Discordant Perception of Disease Activity Between Providers and Adolescents with Systemic Lupus Erythematosus: A Cohort Study.

Discordance in perception of disease activity between adolescent patients with lupus and their providers may influence disease outcomes. We found that patients endorsed higher perceptions of disease activity than providers. Discordance was present at all levels of disease activity, particularly in patients with high activity, nephritis, and/or taking corticosteroids or mycophenolate mofetil.

Renal Response Outcomes of the EuroLupus and National Institutes of Health Cyclophosphamide Dosing Regimens in Childhood-Onset Proliferative Lupus Nephritis.

Objective: We compared clinical characteristics and renal response in patients with childhood-onset proliferative lupus nephritis (LN) treated with the EuroLupus versus National Institutes of Health (NIH) cyclophosphamide (CYC) regimen.

Methods: A retrospective cohort study was conducted at 11 pediatric centers in North America that reported using both CYC regimens. Data were extracted from the electronic medical record at baseline and 3, 6, and 12 months after treatment initiation with CYC.

B lymphocytes in treatment-naive paediatric patients with lupus are epigenetically distinct from healthy children.

Background: SLE is likely triggered by gene-environment interactions. We have shown that most SLE-associated haplotypes encompass genomic regions enriched for epigenetic marks associated with enhancer function in lymphocytes, suggesting genetic risk is exerted through altered gene regulation. Data remain scarce on how epigenetic variance contributes to disease risk in paediatric SLE (pSLE).

The safety of COVID-19 vaccination in immunocompromised children and young adults with immune-mediated inflammatory disease.

Aim: To assess safety of COVID-19 vaccination in paediatric patients with immune-mediated inflammatory disease (IMID).

Methods: Subjects of 5-21 years of age with IMID who received at least one COVID-19 vaccine completed electronic surveys after each vaccine to assess side effects within 1 week of vaccination, current medications and COVID-19 testing after vaccination. Charts were reviewed for COVID-19 polymerase chain reaction and IgG response to SARS-CoV-2 spike protein results and for disease flare during the study period.

Seroprevalence and clinical outcomes of SARS-CoV-2 in paediatric patients with rheumatic disease.

Objectives: Immunosuppressed paediatric patients with rheumatic disease (RD) may be at risk for severe or critical disease related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data remain scarce on coronavirus disease 2019 (COVID-19) outcomes in paediatric RD patients. The aim of this study was to determine the seroprevalence of SARS-CoV-2 IgG and to describe COVID-19 outcomes in immunosuppressed paediatric RD patients.

Differences in Healthcare Transition Views, Practices, and Barriers Among North American Pediatric Rheumatology Clinicians From 2010 to 2018.

Objective: Since 2010, the rheumatology community has developed guidelines and tools to improve healthcare transition. In this study, we aimed to compare current transition practices and beliefs among Childhood Arthritis and Rheumatology Research Alliance (CARRA) rheumatology providers with transition practices from a provider survey published in 2010.

Methods: In 2018, CARRA members completed a 25-item online survey about healthcare transition.

Emerging B-Cell Therapies in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease of unknown etiology, whose hallmark is the production of autoantibodies. B cells are promising targets for novel SLE therapies. In 2011, belimumab (Benlysta), a fully humanized monoclonal antibody inhibiting B-cell activation and proliferation, was the first medication in 50 years to be approved by the US Food and Drug Administration to treat adult SLE.

Performance and psychometric properties of lupus impact tracker in assessing patient-reported outcomes in pediatric lupus: Report from a pilot study.

Objective: To evaluate the reliability, validity, feasibility and psychometric performance of the Lupus Impact Tracker (LIT) as a patient reported outcome (PRO) measure tool in pediatric systemic lupus erythematosus (pSLE).

Methods: This is a prospective, observational, pilot study where patients aged between 12 and 25 years, fulfilling the 1997 ACR classification criteria for SLE, were enrolled. Over 3 consecutive, routine, clinical visits, the patients completed the LIT alongside the Patient-Reported Outcomes Measurement Information System-Short Forms (PROMIS-SFs), Childhood Health Assessment Questionnaire (CHAQ).

