A human-mouse atlas of intrarenal myeloid cells identifies conserved disease-associated macrophages in lupus nephritis.

Monocytes and macrophages in patients with lupus nephritis exhibit altered behavior compared with healthy kidneys. How to optimally use mouse models to develop treatments targeting these cells is poorly understood. This study compared intrarenal myeloid cells in four mouse models and 155 lupus nephritis patients using single-cell profiling, spatial transcriptomics, and functional studies.

Genetic and epigenetic dysregulation of CR1 is associated with catastrophic antiphospholipid syndrome.

Objectives: Catastrophic antiphospholipid syndrome (CAPS) is a complement-driven thrombotic disorder, characterised by widespread thrombosis and multiorgan failure. We identified rare germline variants including complement receptor 1 (CR1) in 50% of patients with CAPS. Here, we define CR1 dysregulation mechanisms (genetic/epigenetic) underlying complement-mediated thrombosis in CAPS and support C5 inhibition as a potential therapy.

Fragmentation signatures in cancer patients resemble those of patients with vascular or autoimmune diseases.

Multiple case-controlled studies have shown that analyzing fragmentation patterns in plasma cell-free DNA (cfDNA) can distinguish individuals with cancer from healthy controls. However, there have been few studies that investigate various types of cfDNA fragmentomics patterns in individuals with other diseases. We therefore developed a comprehensive statistic, called fragmentation signatures, that integrates the distributions of fragment positioning, fragment length, and fragment end-motifs in cfDNA.

Antiphospholipid antibody-related clinical manifestations during childhood versus adulthood: descriptive results from the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) clinical database and repository.

Objectives: There is a limited number of studies comparing paediatric to adult antiphospholipid syndrome (APS) patients. Our objective was to analyse the characteristics of patients presenting with antiphospholipid antibody (aPL)-related clinical manifestations during childhood versus adulthood.

Methods: We retrieved baseline characteristics from an international registry of persistently aPL-positive adult patients.

Development of the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria, Phase III-C Report: Assessment of Patient Scenarios (Derivation Cohort) and Refinement of Definitions.

Objective: The 2023 ACR/EULAR Antiphospholipid Syndrome (APS) Classification criteria aim to identify patients with high likelihood of APS for research. Phases I/II of our four-phase methodological approach resulted in 27 candidate criteria organized in clinical and laboratory domains. Here, we summarize Phase III efforts to reduce and refine criteria using patient scenarios.

Blood immunophenotyping identifies distinct kidney histopathology and outcomes in patients with lupus nephritis.

Lupus nephritis (LN) is a frequent manifestation of systemic lupus erythematosus, and fewer than half of patients achieve complete renal response with standard immunosuppressants. Identifying noninvasive, blood-based immune alterations associated with renal injury could aid therapeutic decisions. Here, we used mass cytometry immunophenotyping of peripheral blood mononuclear cells in 145 patients with biopsy-proven LN and 40 healthy controls to evaluate the heterogeneity of immune activation and identify correlates of renal parameters.

ERN ReCONNET-SLICC-SLEuro expert consensus on the therapeutic management of rare systemic lupus erythematosus manifestations.

Existing guidelines for systemic lupus erythematosus (SLE) predominantly focus on common and major organ involvements. An international taskforce involving experts from three SLE expert groups (ie, the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, the Systemic Lupus Erythematosus International Collaborating Clinics group, and the European Lupus Society) was established. A total of 119 participants contributed to the development of consensus therapeutic strategies for 24 rare SLE manifestations, using a multistep process.

Genetic and Epigenetic Dysregulation of CR1 is Associated with Catastrophic Antiphospholipid Syndrome (CAPS).

Objective: Catastrophic antiphospholipid syndrome (CAPS), characterized by widespread thrombosis and multi-organ failure, is associated with high morbidity and mortality. We previously established complement activation as a pathogenic driver of CAPS and identified rare germline variants in complement-regulatory genes including Complement Receptor 1 () in 50% of CAPS.

Methods: We quantified CR1 expression by flow cytometry across hematopoietic cell types.

Anti-TFAM antibodies link mitochondrial damage with antiphospholipid syndrome and thrombosis in SLE.

Objectives: Mitochondria are a source of autoantigens and damage-associated molecular patterns (DAMPs) in systemic lupus erythematosus (SLE). Nucleoids carrying TFAM (transcription factor A, mitochondrial) and mitochondrial DNA (mtDNA) are important DAMPs in SLE. While mtDNA has been associated with anti-double-stranded (ds)DNA antibodies and type I interferon (IFN-I), the immunogenic role of TFAM in SLE pathogenesis is unknown.

Direct oral anticoagulants versus Vitamin K antagonists in antiphospholipid syndrome: A systematic review and meta-analysis.

Background: Randomized controlled trials (RCTs) comparing the efficacy and safety of direct oral anticoagulants (DOACs) versus Vitamin K antagonists (VKAs) in patients with thrombotic antiphospholipid syndrome (APS) have yielded inconsistent results, partly due to the inherent challenges of conducting RCTs in populations with rare medical conditions. We conducted a systematic review and meta-analysis to evaluate the comparative effects of DOACs versus VKAs in thrombotic APS.

Methods: RCTs and observational studies comparing DOACs versus VKAs in patients with thrombotic APS were included.

