal and neonatal tissues for immune destruction. The cardiac trademark of NLE is autoimmune heart block, which accounts for more than 80% of cases of complete atrioventricular heart block (AVB) in newborns with a structurally normal heart (Martin in Cardiol Young 24: 41-46, 2014). NLE presenting with cardiac alterations not involving rhythm disturbances are described in the literature, but they are rare. Here, we report a case of a neonate with high anti-SSA antibodies who developed severe ventricular dysfunction in the absence of rhythm abnormalities, endocardial fibroelastosis, and dilated cardiomyopathy (Trucco et al. in J Am Coll Cardiol 57:715-723, https://doi.org/10.1016/j.jacc.2010.09.044 , 2011), the most common cardiac presentations of NLE. The patient developed severe multiorgan dysfunction syndrome that required prolonged critical care support but fully recovered and was discharged home. We highlight the unusual clinical features of this NLE case and the importance of timely treatment of NLE allowing complete recovery of a critically ill neonate.

ObjectivesWe compared the outcomes of patients with or without systemic lupus erythematosus (SLE) who were diagnosed with coronavirus disease 19 (COVID-19) and evaluated factors within patients with SLE associated with severe outcomes.MethodsThis retrospective cohort study used the deidentified Optum COVID-19 electronic health record dataset to identify patients with COVID-19 from 1/1/2020 to 31/12/2020. Cases with SLE were matched with general controls at a ratio of 1:10 by age, sex, race and ethnicity and COVID-19 diagnosis date. Outcomes included 30-day mortality, mechanical ventilation, hospitalisation and intensive care unit admission. We evaluated the relationship between COVID-19-related outcomes and SLE using multivariable logistic regression. In addition, within SLE cases, we examined factors associated with COVID-19 related outcomes, including disease activity and SLE therapy.ResultsWe included 687 patients matched with 6870 controls. Unadjusted rates of outcomes for patients with SLE were significantly worse than for matched controls including mortality (3.6% vs 1.8%), mechanical ventilation (6% vs 2.5%) and hospitalisation (31% vs 17.7%) (all p<0.001). After multivariable adjustment, patients with SLE had increased risks of mechanical ventilation (OR 1.81, 95% CI 1.16 to 2.82) and hospitalisation (OR 1.32, 95% CI 1.05 to 1.65). Among patients with SLE, severe disease activity was associated with increased risks of mechanical ventilation (OR 5.83, 95% CI 2.60 to 13.07) and hospitalisation (OR 3.97, 95% CI 2.37 to 6.65). Use of glucocorticoids, mycophenolate and tacrolimus before COVID-19 was associated with worse outcomes.ConclusionPatients with SLE had increased risk of severe COVID-19-related outcomes compared with matched controls. Patients with severe SLE disease activity or prior use of corticosteroids experienced worse outcomes.

IntroductionSignificant heterogeneity still exists in the nomenclature of renal involvement in antiphospholipid syndrome (APS).MethodsWe applied a hierarchical cluster analysis to determine subgroups of patients according to clinical, laboratory, and renal histology characteristics in a cohort of subjects with confirmed antiphospholipid antibodies (aPL) positivity and biopsy proven aPL-related renal injuries. Kidney outcomes were then assessed at 12 months.ResultsA total of 123 aPL-positive patients were included in the study (101 [82%] female, 109 [88.6%] with systemic lupus erythematosus [SLE], 14 (11.4%) with primary APS [PAPS]). Three clusters were identified. Twenty-three patients (18.7%) were included in the first cluster (cluster 1), characterized by a higher prevalence of glomerular capillary and arteriolar thrombi and fragmented red blood cells in the subendothelial space. Cluster 2 included 33 patients (26.8%) and showed a higher prevalence of fibromyointimal proliferative lesions as seen in hyperplastic vasculopathy. Cluster 3 was the largest (67 patients, mainly with SLE) and was characterized by higher prevalence of subendothelial edema, of both glomerular capillaries and arterioles.ConclusionThree different clusters of patients with aPL and renal injuries emerged from our study as follows: the first, with the worst renal prognosis, was associated with features of thrombotic microangiopathy (TMA), thrombosis, triple aPL positivity and higher adjusted Global APS Score (aGAPSS) values; the second, characterized by hyperplastic vasculopathy with an intermediate prognosis, was seen more frequently in patients with cerebrovascular manifestations; and the third, more benign in terms of outcomes and with no overt association with thrombotic features, was characterized by endothelial swelling in concomitant lupus nephritis (LN).

Prolactin (PRL) is elevated in B-cell-mediated lymphoproliferative diseases and promotes B-cell survival. Whether PRL or PRL receptors drive the evolution of B-cell malignancies is unknown. We measure changes in B cells after knocking down the pro-proliferative, anti-apoptotic long isoform of the PRL receptor (LFPRLR) in vivo in systemic lupus erythematosus (SLE)- and B-cell lymphoma-prone mouse models, and the long plus intermediate isoforms (LF/IFPRLR) in human B-cell malignancies. To knockdown LF/IFPRLRs without suppressing expression of the counteractive short PRLR isoforms (SFPRLRs), we employ splice-modulating DNA oligomers. In SLE-prone mice, LFPRLR knockdown reduces numbers and proliferation of pathogenic B-cell subsets and lowers the risk of B-cell transformation by downregulating expression of activation-induced cytidine deaminase. LFPRLR knockdown in lymphoma-prone mice reduces B-cell numbers and their expression of BCL2 and TCL1. In overt human B-cell malignancies, LF/IFPRLR knockdown reduces B-cell viability and their MYC and BCL2 expression. Unlike normal B cells, human B-cell malignancies secrete autocrine PRL and often express no SFPRLRs. Neutralization of secreted PRL reduces the viability of B-cell malignancies. Knockdown of LF/IFPRLR reduces the growth of human B-cell malignancies in vitro and in vivo. Thus, LF/IFPRLR knockdown is a highly specific approach to block the evolution of B-cell neoplasms.

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of Asian-Ancestry (AsA) disproportionately experience more severe SLE compared to individuals of European-Ancestry (EA), including increased renal involvement and tissue damage. However, the mechanisms underlying elevated severity in the AsA population remain unclear. Here, we utilized available gene expression data and genotype data based on all non-HLA SNP associations in EA and AsA SLE patients detected using the Immunochip genotyping array. We identified 2778 ancestry-specific and 327 trans-ancestry SLE-risk polymorphisms. Genetic associations were examined using connectivity mapping and gene signatures based on predicted biological pathways and were used to interrogate gene expression datasets. SLE-associated pathways in AsA patients included elevated oxidative stress, altered metabolism and mitochondrial dysfunction, whereas SLE-associated pathways in EA patients included a robust interferon response (type I and II) related to enhanced cytosolic nucleic acid sensing and signaling. An independent dataset derived from summary genome-wide association data in an AsA cohort was interrogated and identified similar molecular pathways. Finally, gene expression data from AsA SLE patients corroborated the molecular pathways predicted by SNP associations. Identifying ancestry-related molecular pathways predicted by genetic SLE risk may help to disentangle the population differences in clinical severity that impact AsA and EA individuals with SLE.

