What's new in the assessment of lupus activity?

Capturing disease activity in SLE remains challenging. The binary nature of global score indices such as the SLEDAI 2000 (SLEDAI-2K) poses limitations, while the complexity of the BILAG-2004 index requires training and more time investment. Recent efforts to improve SLE activity indices include the SLE Disease Activity Score (SLE-DAS) and Easy-BILAG system.

Effect of rituximab on long-term damage acquisition in patients with systemic lupus erythematosus.

Objectives: B-cell depletion therapy has been used for over two decades to treat SLE, but there is a lack of studies reporting its impact on damage progression. This study aims to assess the effectiveness of rituximab in slowing damage acquisition.

Methods: We selected 380 patients 190 treated with rituximab and 190 controls, based on matched sex and age of onset, with standard immunosuppressive therapies-to compare the damage they developed, assessed by the SLICC/ACR Damage Index (DI).

Baby you can drive my CAR-T cells.

ObjectiveTo evaluate the potential of chimeric antigen receptor T-cell (CAR-T) therapy in revolutionizing the treatment of systemic lupus erythematosus (SLE) and to outline necessary future steps for its implementation.MethodsA careful literature search was conducted for relevant English language papers on pubmed.ResultsPreliminary data suggest that CAR-T therapy could significantly improve SLE outcomes.

Risk factors for bleeding in patients with thrombotic antiphospholipid syndrome during antithrombotic therapy.

ObjectivesWe aimed to explore the prevalence and risk factors for bleeding in patients with thrombotic antiphospholipid syndrome (tAPS) on antithrombotic therapy.MethodsSingle-centre retrospective analysis of patients with tAPS (Sydney criteria). Bleeding events were classified according to the International Society on Thrombosis and Haemostasis as (a) major bleeding and (b) any bleeding.

Development of CARRA/PReS-endorsed consensus Core and Expanded Datasets in childhood-onset systemic lupus erythematosus for international registry-based research.

Objectives: Childhood-onset systemic lupus erythematosus (cSLE), representing 15%-20% of individuals with SLE, has been difficult to study globally due to differences between registries. This initiative, supported by Childhood Arthritis Rheumatology Research Alliance (CARRA) and Paediatric Rheumatology European Society (PReS), aims to create Core and Expanded cSLE Datasets to standardise and enhance research worldwide.

Methods: 21 international cSLE experts and 4 patients participated in a Delphi process (questionnaires, 2 topic-specific focus groups and 3 virtual consensus meetings) to create 2 standardised cSLE datasets.

Damage Index for Antiphospholipid Syndrome (DIAPS): An Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) "Damage" working group report on strengths and limitations.

Objectives: To gather the perspectives of APS ACTION members regarding the strengths and limitations of Damage Index for Antiphospholipid Syndrome (DIAPS); and establish recommendations for the improvement of DIAPS.

Methods: APS ACTION members were invited to answer a survey regarding their satisfaction with DIAPS scoring system and individual items. The level of agreement (LoA) among members with the inclusion of individual items in DIAPS was calculated (LoA of <75% was considered disagreement).

Reduced response to SARS-CoV-2 vaccination is associated with impaired immunoglobulin class switch recombination in SLE patients.

Introduction: Systemic lupus erythematosus (SLE) patients exhibit B-cell abnormalities. Although there are concerns about reduced antibody responses to SARS-CoV-2 vaccines, detailed data on B-cell-specific responses in SLE remain scarce. Understanding the responsiveness to novel vaccine antigens, and boosters number, is important to avoid unnecessarily prolonged isolation of immunocompromised individuals.

An update on autoantibodies in the idiopathic inflammatory myopathies.

Myositis-specific autoantibodies (MSAs) have become pivotal biomarkers for idiopathic inflammatory myopathies and have revolutionized understanding of the heterogeneous disease spectrum that affects both adults and children. The discovery and characterization of MSAs have substantially enhanced patient stratification based on clinical phenotype, thereby facilitating more precise diagnosis and ultimately improving management strategies. Advances in immunoassay technologies in the past 20 years have further propelled the field forward, enabling the detection of a growing repertoire of autoantibodies with high specificity and sensitivity; however, evolving research over the past decade has revealed that even within antibody-defined subsets, considerable clinical diversity exists, suggesting a broader spectrum of disease manifestations than previously acknowledged.

Remission and low disease activity are associated with lower healthcare costs: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.

Objectives: This study aims to determine the independent impact of definitions of remission/low disease activity (LDA) on direct/indirect costs (DCs, ICs) in a multicentre inception cohort.

Methods: Patients from 31 centres in 10 countries were enrolled within 15 months of diagnosis and assessed annually. Five mutually exclusive disease activity states (DAS) were defined as (1) remission off-treatment: clinical (c) SLEDAI-2K=0, without prednisone/immunosuppressants; (2) remission on-treatment: cSLEDAI-2K=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; (3) LDA-Toronto Cohort (TC): cSLEDAI-2K≤2, without prednisone/immunosuppressants; (4) modified lupus LDA state (mLLDAS): SLEDAI-2K≤4, no activity in major organs/systems, no new activity, prednisone ≤7.

Thioredoxin is a metabolic rheostat controlling regulatory B cells.

Metabolic programming is important for B cell fate, but the bioenergetic requirement for regulatory B (B) cell differentiation and function is unknown. Here we show that B cell differentiation, unlike non-B cells, relies on mitochondrial electron transport and homeostatic levels of reactive oxygen species (ROS). Single-cell RNA sequencing analysis revealed that TXN, encoding the metabolic redox protein thioredoxin (Trx), is highly expressed by B cells, unlike Trx inhibitor TXNIP which was downregulated.

