Evaluating renal disease in pediatric-onset anti-neutrophil cytoplasmic antibody-associated vasculitis: disease course, outcomes, and predictors of outcome.

Objectives: We aimed to study the disease course, outcomes, and predictors of outcome in pediatric-onset anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affecting the kidneys.

Methods: Patients eligible for this study had a diagnosis of granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or ANCA positive pauci-immune glomerulonephritis, were ≤ 18 years at diagnosis, had renal disease defined by biopsy or dialysis dependence, and had clinical data at diagnosis and either 12- or 24-months. Ambispective data from the ARChiVE/PedVas Registry was used.

Contributors to Organ Damage in Childhood Lupus: Corticosteroid Use and Disease Activity.

Background: Awareness of paediatric-specific predictors of damage in Childhood-lupus is needed to inform mitigation measures.

Objectives: To ascertain how clinical and demographic variables correlate with damage accrual and identify predictors of damage.

Methods: Analysis included UK JSLE Cohort Study participants.

Defining remission in childhood-onset lupus: PReS-endorsed consensus definitions by an international task force.

Objective: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice.

Methods: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria.

Case Report: ISG15 deficiency caused by novel variants in two families and effective treatment with Janus kinase inhibition.

ISG15 deficiency is a rare disease caused by autosomal recessive variants in the gene, which encodes the ISG15 protein. The ISG15 protein plays a dual role in both the type I and II interferon (IFN) immune pathways. Extracellularly, the ISG15 protein is essential for IFN-γ-dependent anti-mycobacterial immunity, while intracellularly, ISG15 is necessary for USP18-mediated downregulation of IFN-α/β signalling.

Genetic testing of Behçet's disease using next-generation sequencing to identify monogenic mimics and HLA-B*51.

Objective: Several monogenic autoinflammatory disorders and primary immunodeficiencies can present early in life with features that may be mistaken for Behçet's disease (BD). We aimed to develop a genetic analysis workflow to identify rare monogenic BD-like diseases and establish the contribution of HLA haplotype in a cohort of patients from the UK.

Methods: Patients with clinically suspected BD were recruited from four BD specialist care centres in the UK.

PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS).

Objective: To achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials.

Methods: The International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria.

Results: The Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS).

PSTPIP1-associated myeloid-related proteinaemia inflammatory (PAMI) syndrome; a case presenting as a perinatal event with early central nervous system involvement?

Background: We report a three-year-old girl with a potentially unique phenotype of perinatal onset and neurovascular features who was found to have PAMI syndrome. We also compare her case to those previously reported and review the differences between the PSTPIP1-associated inflammatory diseases (PAID) phenotypes and genotypes.

Case Presentation: The patient was found to have a heterozygous pathogenic variant in PSTPIP1 (c.

Panel sequencing links rare, likely damaging gene variants with distinct clinical phenotypes and outcomes in juvenile-onset SLE.

Objectives: Juvenile-onset systemic lupus erythematosus (jSLE) affects 15-20% of lupus patients. Clinical heterogeneity between racial groups, age groups and individual patients suggests variable pathophysiology. This study aimed to identify highly penetrant damaging mutations in genes associated with SLE/SLE-like disease in a large national cohort (UK JSLE Cohort Study) and compare demographic, clinical and laboratory features in patient sub-cohorts with 'genetic' SLE vs remaining SLE patients.

Wide variation in glucocorticoid dosing in paediatric ANCA-associated vasculitis with renal disease: a paediatric vasculitis initiative study.

Objectives: High-dose glucocorticoids for remission-induction of ANCA-associated vasculitis are recommended and commonly used in adults, but recent studies suggest lower glucocorticoid doses can reduce toxicity without reducing efficacy. No paediatric-specific data exists to inform optimal glucocorticoid dosing in paediatric ANCA-associated vasculitis (pAAV). Our objectives were to describe glucocorticoid use in pAAV-related renal disease, and to explore associations between glucocorticoid dose, baseline patient characteristics and 12-month outcomes.

Attainment of low disease activity and remission targets reduces the risk of severe flare and new damage in childhood lupus.

Objectives: To assess the achievability and effect of attaining low disease activity (LDA) or remission in childhood-onset SLE (cSLE).