IntroductionCare of young adults with SLE (YA-SLE, 18-24 years) is challenging due to major life transitions co-occurring with chronic healthcare needs. Studies have demonstrated poorer outcomes in the post-transition period. Epidemiological studies focused on serious infection-related hospitalisation (SIH) in YA-SLE are lacking.MethodsWe used National Inpatient Sample from 2010 to 2019 to study the epidemiology and outcomes of SIH for five common infections in SLE, namely sepsis, pneumonia, urinary tract infections, skin and soft tissue infections, and opportunistic infections. For time trends, we extended the dataset to cover 2000-2019. The primary outcome was the rate of SIH in YA-SLE compared with adults (25-44 years) with SLE and with young adults without SLE (YA-no SLE).ResultsFrom 2010 to 2019, we identified 1 720 883 hospital admissions with SLE in patients aged ≥18 years. Rates of SIH were similar in young adults and adults with SLE (15.0% vs 14.5%, p=0.12), but considerably higher than in the YA-no SLE group (4.2%, p<0.001). Among SLE with SIH, sepsis followed by pneumonia was the most common diagnosis. Significantly higher proportions of SIH among young adults than adults with SLE were comprised of non-white patients, belonged to the lowest income quartile and had Medicaid. However, only race/ethnicity was associated with SIH among YA-SLE. There was a higher prevalence of comorbid lupus nephritis and pleuritis among young adults compared with adults with SLE and SIH, and both comorbidities were associated with SIH in YA-SLE. Increasing rates of SIH, driven by sepsis, were seen over time.DiscussionYA- SLE had similar rates of SIH to adults with SLE. While hospitalised YA-SLE differed sociodemographically from SLE adults and YA-no SLE, only race/ethnicity was associated with SIH in the YA-SLE group. Lupus nephritis and pleuritis were associated with higher SIH in YA-SLE. Among SLE with SIH, increasing trends of sepsis deserve further study.

ObjectiveDuring the COVID-19 pandemic, many research studies were adapted, including our longitudinal study examining cognitive impairment (CI) in systemic lupus erythematosus (SLE). Cognitive testing was switched from in-person to virtual. This analysis aimed to determine if the administration method (in-person vs. virtual) of the ACR-neuropsychological battery (ACR-NB) affected participant cognitive performance and classification.MethodsData from our multi-visit, SLE CI study included demographic, clinical, and psychiatric characteristics, and the modified ACR-NB. Three analyses were undertaken for cognitive performance: (1) all visits, (2) non-CI group visits only and (3) intra-individual comparisons. A retrospective preferences questionnaire was given to participants who completed the ACR-NB both in-person and virtually.ResultsWe analysed 328 SLE participants who had 801 visits (696 in-person and 105 virtual). Demographic, clinical, and psychiatric characteristics were comparable except for ethnicity, anxiety and disease-related damage. Across all three comparisons, six tests were consistently statistically significantly different. CI classification changed in 11/71 (15%) participants. 45% of participants preferred the virtual administration method and 33% preferred in-person.ConclusionsOf the 19 tests in the ACR-NB, we identified one or more problems with eight (42%) tests when moving from in-person to virtual administration. As the use of virtual cognitive testing will likely increase, these issues need to be addressed - potentially by validating a virtual version of the ACR-NB. Until then, caution must be taken when directly comparing virtual to in-person test results. If future studies use a mixed administration approach, this should be accounted for during analysis.

IntroductionAntiphospholipid syndrome (APS) is an autoimmune disease characterised by thrombosis (arterial, venous or small vessel) or obstetrical events and persistent antiphospholipid antibodies (aPL), according to the Sydney classification criteria. Many studies have performed cluster analyses among patients with primary APS and associated autoimmune disease, but none has focused solely on primary APS. We aimed to perform a cluster analysis among patients with primary APS and asymptomatic aPL carriers without any autoimmune disease, to assess prognostic value.MethodsIn this multicentre French cohort study, we included all patients with persistent APS antibodies (Sydney criteria) measured between January 2012 and January 2019. We excluded all patients with systemic lupus erythematosus or other systemic autoimmune diseases. We performed hierarchical cluster analysis on the factor analysis of mixed data coordinates results with baseline patient characteristics to generate clusters.ResultsWe identified four clusters: cluster 1, comprising 'asymptomatic aPL carriers', with low risk of events during follow-up; cluster 2, the 'male thrombotic phenotype', with older patients and more venous thromboembolic events; cluster 3, the 'female obstetrical phenotype', with obstetrical and thrombotic events; and cluster 4, 'high-risk APS', which included younger patients with more frequent triple positivity, antinuclear antibodies, non-criteria manifestations and arterial events. Regarding survival analyses, asymptomatic aPL carriers relapsed less frequently than the others, but no other differences in terms of relapse rates or deaths were found between clusters.ConclusionsWe identified four clusters among patients with primary APS, one of which was 'high-risk APS'. Clustering-based treatment strategies should be explored in future prospective studies.

ObjectiveIn a study of physical and cognitive functioning among predominantly Black individuals with systemic lupus erythematosus (SLE), we compared remotely administered physical and cognitive performance assessments to those collected in person.MethodsA subset of participants who completed an in-person visit in our parent study from 2021 to 2022 (n = 30) were recruited to complete a second, remote visit within 28 days. Physical performance (measured by a modified Short Physical Performance Battery [SPPB]; range 0-12; subscale ranges 0-4; higher = better performance) and cognitive performance (episodic and working memory adjusted t-scores, measured using NIH Toolbox) were measured at both visits. Mean scores were compared using paired t-tests; intraclass correlation coefficients (ICCs) were obtained from two-way mixed effects models. Linear and logistic models were used to estimate stratified associations between performance measures and related outcomes.ResultsParticipants were primarily female (93.3%) and Black (93.3%). In-person versus remote overall SPPB (8.76 vs. 9.43) and chair stand (1.43 vs. 1.90) scores were statistically significantly lower. t-Scores for episodic memory (47.27 vs. 49.53) and working memory (45.37 vs. 47.90) were lower for in-person versus remote visits. The ICC for overall SPPB indicated good agreement (0.76), whereas the ICCs for episodic (0.49) and working memory (0.57) indicated poor-moderate agreement. Associations between assessments of performance with related outcomes were similar and did not statistically significantly differ by modality of visit.ConclusionTo possibly expand and diversify pools of participants in studies of physical and cognitive performance in SLE, remote administration of assessments should be considered for future research.

