brunner and lupus

OBJECTIVE: To develop a standardized steroid dosing regimen (SSR) for physicians treating childhood-onset systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN), using consensus formation methodology. METHODS: Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2). Physicians rated changes in renal and extrarenal childhood-onset SLE activity between 2 consecutive visits and proposed CS dosing (step 3)...

Canine cutaneous epitheliotropic T-cell lymphoma (CETL) and immune-mediated T-cell predominant dermatoses (IMD) share several clinical and histopathological features, but differ substantially in prognosis. The discrimination of ambiguous cases may be challenging, as diagnostic tests are limited and may prove equivocal. This study aimed to investigate transcriptional differences between CETL and IMD, as a basis for further research on discriminating diagnostic biomarkers. We performed 100bp single-end sequencing on RNA extracted from formalin-fixed and paraffin-embedded skin biopsies from dogs with CETL and IMD, respectively...

OBJECTIVE: Specific risk alleles for childhood-onset systemic lupus erythematosus SLE (cSLE) vs adult-onset SLE (aSLE) patients have not been identified. The aims of this study were to determine if there is an association (1) between non-HLA-related genetic risk score (GRS) and age of SLE diagnosis, and (2) between HLA-related GRS and age of SLE diagnosis. METHODS: Genomic DNA was obtained from 2001 multiethnic patients and genotyped using the Immunochip. Following quality control, genetic risk counting (GRCS), weighted (GRWS), standardized counting (GRSCS), and standardized weighted (GRSWS) scores were calculated based on independent single-nucleotide polymorphisms from validated SLE loci...

Follicular helper T cells (TFH ) are critical for vaccine and infection elicitation of long-lived humoral immunity, but exaggerated TFH responses can promote autoimmunity and other pathologies. It is unfortunate that no clinical interventions exist for the selective depletion of follicular T cells to alleviate these diseases. We engineered a chimeric antigen receptor (CAR) facilitating the specific targeting of cells with high expression levels of human programmed cell death protein 1 (PD-1), a cardinal feature of follicular T cells...

OBJECTIVE: To compare the diagnostic usefulness of the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for systemic lupus erythematosus (SLE) to that of the 1997 ACR classification criteria for SLE when applied to youths (age ≤21 years) with SLE. METHODS: Data were extracted from electronic health records of patients followed at a large academic pediatric hospital. The treating rheumatologist's diagnosis of SLE served as the standard criterion for identifying SLE patients (cases)...

OBJECTIVES: This ongoing Phase-2, randomised, placebo-controlled, double-blind study evaluated the efficacy, safety and pharmacokinetics of intravenous belimumab in childhood-onset systemic lupus erythematosus (cSLE). METHODS: Patients (5 to 17 years) were randomised to belimumab 10 mg/kg intravenous or placebo every 4 weeks, plus standard SLE therapy. Primary endpoint: SLE Responder Index (SRI4) response rate (Week 52). Key major secondary endpoints: proportion of patients achieving the Paediatric Rheumatology International Trials Organisation/American College of Rheumatology (PRINTO/ACR) response using 50 and '30 alternative' definitions (Week 52), and sustained response (Weeks 44 to 52) by SRI4 and Parent Global Assessment of well-being (Parent-global)...

OBJECTIVES: Long-term safety and efficacy of adalimumab among patients with juvenile idiopathic arthritis (JIA) was evaluated through 6 years of treatment. METHODS: Children aged 4-17 years with polyarticular JIA were enrolled in a phase III, randomised-withdrawal, double-blind, placebo-controlled trial consisting of a 16-week open-label lead-in period, 32-week randomised double-blind period and 360-week long-term extension. Patients were stratified by baseline methotrexate use...

BACKGROUND: To measure regional brain microvascular and microstructural changes in childhood-onset SLE (cSLE) using diffusion-weighted imaging (DWI) at multiple b values and investigate relationships of those measures with neurocognitive function and disease activity. METHODS: In this cross-sectional, case-control study, vascular volume fraction, effective diffusion, parenchymal diffusion, and blood flow parameters were regionally compared in cSLE patients and matched healthy controls...

OBJECTIVE: The importance of cold-shock Y-box binding protein 1 (YB-1) for cell homeostasis is well-documented based on prior observations of its association with certain cancer entities. This study was undertaken to explore the role of YB-1 in T cell homeostasis and survival and the potential contribution of YB-1 to the pathogenesis of systemic lupus erythematosus (SLE). METHODS: In the peripheral blood from 25 SLE patients and 25 healthy donors, the expression of YB-1 and frequency of T cell apoptosis was analyzed by quantitative polymerase chain reaction (qPCR) and fluorescence-activated cell sorting of CD4+ T cells ex vivo and also analyzed in T cells in vitro after 6 days of stimulation with anti-CD3-coupled or anti-CD3/anti-CD28-coupled microspheres...

OBJECTIVE: Initial benchmarking of childhood-onset systemic lupus erythematosus (cSLE) quality indicators revealed suboptimal performance across multiple centers. Our aim was to improve cardiovascular and bone health screenings at a tertiary treatment center for cSLE. This included annual measurements of vitamin D, lipid profiles, and bone mineral density through dual-energy x-ray absorptiometry (DXA). METHODS: Quality improvement methodology was applied to design and implement a standardized previsit planning process to electronically entered and saved orders for needed screenings prior to a scheduled clinic visit...