A large cohort comparison of very late-onset systemic lupus erythematosus with younger-onset patients.

Objectives: Age has a significant impact on systemic lupus erythematosus (SLE). However, data on very late-onset SLE (vlSLE) are scarce. We have compared the clinical and serological features of vlSLE patients with younger-onset patients.

Can complement activation be the missing link in antiphospholipid syndrome?

APS is an autoimmune disorder with life-threatening complications that, despite therapeutic advantages, remains associated with thrombotic recurrences and treatment failure. The role of complement activation in APS pathogenesis is increasingly recognized, specifically in obstetric APS. However, its exact role in thrombotic APS and on the severity of the disease is not yet fully elucidated.

Collaborative research in myositis-related disorders: MIHRA, a global shared community model.

Myositis International Health and Research Collaborative Alliance (MIHRA) is a newly formed purpose-built non-profit charitable research organization dedicated to accelerating international clinical trial readiness, global professional and lay education, career development and rare disease advocacy in IIM-related disorders. In its long form, the name expresses the community's scope of engagement and intent. In its abbreviation, MIHRA, conveys linguistic roots across many languages, that reflects the IIM community's spirit with meanings such as kindness, community, goodness, and peace.

Bleeding events in thrombotic antiphospholipid syndrome: prevalence, severity, and associated damage accrual.

Background: Life-long anticoagulation increases bleeding risk in patients with antiphospholipid syndrome (APS). The Damage Index for Antiphospholipid Syndrome does not include bleeding events in damage accrual.

Objectives: We aimed to characterize the prevalence, severity, and damage associated with bleeding events in patients with APS.

Where are we now in biologic drugs for myositis?

Idiopathic inflammatory myopathies (IIMs) are a rare and heterogeneous group of chronic autoimmune disorders. Up to 40% of IIM patients have long-term sequelae and significant functional disability. Its management can be challenging and new therapies are badly needed.

The impact of antiphospholipid antibodies/antiphospholipid syndrome on systemic lupus erythematosus.

aPLs are a major determinant of the increased cardiovascular risk in patients with SLE. They adversely affect clinical manifestations, damage accrual and prognosis. Apart from the antibodies included in the 2006 revised classification criteria for APS, other non-classical aPLs might help in identifying SLE patients at increased risk of thrombotic events.

Association Between Severe Nonadherence to Hydroxychloroquine and Systemic Lupus Erythematosus Flares, Damage, and Mortality in 660 Patients From the SLICC Inception Cohort.

Objective: The goals of this study were to assess the associations of severe nonadherence to hydroxychloroquine (HCQ), objectively assessed by HCQ serum levels, and risks of systemic lupus erythematosus (SLE) flares, damage, and mortality rates over five years of follow-up.

Methods: The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort is an international multicenter initiative (33 centers throughout 11 countries). The serum of patients prescribed HCQ for at least three months at enrollment were analyzed.

Promising Experimental Treatments for Lupus Nephritis: Key Talking Points and Potential Opportunities.

Lupus nephritis (LN) is a frequent and serious complication of systemic lupus erythematosus (SLE), impairing patients' quality of life and significantly increasing mortality. Despite optimizing the use of conventional immunosuppressants and other biological drugs, its management remains unsatisfactory. This is mainly due to the heterogeneity of SLE, but also to insufficiently effective treatment regimens and clinical trial limitations (strict criteria, low number of patients included, and side effects).

Survey on antiphospholipid syndrome diagnosis and antithrombotic treatment in patients with ischemic stroke, other brain ischemic injury, or arterial thromboembolism in other sites: communication from ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies.

Background: The optimal strategy for diagnosis and antithrombotic treatment of patients with antiphospholipid syndrome (APS)-associated acute ischemic stroke (AIS), transient ischemic attack (TIA), or other brain ischemic injury is poorly defined.

Objectives: The survey goal was to capture variations in diagnosis and antithrombotic treatment of APS-associated ischemic stroke and related disorders to inform guidance and clinical trials to define optimal management.

Methods: Professional colleagues, including key opinion leaders, were invited to complete a REDCap survey questionnaire initiated by the International Society on Thrombosis and Haemostasis Scientific and Standardisation Committee Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies.

Approach to vaccination in systemic lupus erythematosus on biological treatment.

In recent years, treat-to-target strategy and early intervention strategies with immunosuppressive agents have attempted to improve the prognosis and outcome in patients with autoimmune inflammatory rheumatic diseases. However, infectious complications due to side effects of medication remain a major concern in routine practice. In this regard, vaccine immunity and vaccination programmes are of the utmost importance in patients with systemic lupus erythematosus (SLE) in terms of morbidity and mortality.

Targeted Therapy for SLE-What Works, What Doesn't, What's Next.

For many years, the failure of randomized controlled trials (RCTs) has prevented patients with systemic lupus erythematosus (SLE) from benefiting from biological drugs that have proved to be effective in other rheumatological diseases. Only two biologics are approved for SLE, however they can only be administered to a restricted proportion of patients. Recently, several phase II RCTs have evaluated the efficacy and safety of new biologics in extra-renal SLE and lupus nephritis.

Machine learning identifies clusters of longitudinal autoantibody profiles predictive of systemic lupus erythematosus disease outcomes.

Objectives: A novel longitudinal clustering technique was applied to comprehensive autoantibody data from a large, well-characterised, multinational inception systemic lupus erythematosus (SLE) cohort to determine profiles predictive of clinical outcomes.

Methods: Demographic, clinical and serological data from 805 patients with SLE obtained within 15 months of diagnosis and at 3-year and 5-year follow-up were included. For each visit, sera were assessed for 29 antinuclear antibodies (ANA) immunofluorescence patterns and 20 autoantibodies.