Background: Many systemic and urinary tract diseases alter renal structure and function, including changing the composition of urine. While routine urinalysis (physical properties, sediment evaluation, urine chemistry analytes) is useful in screening, it has limitations on separating disease processes, structural changes, and functional abnormalities. Likewise, while many individual ‘biomarkers’ have been used to screen for disease, they have not met with widespread clinical adoption. The recent COVID19 Pandemic and the recognition of post-acute sequelae SARS-CoV-2 infection (PASC) have highlighted the need for rapid, scalable, economical, and accurate screening tools for managing disease. Aims: Validate a Raman spectroscopy-based screening technology for urine analysis that could be used for recognition and quantification of systemic and renal effects of acute and PASC COVID19 disease. Methods: One hundred ten (110) urine specimens were obtained from consented adults diagnosed with COVID19 disease by RT-PCR and/or proximate (household) contact With RT-PCR-confirmed COVID19 disease. Samples were analyzed using Raman chemometric urinalysis, a technology that detects hundreds of discrete chemicals in urine and applies computational comparison-machine learning to detect COVID19-associated molecular patterns (‘fingerprints’). Results: When compared with the urine multimolecular ‘fingerprints’ of healthy individuals and patients with known systemic diseases (diabetes mellitus, lupus) that alter renal structure and function, patients with acute and PASC COVID19 had unique ‘fingerprints’ indicative of alterations in renal function (i.e. – infection altered urine composition). Differences in disease severity (mild to severe) were reflected by different ‘fingerprints’ in urine. Roughly 20% of hospitalized patients developed a degree of renal dysfunction (decrements in eGFR) that were correlated with distinct changes in urine fingerprints. Conclusion: Raman chemometric urinal

Introduction: Biopsy is an important diagnostic technique for the treatment of patients with kidney disease. It is possible to make an etiological diagnosis, in addition to determining the prognosis and the probability of response to treatment. Objective: Determine the main indications and the most frequent histopathological findings in renal biopsies performed in the Department of Adult Nephrology of the Hospital de Clínicas from April 2016 to November 2022. Methods: Observational, retrospective, cross-sectional study. Results: 130 biopsies were performed in the period studied, 50.7% in female patients. The main reasons were: nephrotic syndrome 34.6%, systemic lupus ery- thematosus 31.5% and transplant patients with suspected rejection 18.4%. The following most frequent histopathological diagnoses were obtained according to the different indications: focal and segmental glomerulosclerosis-FSGS (24), stage IV lupus nephritis (24) and graft rejection (16), respectively. 0.7% of patients pre- sented nephrectomy as a complication and retroperitoneal hematoma in an equal percentage. Conclusion: 130 renal biopsies were performed, with no important difference between sexes. The main indications were: nephrotic syndrome, systemic lupus erythematosus and suspected graft rejection, with the most frequent histopathological diagnoses being FSGS, stage IV lupus nephritis and rejection, respectively. Complications occurred in 1.4%., Introducción: La biopsia es una técnica de diagnóstico primordial para el tratamiento del paciente con afectación renal. Es posible realizar un diagnóstico etiológico, determinar el pronóstico y la probabilidad de respuesta al tratamiento. Objetivo: Determinar las principales indicaciones y los hallazgos histopatológicos más frecuentes en las biopsias renales realizadas en el Departamento de Nefrología Adultos del Hospital de Clínicas desde abril de 2016 a noviembre de 2022. Métodos: Estudio observacional, retrospectivo, corte transversal. Resultados: Se realizaron 130 biopsias en el período estudiado, 50,7% en pacientes de sexo femenino. Los principales motivos fueron: síndrome nefrótico 34,6%, lupus eritematoso sistémico 31,5% y pacientes trasplantados con sospecha de rechazo 18,4%. Se obtuvieron los siguientes diagnósticos histopatológicos más frecuentes según las diferentes indicaciones: glomeruloesclerosis focal y segmentaria-GEFS (24), nefritis lúpica estadio IV (24) y rechazo del injerto (16). El 0,7% de los pacientes presentó como complicación la nefrectomía e igual porcentaje un hematoma retroperitoneal. Conclusión: Se realizaron 130 biopsias renales, no habiendo diferencia importante entre ambos sexos. Las principales indicaciones fueron: síndrome nefrótico, lupus eritematoso sistémico y sospecha de rechazo del injerto, siendo los diagnósticos histopatológicos más frecuentes GEFS, nefritis lúpica estadio IV y rechazo, respectivamente. Se presentaron complicaciones en 1,4%.

Introduction: Biopsy is an important diagnostic technique for the treatment of patients with kidney disease. It is possible to make an etiological diagnosis, in addition to determining the prognosis and the probability of response to treatment. Objective: Determine the main indications and the most frequent histopathological findings in renal biopsies performed in the Department of Adult Nephrology of the Hospital de Clínicas from April 2016 to November 2022. Methods: Observational, retrospective, cross-sectional study. Results: 130 biopsies were performed in the period studied, 50.7% in female patients. The main reasons were: nephrotic syndrome 34.6%, systemic lupus ery- thematosus 31.5% and transplant patients with suspected rejection 18.4%. The following most frequent histopathological diagnoses were obtained according to the different indications: focal and segmental glomerulosclerosis-FSGS (24), stage IV lupus nephritis (24) and graft rejection (16), respectively. 0.7% of patients pre- sented nephrectomy as a complication and retroperitoneal hematoma in an equal percentage. Conclusion: 130 renal biopsies were performed, with no important difference between sexes. The main indications were: nephrotic syndrome, systemic lupus erythematosus and suspected graft rejection, with the most frequent histopathological diagnoses being FSGS, stage IV lupus nephritis and rejection, respectively. Complications occurred in 1.4%., Introducción: La biopsia es una técnica de diagnóstico primordial para el tratamiento del paciente con afectación renal. Es posible realizar un diagnóstico etiológico, determinar el pronóstico y la probabilidad de respuesta al tratamiento. Objetivo: Determinar las principales indicaciones y los hallazgos histopatológicos más frecuentes en las biopsias renales realizadas en el Departamento de Nefrología Adultos del Hospital de Clínicas desde abril de 2016 a noviembre de 2022. Métodos: Estudio observacional, retrospectivo, corte transversal. Resultados: Se realizaron 130 biopsias en el período estudiado, 50,7% en pacientes de sexo femenino. Los principales motivos fueron: síndrome nefrótico 34,6%, lupus eritematoso sistémico 31,5% y pacientes trasplantados con sospecha de rechazo 18,4%. Se obtuvieron los siguientes diagnósticos histopatológicos más frecuentes según las diferentes indicaciones: glomeruloesclerosis focal y segmentaria-GEFS (24), nefritis lúpica estadio IV (24) y rechazo del injerto (16). El 0,7% de los pacientes presentó como complicación la nefrectomía e igual porcentaje un hematoma retroperitoneal. Conclusión: Se realizaron 130 biopsias renales, no habiendo diferencia importante entre ambos sexos. Las principales indicaciones fueron: síndrome nefrótico, lupus eritematoso sistémico y sospecha de rechazo del injerto, siendo los diagnósticos histopatológicos más frecuentes GEFS, nefritis lúpica estadio IV y rechazo, respectivamente. Se presentaron complicaciones en 1,4%.