Management of Pediatric Systemic Lupus Erythematosus: Focus on Belimumab.

Belimumab (Benlysta) is a fully humanized monoclonal antibody that inhibits B lymphocyte stimulator (BLyS, also known as B cell-activating factor of the tumor necrosis factor family) and was approved by the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency for the treatment of autoantibody-positive systemic lupus erythematosus (SLE) in adults with moderate disease activity. Belimumab was recently FDA approved for use in children with SLE between 5 and 17 years of age. This review discusses the key findings of the belimumab phase III trials in adult SLE (via intravenous and subcutaneous administrations), phase II trial in pediatric SLE (intravenous administration), and post hoc analyses.

Prevalence of progressive multifocal leukoencephalopathy (PML) in adults and children with systemic lupus erythematosus.

Objective: To define the risk of progressive multifocal leukoencephalopathy (PML) in SLE.

Methods: This is a retrospective observational study to evaluate PML cases in patients with SLE admitted to two large academic hospitals. Using electronic medical record (EMR) data, International Classification of Diseases (ICD) codes identified PML cases among patients with SLE, rheumatoid arthritis (RA) (controls), had renal transplant and with HIV.

Validation of the 2019 European League Against Rheumatism/American College of Rheumatology Criteria Compared to the 1997 American College of Rheumatology Criteria and the 2012 Systemic Lupus International Collaborating Clinics Criteria in Pediatric Systemic Lupus Erythematosus.

Objective: Different classification criteria for systemic lupus erythematosus (SLE) have been proposed for many years. The most widely used and accepted criteria has been the 1997 American College of Rheumatology (ACR) criteria. In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) criteria were published in an attempt to improve the clinical relevance of SLE criteria.

Chromatin landscapes and genetic risk in systemic lupus.

Background: Systemic lupus erythematosus (SLE) is a multi-system, complex disease in which the environment interacts with inherited genes to produce broad phenotypes with inter-individual variability. Of 46 single nucleotide polymorphisms (SNPs) shown to confer genetic risk for SLE in recent genome-wide association studies, 30 lie within noncoding regions of the human genome. We therefore sought to identify and describe the functional elements (aside from genes) located within these regions of interest.

Proceedings of the 2016 Childhood Arthritis and Rheumatology Research Alliance (CARRA) Scientific Meeting : Toronto, Canada. 14-17 April 2016.

P1 Serologic evidence of gut-driven systemic inflammation in juvenile idiopathic arthritis Lampros Fotis, Nur Shaikh, Kevin Baszis, Anthony French, Phillip Tarr P2 Oral health and anti-citrullinated peptide antibodies (ACPA) in juvenile idiopathic arthritis Sriharsha Grevich, Peggy Lee, Sarah Ringold, Brian Leroux, Hannah Leahey, Megan Yuasa, Jessica Foster, Jeremy Sokolove, Lauren Lahey, William Robinson, Joshua Newsom, Anne Stevens P3 Novel autoantigens for endothelial cell antibodies in pediatric rheumatic diseases identified by proteomics Rie Karasawa, Mayumi Tamaki, Megumi Tanaka, Toshiko Sato, Kazuo Yudoh, James N. Jarvis P4 Transcriptional profiling reveals monocyte signature associated with JIA patient poor response to methotrexate Halima Moncrieffe, Mark F. Bennett, Monica Tsoras, Lorie Luyrink, Huan Xu, Sampath Prahalad, Paula Morris, Jason Dare, Peter A.

Use of Glucuronidated Mycophenolic Acid Levels for Therapeutic Monitoring in Pediatric Lupus Nephritis Patients.

Background/objectives: Mycophenolate mofetil (MMF) is used to treat pediatric-onset lupus nephritis (pLN). Data are equivocal on the use of plasma mycophenolic acid (MPA) levels as a measure of efficacy and predictor of therapeutic outcomes in pLN. Glucuronidated MPA (MPA-G) is an inactive metabolite that is a marker of adequate absorption and normal metabolism of MMF.