OBJECTIVE: Systemic lupus erythematosus (SLE) features high frequency of cardiovascular disease (CVD) and fluctuating complement levels. The clinical trial Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) aimed to evaluate whether atorvastatin treatment reduced the progression of atherosclerosis in 221 patients with childhood-onset SLE (cSLE), using carotid intima media thickness (CIMT) as surrogates. We leveraged APPLE biorepository and trial data to investigate the relationship between complement and CVD in cSLE...

PURPOSE OF REVIEW: Provide an update of studies published in last 2 years on the outcomes and therapies in childhood-onset systemic lupus erythematous (cSLE). RECENT FINDINGS: Additional evidence has been provided about the benefits of universal hydroxychloroquine in SLE patients, although antimalarial maculopathy may be more prevalent than previously thought. Recent studies support lower glucocorticoid doses than used in the past may provide comparable therapeutic benefits, and cSLE patients can mount adequate immunogenic response and sustain long-term seroprotective titers when vaccinated...

Glucocorticoids are potent anti-inflammatory and immunosuppressant medications and remain the mainstay of systemic lupus erythematosus (SLE) therapy. The potency of a specific glucocorticoid, i.e., the dose of glucocorticoid that is required to produce a specific effect, is dependent on its pharmacokinetic (PK) and pharmacodynamic (PD) properties. In this review, we summarize the PK/PD properties of commonly used glucocorticoids in an attempt to better delineate their role in the management of children with childhood-onset SLE (cSLE)...

Lupus nephritis (LN) is a common and significant manifestation, affecting 60% of adults and 80% of children with systemic lupus erythematosus, with up to 30% of patients progressing to end stage renal disease. There remains an unmet need for non-invasive markers of disease activity, damage, and response to therapy. In addition, non-invasive biomarkers that predict therapeutic efficacy are needed to enable cost-effective clinical trials of novel agents. Areas covered: This review examines the methodological aspects of urinary proteomics, the role of proteome profiling in identifying promising urinary biomarkers in LN, and the translation of research findings into clinically useful tools in the management of LN...

BACKGROUND: To develop and test the feasibility and initial effectiveness of the Treatment and Education Approach for Childhood-onset Lupus (TEACH) protocol, a 6-session cognitive behavioral therapy (CBT) intervention for adolescents and young adults (AYA) with childhood-onset systemic lupus erythematosus (cSLE). METHODS: Females with cSLE (n = 14; ages 13-19 years, M = 16.21 years) presenting to a pediatric rheumatology clinic subsequently completed the protocol, which was iteratively modified based on participant/interventionist feedback...

OBJECTIVE: To develop a Childhood Lupus Improvement Index (CHILI) as a tool to measure response to therapy in childhood-onset systemic lupus erythematosus (cSLE), with a focus on clinically relevant improvement (CRIc SLE ). METHODS: Pediatric nephrology and rheumatology subspecialists (n = 213) experienced in cSLE management were invited to define CRIc SLE and rate a total of 433 unique patient profiles for the presence/absence of CRIc SLE . Patient profiles included the following cSLE core response variables (CRVs): global assessment of patient well-being (patient-global), physician assessment of cSLE activity (MD-global), disease activity index score (here, we used the Systemic Lupus Erythematosus Disease Activity Index), urine protein-to-creatinine ratio, and Child Health Questionnaire physical summary score...

OBJECTIVE: To determine the measurement properties of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the paediatric adaptation of the Skindex29 (pSkindex27) when used in childhood-onset SLE (cSLE). METHODS: Patients with mucocutaneous involvement of cSLE were evaluated at the study entry and 6 months later. Besides the CLASI and pSkindex27, the Pediatric Quality of Life Inventory Generic Core scale (PedsQL-GC), its Rheumatology Module (PedsQL-RM), the SLE Disease Activity Index (SLEDAI) and the SLE Damage Index (SDI) were completed...

BACKGROUND: To reduce treatment variability and facilitate comparative effectiveness studies, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) published consensus treatment plans (CTPs) including one for juvenile proliferative lupus nephritis (LN). Induction immunosuppression CTPs outline treatment with either monthly intravenous (IV) cyclophosphamide (CYC) or mycophenolate mofetil (MMF) in conjunction with one of three corticosteroid (steroid) CTPs: primarily oral, primarily IV or mixed oral/IV...

Objectives: We used an unbiased proteomics approach to identify candidate urine biomarkers (CUBMs) predictive of LN chronicity and pursued their validation in a larger cohort. Methods: In this cross-sectional pilot study, we selected urine collected at kidney biopsy from 20 children with varying levels of LN damage (discovery cohort) and performed proteomic analysis using isobaric tags for relative and absolute quantification (iTRAQ). We identified differentially excreted proteins based on degree of LN chronicity and sought to distinguish markers exhibiting different relative expression patterns using hierarchically clustered log10-normalized relative abundance data with linked and distinct functions by biological network analyses...

Childhood-onset systemic lupus erythematosus (cSLE) is rare in many regions of the world, including Europe. Access to approved medications for cSLE is currently limited, among others, due to a lack of high-quality evidence from clinical trials. The objectives of the study were to evaluate the current regulatory framework regarding medication approvals, delineate barriers to clinical trial conduct, and strategies to improve access to new medications for cSLE. Relevant methodological and regulatory aspects, epidemiological data, study designs and outcome measures are reviewed, and the results of a survey among Paediatric Rheumatology International Trials Organisation/Pediatric Rheumatology Collaborative Study Group investigators are presented...