Systemic Lupus Erythematosus (SLE) is a chronic systemic autoimmune disease of high clinical and molecular heterogeneity, and a relapsing-remitting pattern. The disease is currently without cure and more prevalent in women. B cell tolerance and production of autoantibodies are critical mechanisms that drive SLE pathophysiology. However, how the balance of the immune system is broken and how the innate and adaptive immune systems are interacting during lupus-specific autoimmune responses are still largely unknown. Here, we review the latest knowledge on B cell development, maturation, and central versus peripheral tolerance in connection to SLE and treatment options. We also discuss the regulation of B cells by conventional T cells, granulocytes, and unconventional T cells, and how effector B cells exert their functions in SLE. We also discuss mechanisms of action of B cell-targeted therapies, as well as possible future directions based on current knowledge of B cell biology., This research was funded by: the Swedish Rheumatism Association, grant number R-969696; King Gustaf V's 80-year Foundation, grant number FAI-2020-0741; Swedish Society of Medicine, grant number SLS-974449; Nyckelfonden, grant number OLL-974804; Professor Nanna Svartz Foundation, grant number 2021-00436; Ulla and Roland Gustafsson Foundation, grant number 2021-26; Region Stockholm, grant number FoUI-955483; Swedish Research Council; Wennergren Foundation; the National Natural Science Foundation of China, grant number 82003364; the Hunan Provincial Natural Science Foundation of China, grant number 2023JJ40827; the Scientific Research Launch Project for new employees of the Second Xiangya Hospital of Central South University; and Karolinska Institutet.

Background: Many systemic and urinary tract diseases alter renal structure and function, including changing the composition of urine. While routine urinalysis (physical properties, sediment evaluation, urine chemistry analytes) is useful in screening, it has limitations on separating disease processes, structural changes, and functional abnormalities. Likewise, while many individual ‘biomarkers’ have been used to screen for disease, they have not met with widespread clinical adoption. The recent COVID19 Pandemic and the recognition of post-acute sequelae SARS-CoV-2 infection (PASC) have highlighted the need for rapid, scalable, economical, and accurate screening tools for managing disease. Aims: Validate a Raman spectroscopy-based screening technology for urine analysis that could be used for recognition and quantification of systemic and renal effects of acute and PASC COVID19 disease. Methods: One hundred ten (110) urine specimens were obtained from consented adults diagnosed with COVID19 disease by RT-PCR and/or proximate (household) contact With RT-PCR-confirmed COVID19 disease. Samples were analyzed using Raman chemometric urinalysis, a technology that detects hundreds of discrete chemicals in urine and applies computational comparison-machine learning to detect COVID19-associated molecular patterns (‘fingerprints’). Results: When compared with the urine multimolecular ‘fingerprints’ of healthy individuals and patients with known systemic diseases (diabetes mellitus, lupus) that alter renal structure and function, patients with acute and PASC COVID19 had unique ‘fingerprints’ indicative of alterations in renal function (i.e. – infection altered urine composition). Differences in disease severity (mild to severe) were reflected by different ‘fingerprints’ in urine. Roughly 20% of hospitalized patients developed a degree of renal dysfunction (decrements in eGFR) that were correlated with distinct changes in urine fingerprints. Conclusion: Raman chemometric urinal

Determining staining patterns by indirect immunofluorescence of antinuclear antibodies (ANA) is essential to diagnose systemic lupus erythematosus, which has an unknown etiology, and it is considered one of the most heterogeneous autoimmune diseases regarding pathogenic, clinical, and analytical criteria. It is known that the prevalence of systemic lupus erythematosus in America, Asia, and northern Europe affects 40 out of every 100,000 inhabitants, and the population diagnosed with this disease increases every year. The purpose of this study was to determine the frequency of positivity of antinuclear antibodies and their staining patterns by indirect immunofluorescence in patients with systemic lupus erythematosus at José Carrasco Arteaga hospital in 2019-2021. This is a descriptive cross-sectional study. The data was collected using a questionnaire and interpreted through simple and crossed tables featuring percentage and frequencies. Tabulation of data and statistical graphs was carried out using the IBM SPSS, trial version, and Microsoft Excel programs. The results showed a total of 164 patients diagnosed with systemic lupus erythematosus, of which 147 (89.64%) tested positive for antinuclear antibodies (ANA), and the homogeneous pattern was the most frequent, reaching 67 individuals (45.58%). The largest number of cases ranged from 31 to 46 years: 71 patients (43.29%), mostly females: 147 (89.63%). The results also showed that ANA positivity with homogeneous staining patterns and nuclear fine speckled was more frequently present in female patients with systemic lupus erythematosus.

Determining staining patterns by indirect immunofluorescence of antinuclear antibodies (ANA) is essential to diagnose systemic lupus erythematosus, which has an unknown etiology, and it is considered one of the most heterogeneous autoimmune diseases regarding pathogenic, clinical, and analytical criteria. It is known that the prevalence of systemic lupus erythematosus in America, Asia, and northern Europe affects 40 out of every 100,000 inhabitants, and the population diagnosed with this disease increases every year. The purpose of this study was to determine the frequency of positivity of antinuclear antibodies and their staining patterns by indirect immunofluorescence in patients with systemic lupus erythematosus at José Carrasco Arteaga hospital in 2019-2021. This is a descriptive cross-sectional study. The data was collected using a questionnaire and interpreted through simple and crossed tables featuring percentage and frequencies. Tabulation of data and statistical graphs was carried out using the IBM SPSS, trial version, and Microsoft Excel programs. The results showed a total of 164 patients diagnosed with systemic lupus erythematosus, of which 147 (89.64%) tested positive for antinuclear antibodies (ANA), and the homogeneous pattern was the most frequent, reaching 67 individuals (45.58%). The largest number of cases ranged from 31 to 46 years: 71 patients (43.29%), mostly females: 147 (89.63%). The results also showed that ANA positivity with homogeneous staining patterns and nuclear fine speckled was more frequently present in female patients with systemic lupus erythematosus.