Thrombocytopenia and autoimmune hemolytic anemia in antiphospholipid antibody-positive patients: Descriptive analysis of the AntiPhospholipid syndrome alliance for clinical trials and InternatiOnal networking (APS ACTION) clinical database and repository ("Registry").

Background/PurposeAPS ACTION Registry was created to study the natural course of antiphospholipid syndrome (APS) over 10 years in persistently antiphospholipid antibody (aPL) positive patients with or without systemic autoimmune rheumatic diseases (SARDs). Our primary objective was to compare the characteristics of aPL-positive patients with or without thrombocytopenia (TP) and/or autoimmune hemolytic anemia (AIHA).MethodsThe registry inclusion criteria are positive aPL based on the Revised Sapporo APS Classification Criteria, tested at least twice within 1 year prior to enrollment.

Incidence and Factors Associated With Recurrent Pericarditis in Lupus.

Importance: Pericarditis is the most common cardiac manifestation of systemic lupus erythematosus (SLE) and is known to recur among patients. However, the prevalence of and risk factors associated with recurrent pericarditis in patients with SLE were unknown.

Objective: To investigate the frequency of and risk factors associated with the recurrence of pericarditis in patients with SLE.

Second Trimester Kidney Function and Adverse Pregnancy Outcomes among Patients with Lupus.

Key Points: In our combined cohort, second trimester kidney function was associated with adverse outcomes for patients with lupus. Measurement of kidney function during pregnancy may have potential benefit, especially among patients without kidney disease.

Background: Kidney function is not routinely assessed during pregnancy.

Predictors of Mortality in Antiphospholipid Antibody-Positive Patients: Prospective Results From Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository.

Objective: The objective was to determine the mortality rate as well as the causes and predictors of death in antiphospholipid antibody (aPL)-positive patients with and without antiphospholipid syndrome (APS) classification.

Methods: The inclusion criterion for the multicenter international Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) registry is positive aPLs according to the Revised Sapporo Classification Criteria tested within one year before enrollment. Patients are observed every 12 ± 3 months with clinical data and blood collection.

Patients achieving low lupus disease activity state, systemic lupus erythematosus disease control or remission showed lower rates of organ damage during longitudinal follow-up: analysis of the Hopkins Lupus Cohort.

Objective: One key target of treating patients with systemic lupus erythematosus (SLE) is to prevent organ damage. This analysis quantified the association between time spent in four specific SLE low disease activity (LDA) states and organ damage rate.

Methods: This retrospective real-world data analysis (GSK Study 207168), undertaken to help contextualise the BLISS-BELIEVE clinical trial, included adults with SLE enrolled for≥1 year in the Hopkins Lupus Cohort and treated with standard therapy in a specialist care centre between 1987 and 2019.

Inflammation in Areas of Fibrosis Precedes Loss of Kidney Function in Lupus Nephritis.

Background: Interstitial fibrosis in lupus nephritis (LN) is often infiltrated by immune cells but typically regarded as nonspecific "scar reaction." This study aimed to investigate the relationship between inflammatory fibrosis and kidney disease progression in LN.

Methods: Interstitial fibrosis and tubular atrophy (IFTA) were scored in 124 LN kidney biopsies.

Soluble urine activated leukocyte cell adhesion molecule is a strong predictor of lupus nephritis.

Objectives: To evaluate urinary activated leucocyte cell adhesion molecule (ALCAM) and CD6 as predictors of LN progression or disease resolution across a 1-year study.

Methods: Serum and urine samples from biopsy proven LN subjects (n = 122) were prospectively collected over the course of a year at 3- or 6-month intervals (weeks 0, 12, 26 and 52) across multiple study sites and assessed for soluble ALCAM and CD6 levels. Urine creatinine from the same urine sample was used to normalize the levels of urinary ALCAM and urinary CD6.

Association Between 25-hydroxyvitamin D Levels and Adverse Pregnancy Outcomes in Systemic Lupus Erythematosus.

Objective: We evaluated the association of 25-hydroxyvitamin D (25(OH)D) levels with adverse pregnancy outcomes in systemic lupus erythematosus (SLE).

Methods: The Hopkins Lupus Cohort includes visits of pregnant patients, including assessment of 25(OH)D levels at each visit. We examined the relationship between 25(OH)D levels and adverse pregnancy outcomes (miscarriage, preterm delivery, and small for gestational age).

SOX-5 Transcription Factor: a Novel Psoriatic Autoantigen Preferentially Found in Women.

Objective: Adaptive immunity mediates psoriatic disease pathogenesis. We aimed to identify novel psoriatic autoantigens and their phenotypic associations in deeply characterized patient cohorts.

Methods: Sera from psoriatic arthritis (PsA) patients were used for autoantibody discovery.

Association of Autoantibody Concentrations and Trajectories With Lupus Nephritis Histologic Features and Treatment Response.

Objective: Autoantibodies are a hallmark of lupus nephritis (LN), but their association with LN classes and treatment response are not adequately known. In this study, we quantified circulating autoantibodies in the Accelerating Medicines Partnership LN longitudinal cohort to identify serological biomarkers of LN histologic classification and treatment response and how these biomarkers change over time based on treatment response.

Methods: Peripheral blood samples were collected from 279 patients with systemic lupus erythematosus undergoing diagnostic kidney biopsy based on proteinuria.