Safety and Efficacy of Belimumab to Treat Systemic Lupus Erythematosus in Academic Clinical Practices.

Objective: To evaluate the use and efficacy of belimumab in academic practices. Belimumab is a human monoclonal antibody that inhibits soluble B lymphocyte stimulator and has been approved for the treatment of adults with systemic lupus erythematosus (SLE).

Methods: Invitations to participate and complete a 1-page questionnaire for each patient prescribed belimumab were sent to 16 physicians experienced in SLE phase III clinical trials.

Belimumab in systemic lupus erythematosus: a perspective review.

Belimumab (Benlysta(®)) is a fully humanized monoclonal antibody that inhibits B-lymphocyte stimulator (also known as B cell activating factor of the tumor necrosis factor family) and was approved by the US Food and Drug Administration and the European Medicines Evaluation Agency for treatment of autoantibody-positive systemic lupus erythematosus (SLE) in adults. This review discusses the key findings of the phase III trials, post hoc analyses, and real-world postmarketing use of belimumab in the routine care of SLE patients. It also highlights the safety profile of belimumab and gives insight into its potential use to treat childhood-onset SLE.

Adrenocorticotropic hormone gel in the treatment of systemic lupus erythematosus: A retrospective study of patients.

Objectives: Acthar Gel is a long-acting formulation of adrenocorticotropic hormone (ACTH) with anti-inflammatory effects thought to be mediated in part through melanocortin receptor activation. This study was initiated to understand the role of Acthar Gel in SLE treatment in rheumatology practices.

Methods: This is a retrospective case series of nine adult female patients treated with Acthar Gel for at least six months at five academic centers.

Case Report: Group B Streptococcus meningitis in an adolescent .

Streptococcus agalactiae (group B Streptococcus, GBS) usually colonizes the gastrointestinal and lower genital tracts of asymptomatic hosts, yet the incidence of invasive disease is on the rise . We describe a case of an 18 year old woman, recently diagnosed with lupus, who reported a spontaneous abortion six weeks prior to her hospitalization.  She presented with fever, altered mental status, and meningeal signs, paired with a positive blood culture for GBS.

STAT3 interrupts ATR-Chk1 signaling to allow oncovirus-mediated cell proliferation.

DNA damage response (DDR) is a signaling network that senses DNA damage and activates response pathways to coordinate cell-cycle progression and DNA repair. Thus, DDR is critical for maintenance of genome stability, and presents a powerful defense against tumorigenesis. Therefore, to drive cell-proliferation and transformation, viral and cellular oncogenes need to circumvent DDR-induced cell-cycle checkpoints.

Human B cell immortalization for monoclonal antibody production.

Infection of primary B lymphocytes with Epstein-Barr virus gives rise to growth-transformed and immortalized lymphoblastoid cell lines (LCL) in vitro. Among their many applications is the use of LCL to present antigens in a variety of immunologic assays and to generate human monoclonal antibodies. This chapter describes a method to generate LCL from donor peripheral blood with rapid immortalization and cryopreservation times.

Establishment of Epstein-Barr virus growth-transformed lymphoblastoid cell lines.

Infection of B cells with Epstein-Barr virus (EBV) leads to proliferation and subsequent immortalization, resulting in establishment of lymphoblastoid cell lines (LCL) in vitro. Since LCL are latently infected with EBV, they provide a model system to investigate EBV latency and virus-driven B cell proliferation and tumorigenesis(1). LCL have been used to present antigens in a variety of immunologic assays(2, 3).

TNF-alpha is necessary for induction of coronary artery inflammation and aneurysm formation in an animal model of Kawasaki disease.

Kawasaki disease is the most common cause of multisystem vasculitis in childhood. The resultant coronary artery lesions make Kawasaki disease the leading cause of acquired heart disease in children in the developed world. TNF-alpha is a pleiotropic inflammatory cytokine elevated during the acute phase of Kawasaki disease.