ObjectiveWe previously demonstrated the utility of the Automated Neuropsychological Assessment Metrics (ANAM) for screening cognitive impairment (CI) in patients with systemic lupus erythematosus (SLE) and developed composite indices for interpreting ANAM results. Our objectives here were to provide further support for the ANAM's concurrent criterion validity against the American College of Rheumatology neuropsychological battery (ACR-NB), identify the most discriminatory subtests and scores of the ANAM for predicting CI, and provide a new approach to interpret ANAM results using Classification and Regression Tree (CART) analysis.Methods300 adult SLE patients completed an adapted ACR-NB and ANAM on the same day. As per objectives, six models were built using combinations of ANAM subtests and scores and submitted to CART analysis. Area under the curve (AUC) was calculated to evaluate the ANAM's criterion validity compared to the adapted ACR-NB; the most discriminatory ANAM subtests and scores in each model were selected, and performance of models with the highest AUCs were compared to our previous composite indices; decision trees were generated for models with the highest AUCs.ResultsTwo models had excellent AUCs of 86 and 89%. Eight most discriminatory ANAM subtests and scores were identified. Both models demonstrated higher AUCs against our previous composite indices. An adapted decision tree was created to simplify the interpretation of ANAM results.ConclusionWe provide further validity evidence for the ANAM as a valid CI screening tool in SLE. The decision tree improves interpretation of ANAM results, enhancing clinical utility.

Membranous nephropathy is an uncommon cause of nephrotic syndrome in pediatrics. We reviewed our kidney biopsy records for patients ≤ 20 years of age with membranous nephropathy without evidence of systemic lupus erythematosus within 6 months of biopsy (January 1995-September 2020). Staining for PLA2R, NELL1, THSD7A, SEMA3B, EXT2 (3 biopsies), and IgG-subclass were performed. Sixteen children (≤ 12 years) and 25 adolescents (13-20 years) were identified. Four children and 15 adolescents showed autoantigen positivity: PLA2R+/SEMA3B- (13), SEMA3B+/PLA2R+ (2), SEMA3B+/PLA2R- (1), NELL1 (1), EXT2+ (2), and THSD7A (0). Co-morbidities associated with PLA2R positivity included IPEX syndrome, active hepatitis B, Von Hippel Lindau syndrome, solitary kidney, type 1 diabetes, hyperuricemia, pregnancy (1), obesity (3), type II diabetes, H. pylori, viral prodrome, and nephrolithiasis. The SEMA3B+/PLA2R- adolescent was pregnant, the NELL1+ adolescent was obese, and the two EXT2+ adolescents eventually met the clinical criteria for lupus (4, 9 years post-biopsy). Co-morbidities among the remaining 24 patients included remote hepatitis B (2), Down's syndrome, lysinuric protein intolerance, recurrent UTIs, hypothyroidism, pregnancy (3), and obesity (2). Follow-up data was available for 12 children and 16 adolescents. Of the 12 children, 6 achieved complete remission, 4 achieved partial remission, and 2 had no response to treatment (1 transplant). Of the 16 adolescents, 4 achieved complete remission, 4 achieved partial remission, and 8 had no response to treatment (3 transplants). A child with "full-house" immunofluorescence staining achieved spontaneous disease remission. Our non-lupus membranous nephropathy cohort represents one of the largest pediatric studies to date. A higher resolution version of the Graphical abstract is available as Supplementary information.

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren's syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

ObjectivesPatients with systemic lupus erythematosus (SLE) have a high risk of cardiovascular disease that could potentially increase postoperative major adverse cardiac events (MACE). We determined the rate of MACE in patients with SLE undergoing noncardiac surgery using national claims-based data.MethodsThis was a retrospective cohort study using Optum Clinformatics Data Mart from 2007 to 2020. We identified a cohort of patients with SLE who had undergone noncardiac surgeries using Current Procedural Terminology codes. We also identified two control cohorts without SLE, one with diabetes mellitus (DM) and one without DM. After matching cases and controls by age and sex, the odds of MACE were estimated using multivariable logistic regression models also including race and the Revised Cardiac Risk Index (RCRI) scores. We also examined use of preoperative cardiac testing.ResultsWe identified 4750 patients with SLE, 496,381 DM controls, and 1,484,986 non-DM controls. After matching, the odds ratio (OR) for MACE in patients with SLE versus non-DM controls was 1.51 (95% confidence interval 1.09-2.08), which decreased after adjustment for RCRI score (OR: 0.97, 95% confidence interval 0.7-1.36). No significant differences were observed in the incidence of MACE between patients with SLE and DM controls (0.82 vs 1.04, P = 0.16). High-risk patients with SLE (RCRI score of ≥3) were less likely to receive preoperative cardiac testing than non-DM controls (42.7% vs 35.1%, P < 0.05).ConclusionPatients with SLE have an increased risk of postoperative MACE, which is driven by increased RCRI scores. Concerningly, high-risk patients received less cardiac testing 2 months before surgery than non-DM controls.

ObjectivesIn the anifrolumab systemic lupus erythematosus (SLE) trial programme, there was one trial (TULIP-1) in which BILAG-based Composite Lupus Assessment (BICLA) responses favoured anifrolumab over placebo, but the SLE Responder Index (SRI(4)) treatment difference was not significant. We investigated the degree of concordance between BICLA and SRI(4) across anifrolumab trials in order to better understand drivers of discrepant SLE trial results.MethodsTULIP-1, TULIP-2 (both phase 3) and MUSE (phase 2b) were randomised, 52-week trials of intravenous anifrolumab (300 mg every 4 weeks, 48 weeks; TULIP-1/TULIP-2: n=180; MUSE: n=99) or placebo (TULIP-1: n=184, TULIP-2: n=182; MUSE: n=102). Week 52 BICLA and SRI(4) outcomes were assessed for each patient.ResultsMost patients (78%-85%) had concordant BICLA and SRI(4) outcomes (Cohen's Kappa 0.6-0.7, nominal p<0.001). Dual BICLA/SRI(4) response rates favoured anifrolumab over placebo in TULIP-1, TULIP-2 and MUSE (all nominal p≤0.004). A discordant TULIP-1 BICLA non-responder/SRI(4) responder subgroup was identified (40/364, 11% of TULIP-1 population), comprising more patients receiving placebo (n=28) than anifrolumab (n=12). In this subgroup, placebo-treated patients had lower baseline disease activity, joint counts and glucocorticoid tapering rates, and more placebo-treated patients had arthritis response than anifrolumab-treated patients.ConclusionsAcross trials, most patients had concordant BICLA/SRI(4) outcomes and dual BICLA/SRI(4) responses favoured anifrolumab. A BICLA non-responder/SRI(4) responder subgroup was identified where imbalances of key factors driving the BICLA/SRI(4) discordance (disease activity, glucocorticoid taper) disproportionately favoured the TULIP-1 placebo group. Careful attention to baseline disease activity and monitoring glucocorticoid taper variation will be essential in future SLE trials.Trial registration numbersNCT02446912 and NCT02446899.

AimTo determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19.MethodsPeople with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity.ResultsA total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1-5 mg/day 1.86, 1.20 to 2.66, 6-9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab.ConclusionsMore severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.

ObjectivesTo characterise the efficacy and safety of anifrolumab in patients with systemic lupus erythematosus (SLE) according to interferon gene signature (IFNGS), demographic and clinical subgroups.MethodsWe performed post hoc analyses of pooled data from the 52-week phase III TULIP-1/TULIP-2 placebo-controlled trials of intravenous anifrolumab in moderate-to-severe SLE. Outcomes were assessed in predefined subgroups: IFNGS (high/low), age, sex, body mass index, race, geographic region, age of onset, glucocorticoid use, disease activity and serological markers.ResultsIn pooled data, patients received anifrolumab 300 mg (360/726) or placebo (366/726); 82.6% were IFNGS-high. IFNGS-high patients had greater baseline disease activity and were more likely to have abnormal serological markers versus IFNGS-low patients. In the total population, a greater proportion of patients treated with anifrolumab versus placebo achieved British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at week 52 (difference 16.6%; nominal p<0.001). BICLA response treatment differences with anifrolumab versus placebo were comparable to the total population across most predefined subgroups, including subgroups for baseline glucocorticoid dosage (<10/≥10 mg/day prednisone/equivalent) and for clinical disease activity (SLE Disease Activity Index 2000 score <10/≥10). Subgroups with larger treatment differences included IFNGS-high patients (18.2%), patients with abnormal baseline serological markers (23.1%) and Asian patients (29.2%). The safety profile of anifrolumab was similar across subgroups.ConclusionsOverall, this study supports the consistent efficacy and safety of anifrolumab across a range of patients with moderate-to-severe SLE. In a few subgroups, small sample sizes limited conclusions from being drawn regarding the treatment benefit with anifrolumab.Trial registration numberNCT02446912, NCT02446899.

Here, we report that the LynB splice variant of the Src-family kinase Lyn exerts a dominant immunosuppressive function in vivo, whereas the LynA isoform is uniquely required to restrain autoimmunity in female mice. We used CRISPR-Cas9 gene editing to constrain lyn splicing and expression, generating single-isoform LynA knockout (LynAKO) or LynBKO mice. Autoimmune disease in total LynKO mice is characterized by production of antinuclear antibodies, glomerulonephritis, impaired B cell development, and overabundance of activated B cells and proinflammatory myeloid cells. Expression of LynA or LynB alone uncoupled the developmental phenotype from the autoimmune disease: B cell transitional populations were restored, but myeloid cells and differentiated B cells were dysregulated. These changes were isoform-specific, sexually dimorphic, and distinct from the complete LynKO. Despite the apparent differences in disease etiology and penetrance, loss of either LynA or LynB had the potential to induce severe autoimmune disease with parallels to human systemic lupus erythematosus (SLE).

Genome-wide association studies have identified 2p13.1 as a prominent susceptibility locus for systemic lupus erythematosus (SLE)-a complex, multisystem autoimmune disease. However, the identity of underlying causal variant (s) and molecular mechanisms for increasing disease susceptibility are poorly understood. Using meta-analysis (cases = 10,252, controls = 21,604) followed by conditional analysis, bioinformatic annotation, and eQTL and 3D-chromatin interaction analyses, we computationally prioritized potential functional variants and subsequently experimentally validated their effects. Ethnicity-specific meta-analysis revealed striking allele frequency differences between Asian and European ancestries, but with similar odds ratios. We identified 20 genome-wide significant (p < 5 × 10-8) variants, and conditional analysis pinpointed two potential functional variants, rs6705628 and rs2272165, likely to explain the association. The two SNPs are near DGUOK, mitochondrial deoxyguanosine kinase, and its associated antisense RNA DGUOK-AS1. Using luciferase reporter gene assays, we found significant cell type- and allele-specific promoter activity at rs6705628 and enhancer activity at rs2272165. This is supported by ChIP-qPCR showing allele-specific binding with three histone marks (H3K27ac, H3K4me3, and H3K4me1), RNA polymerase II (Pol II), transcriptional coactivator p300, CCCTC-binding factor (CTCF), and transcription factor ARID3A. Transcriptome data across 28 immune cell types from Asians showed both SNPs are cell-type-specific but only in B-cells. Splicing QTLs showed strong regulation of DGUOK-AS1. Genotype-specific DGOUK protein levels are supported by Western blots. Promoter capture Hi-C data revealed long-range chromatin interactions between rs2272165 and several nearby promoters, including DGUOK. Taken together, we provide mechanistic insights into how two noncoding variants underlie SLE risk at the 2p13.1 locus.

BackgroundMembranous nephropathy is an uncommon cause of nephrotic syndrome in pediatrics.MethodsWe reviewed our kidney biopsy records for patients ≤ 20 years of age with membranous nephropathy without evidence of systemic lupus erythematosus within 6 months of biopsy (January 1995-September 2020). Staining for PLA2R, NELL1, THSD7A, SEMA3B, EXT2 (3 biopsies), and IgG-subclass were performed.ResultsSixteen children (≤ 12 years) and 25 adolescents (13-20 years) were identified. Four children and 15 adolescents showed autoantigen positivity: PLA2R+/SEMA3B- (13), SEMA3B+/PLA2R+ (2), SEMA3B+/PLA2R- (1), NELL1 (1), EXT2+ (2), and THSD7A (0). Co-morbidities associated with PLA2R positivity included IPEX syndrome, active hepatitis B, Von Hippel Lindau syndrome, solitary kidney, type 1 diabetes, hyperuricemia, pregnancy (1), obesity (3), type II diabetes, H. pylori, viral prodrome, and nephrolithiasis. The SEMA3B+/PLA2R- adolescent was pregnant, the NELL1+ adolescent was obese, and the two EXT2+ adolescents eventually met the clinical criteria for lupus (4, 9 years post-biopsy). Co-morbidities among the remaining 24 patients included remote hepatitis B (2), Down's syndrome, lysinuric protein intolerance, recurrent UTIs, hypothyroidism, pregnancy (3), and obesity (2). Follow-up data was available for 12 children and 16 adolescents. Of the 12 children, 6 achieved complete remission, 4 achieved partial remission, and 2 had no response to treatment (1 transplant). Of the 16 adolescents, 4 achieved complete remission, 4 achieved partial remission, and 8 had no response to treatment (3 transplants). A child with "full-house" immunofluorescence staining achieved spontaneous disease remission.ConclusionOur non-lupus membranous nephropathy cohort represents one of the largest pediatric studies to date. A higher resolution version of the Graphical abstract is available as Supplementary information.

ObjectiveGlucocorticoids are part of standard therapy for systemic lupus erythematosus (SLE), despite adverse effects associated with long-term treatment. Belimumab improved clinical manifestations of SLE and reduced glucocorticoid doses in clinical trials and clinical practice; however, associations have not been examined using multi-institutional electronic health record (EHR) data. Using the Rheumatology Informatics System for Effectiveness registry, we examined glucocorticoid use patterns among belimumab-treated adults with SLE.MethodsThis retrospective analysis (GSK Study 209267) used EHR prescription records of patients with SLE managed by rheumatologists. Eligible patients had an index date (first belimumab prescription) between January 2014 and June 2018. The primary analysis compared patients' mean daily oral glucocorticoid (prednisone equivalent) dose over the 6 months preindex versus 6 months post index. An exploratory analysis assessed glucocorticoid doses at 12 and 24 months post index for patients with extended follow-up.ResultsOf the 1987 patients receiving their first belimumab prescription, 767 had available glucocorticoid prescribing data, whereas 204 (primary analysis population) had glucocorticoids prescribed in the 6 months preindex and received belimumab according to the prescribing information for the first 8 weeks post index. The mean (SD) glucocorticoid dose was 12.5 (13.5) mg/day 3 months preindex, reducing to 10.3 (10.6) mg/day over the 6 months post index, and 8.7 (9.4) and 9.0 (9.3) mg/day at 12 and 24 months post index.ConclusionThis study showed reductions in mean daily glucocorticoid dose after belimumab initiation. Several limitations of EHRs for real-world effectiveness research were identified, which limited interpretation of results and may inform future study designs.

AimTo determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19.MethodsPeople with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity.ResultsA total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1-5 mg/day 1.86, 1.20 to 2.66, 6-9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab.ConclusionsMore severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.

ObjectiveWe previously demonstrated the utility of the Automated Neuropsychological Assessment Metrics (ANAM) for screening cognitive impairment (CI) in patients with systemic lupus erythematosus (SLE) and developed composite indices for interpreting ANAM results. Our objectives here were to provide further support for the ANAM's concurrent criterion validity against the American College of Rheumatology neuropsychological battery (ACR-NB), identify the most discriminatory subtests and scores of the ANAM for predicting CI, and provide a new approach to interpret ANAM results using Classification and Regression Tree (CART) analysis.Methods300 adult SLE patients completed an adapted ACR-NB and ANAM on the same day. As per objectives, six models were built using combinations of ANAM subtests and scores and submitted to CART analysis. Area under the curve (AUC) was calculated to evaluate the ANAM's criterion validity compared to the adapted ACR-NB; the most discriminatory ANAM subtests and scores in each model were selected, and performance of models with the highest AUCs were compared to our previous composite indices; decision trees were generated for models with the highest AUCs.ResultsTwo models had excellent AUCs of 86 and 89%. Eight most discriminatory ANAM subtests and scores were identified. Both models demonstrated higher AUCs against our previous composite indices. An adapted decision tree was created to simplify the interpretation of ANAM results.ConclusionWe provide further validity evidence for the ANAM as a valid CI screening tool in SLE. The decision tree improves interpretation of ANAM results, enhancing clinical utility.

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren's syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

ObjectivesPatients with systemic lupus erythematosus (SLE) have a high risk of cardiovascular disease that could potentially increase postoperative major adverse cardiac events (MACE). We determined the rate of MACE in patients with SLE undergoing noncardiac surgery using national claims-based data.MethodsThis was a retrospective cohort study using Optum Clinformatics Data Mart from 2007 to 2020. We identified a cohort of patients with SLE who had undergone noncardiac surgeries using Current Procedural Terminology codes. We also identified two control cohorts without SLE, one with diabetes mellitus (DM) and one without DM. After matching cases and controls by age and sex, the odds of MACE were estimated using multivariable logistic regression models also including race and the Revised Cardiac Risk Index (RCRI) scores. We also examined use of preoperative cardiac testing.ResultsWe identified 4750 patients with SLE, 496,381 DM controls, and 1,484,986 non-DM controls. After matching, the odds ratio (OR) for MACE in patients with SLE versus non-DM controls was 1.51 (95% confidence interval 1.09-2.08), which decreased after adjustment for RCRI score (OR: 0.97, 95% confidence interval 0.7-1.36). No significant differences were observed in the incidence of MACE between patients with SLE and DM controls (0.82 vs 1.04, P = 0.16). High-risk patients with SLE (RCRI score of ≥3) were less likely to receive preoperative cardiac testing than non-DM controls (42.7% vs 35.1%, P < 0.05).ConclusionPatients with SLE have an increased risk of postoperative MACE, which is driven by increased RCRI scores. Concerningly, high-risk patients received less cardiac testing 2 months before surgery than non-DM controls.

ObjectivesTo characterise the efficacy and safety of anifrolumab in patients with systemic lupus erythematosus (SLE) according to interferon gene signature (IFNGS), demographic and clinical subgroups.MethodsWe performed post hoc analyses of pooled data from the 52-week phase III TULIP-1/TULIP-2 placebo-controlled trials of intravenous anifrolumab in moderate-to-severe SLE. Outcomes were assessed in predefined subgroups: IFNGS (high/low), age, sex, body mass index, race, geographic region, age of onset, glucocorticoid use, disease activity and serological markers.ResultsIn pooled data, patients received anifrolumab 300 mg (360/726) or placebo (366/726); 82.6% were IFNGS-high. IFNGS-high patients had greater baseline disease activity and were more likely to have abnormal serological markers versus IFNGS-low patients. In the total population, a greater proportion of patients treated with anifrolumab versus placebo achieved British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at week 52 (difference 16.6%; nominal p<0.001). BICLA response treatment differences with anifrolumab versus placebo were comparable to the total population across most predefined subgroups, including subgroups for baseline glucocorticoid dosage (<10/≥10 mg/day prednisone/equivalent) and for clinical disease activity (SLE Disease Activity Index 2000 score <10/≥10). Subgroups with larger treatment differences included IFNGS-high patients (18.2%), patients with abnormal baseline serological markers (23.1%) and Asian patients (29.2%). The safety profile of anifrolumab was similar across subgroups.ConclusionsOverall, this study supports the consistent efficacy and safety of anifrolumab across a range of patients with moderate-to-severe SLE. In a few subgroups, small sample sizes limited conclusions from being drawn regarding the treatment benefit with anifrolumab.Trial registration numberNCT02446912, NCT02446899.

ObjectivesIn the anifrolumab systemic lupus erythematosus (SLE) trial programme, there was one trial (TULIP-1) in which BILAG-based Composite Lupus Assessment (BICLA) responses favoured anifrolumab over placebo, but the SLE Responder Index (SRI(4)) treatment difference was not significant. We investigated the degree of concordance between BICLA and SRI(4) across anifrolumab trials in order to better understand drivers of discrepant SLE trial results.MethodsTULIP-1, TULIP-2 (both phase 3) and MUSE (phase 2b) were randomised, 52-week trials of intravenous anifrolumab (300 mg every 4 weeks, 48 weeks; TULIP-1/TULIP-2: n=180; MUSE: n=99) or placebo (TULIP-1: n=184, TULIP-2: n=182; MUSE: n=102). Week 52 BICLA and SRI(4) outcomes were assessed for each patient.ResultsMost patients (78%-85%) had concordant BICLA and SRI(4) outcomes (Cohen's Kappa 0.6-0.7, nominal p<0.001). Dual BICLA/SRI(4) response rates favoured anifrolumab over placebo in TULIP-1, TULIP-2 and MUSE (all nominal p≤0.004). A discordant TULIP-1 BICLA non-responder/SRI(4) responder subgroup was identified (40/364, 11% of TULIP-1 population), comprising more patients receiving placebo (n=28) than anifrolumab (n=12). In this subgroup, placebo-treated patients had lower baseline disease activity, joint counts and glucocorticoid tapering rates, and more placebo-treated patients had arthritis response than anifrolumab-treated patients.ConclusionsAcross trials, most patients had concordant BICLA/SRI(4) outcomes and dual BICLA/SRI(4) responses favoured anifrolumab. A BICLA non-responder/SRI(4) responder subgroup was identified where imbalances of key factors driving the BICLA/SRI(4) discordance (disease activity, glucocorticoid taper) disproportionately favoured the TULIP-1 placebo group. Careful attention to baseline disease activity and monitoring glucocorticoid taper variation will be essential in future SLE trials.Trial registration numbersNCT02446912 and NCT02446899.

Here, we report that the LynB splice variant of the Src-family kinase Lyn exerts a dominant immunosuppressive function in vivo, whereas the LynA isoform is uniquely required to restrain autoimmunity in female mice. We used CRISPR-Cas9 gene editing to constrain lyn splicing and expression, generating single-isoform LynA knockout (LynAKO) or LynBKO mice. Autoimmune disease in total LynKO mice is characterized by production of antinuclear antibodies, glomerulonephritis, impaired B cell development, and overabundance of activated B cells and proinflammatory myeloid cells. Expression of LynA or LynB alone uncoupled the developmental phenotype from the autoimmune disease: B cell transitional populations were restored, but myeloid cells and differentiated B cells were dysregulated. These changes were isoform-specific, sexually dimorphic, and distinct from the complete LynKO. Despite the apparent differences in disease etiology and penetrance, loss of either LynA or LynB had the potential to induce severe autoimmune disease with parallels to human systemic lupus erythematosus (SLE).

Wolf isotopic response represents the development of skin lesions of one particular morphology occurring at the same site as another morphologically distinct and unrelated skin lesion. Cutaneous lupus erythematosus (CLE) is an autoimmune connective tissue disorder encompassing a wide range of phenotypes that may be associated with systemic involvement. Although CLE is a well-described entity with a broad spectrum, the occurrence of lesions manifesting as an isotopic response is rare. We present a patient with systemic lupus erythematosus who developed CLE in a dermatomal distribution following herpes zoster. When CLE lesions present in a dermatomal distribution, these cases may be difficult to distinguish from recurrent herpes zoster infection in an immunosuppressed patient. Therefore, they pose a diagnostic challenge and require balancing antiviral therapy with immunosuppression to sufficiently maintain adequate control of the autoimmune disease while addressing possible infections. To avoid treatment delay, clinicians should have elevated suspicion for an isotopic response when disparate lesions erupt in areas previously affected by herpes zoster or in cases of persistent eruptions at sites of prior herpes zoster. We discuss this case within the context of Wolf isotopic response and review the literature for similar cases.

Background : Cases of uterine wall thinning and placental abnormalities complicated with systemic lupus erythematosus (SLE) during pregnancy have been reported in Asian countries for ten years. Long-term steroid use can cause muscle degeneration, but the mechanism of myometrium thinning was not known. Through the review of published articles, this report is the first review of cases to discuss the pathogenesis and clinical features of thinned myometrium and placenta accreta spectrum (PAS) in pregnant patients with SLE. Case presentation : A twenty-nine-year-old primigravida with a history of lupus enteritis and paralytic ileus had a natural conception after less than two years of steroid treatment. An ultrasonographic study showed a thin uterine wall with a widespread thick placenta on the entire surface of the uterine cavity in the third trimester. At the 39th gestational week, she underwent a cesarean section due to the failure of the uterus to contract, even though the injection of oxytocin. There were several engorged vessels on the surface of the anterior uterine wall at the time of laparotomy. We decided to perform a hysterectomy because diffuse PAS replaced her uterus. Conclusion : A review of reported cases and our case shows an unusual complication of SLE that might be related to the particular condition of the estrogen-mediated immune system. Clinicians should always pay attention to the possibility of uterine wall thinning as uterine atony and the structural abnormality of the placenta for SLE patients with the unscarred uterus.

ObjectiveAlthough multiple national quality measures focus on the management and safety of rheumatoid arthritis, few measures address the care of patients with systemic lupus erythematosus (SLE). Our objective was to apply a group of quality measures relevant to the care of patients with SLE, and we used the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry to assess nationwide variations in care.MethodsThe data derived from RISE and included patients who had ≥2 visits with SLE codes ≥30 days apart in 2017-2018. We calculated performance on 5 quality measures: renal disease screening, blood pressure assessment and management, hydroxychloroquine (HCQ) prescribing, safe dosing for HCQ, and prolonged glucocorticoid use at doses of >7.5 mg/day. We reported performance on these measures at the practice level. We used logistic regression to assess independent predictors of performance after adjusting for sociodemographic and utilization factors.ResultsWe included 27,567 unique patients from 186 practices; 91.7% were female and 48% White, with a mean age of 53.5 ± 15.2 years. Few patients had adequate screening for the development of renal manifestations (39.5%). Although blood pressure assessment was common (94.4%), a meaningful fraction of patients had untreated hypertension (17.7%). Many received HCQ (71.5%), but only 62% at doses of ≤5.0 mg/kg/day. Some received at least moderate-dose steroids for ≥90 days (18.5%). We observed significant practice variation on every measure.ConclusionWe found potential gaps in care for patients with SLE across the US. Although some performance variation may be explained by differences in disease severity, dramatic differences suggest that developing quality measures to address important health care processes in SLE may improve care.