Methods: Attainment of three adult-SLE derived definitions of LDA (LLDAS, LA, Toronto-LDA), and four definitions of remission (clinical-SLEDAI-defined remission on/off treatment, pBILAG-defined remission on/off treatment) was assessed in UK JSLE Cohort Study patients longitudinally. Prentice-Williams-Petersen gap recurrent event models assessed the impact of LDA/remission attainment on severe flare/new damage.

Juvenile Dermatomyositis Magnetic Resonance Imaging Score (JIS) does not correlate with criteria for clinically inactive disease: a single-centre retrospective evaluation.

The Paediatric Rheumatology International Trials Organisation (PRINTO) criteria for clinically inactive disease (CID) and their proposal for glucocorticoid tapering do not consider MRI findings, despite the growing use of MRI and development of reliable MRI scoring tools. We aim to evaluate how CID correlates with MRI scores and physician decision making. We retrospectively used the Juvenile Dermatomyositis Imaging Score (JIS) to score MRIs of all children with JDM over a 10-year period.

The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery.

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells, with increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated immune features including increased monocyte CD163 levels, emergence of a new population of immature neutrophils and, in some patients, transiently increased plasma arginase.

Neuropsychiatric involvement in juvenile-onset systemic lupus erythematosus: Data from the UK Juvenile-onset systemic lupus erythematosus cohort study.

Introduction: Juvenile-onset systemic lupus erythematosus (JSLE) is a rare autoimmune/inflammatory disease with significant morbidity and mortality. Neuropsychiatric (NP) involvement is a severe complication, encompassing a heterogeneous range of neurological and psychiatric manifestations.

Methods: Demographic, clinical, and laboratory features of NP-SLE were assessed in participants of the UK JSLE Cohort Study, and compared to patients in the same cohort without NP manifestations.

Vitamin D status of children with paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS).

Coronavirus disease 2019 (COVID-19) has caused mild illness in children, until the emergence of the novel hyperinflammatory condition paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS). PIMS-TS is thought to be a post-SARS-CoV-2 immune dysregulation with excessive inflammatory cytokine release. We studied 25 hydroxyvitamin D (25OHD) concentrations in children with PIMS-TS, admitted to a tertiary paediatric hospital in the UK, due to its postulated role in cytokine regulation and immune response.

Limited sensitivity and specificity of the ACR/EULAR-2019 classification criteria for SLE in JSLE?-observations from the UK JSLE Cohort Study.

Objectives: This study aimed to test the performance of the new ACR and EULAR criteria, that include ANA positivity as entry criterion, in JSLE.

Methods: Performance of the ACR/EULAR-2019 criteria were compared with Systemic Lupus International Collaborating Clinics (SLICC-2012), using data from children and young people (CYP) in the UK JSLE Cohort Study (n = 482), with the ACR-1997 criteria used as reference standard. An unselected cohort of CYP positive for ANA (n = 129) was used to calculate positive/negative predictive values of the criteria.

'It is good to have a target in mind': qualitative views of patients and parents informing a treat to target clinical trial in juvenile-onset systemic lupus erythematosus.

Objective: We sought to explore patient and parental views on treatment targets, outcome measures and study designs being considered for a future JSLE treat-to-target (T2T) study.

Methods: We conducted topic-guided, semistructured interviews with JSLE patients and parents and analysed the audio recorded interviews using thematic approaches.

Results: Patients and parents differed regarding symptoms they felt would be tolerable, representing 'low disease activity'.

Anti-tumour necrosis factor treatment for the prevention of ischaemic events in patients with deficiency of adenosine deaminase 2 (DADA2).

Objective: To evaluate the impact of anti-Tumour Necrosis Factor-α (anti-TNF) treatment on the occurrence of vasculitic ischaemic events in patients with deficiency of adenosine deaminase 2 (DADA2).

Methods: A retrospective analysis of DADA2 patients referred from six centres to Great Ormond Street Hospital for Children was conducted. Ischaemic events, vasculitic disease activity, biochemical, immunological, and radiological features were compared, before and after anti-TNF treatment.

Clinical and laboratory phenotypes in juvenile-onset Systemic Lupus Erythematosus across ethnicities in the UK.

Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease. Patients diagnosed with juvenile-onset SLE (jSLE), when compared to individuals with adult-onset SLE, develop more severe organ involvement, increased disease activity and greater tissue and organ damage. In adult-onset SLE, clinical characteristics, pathomechanisms, disease progression and outcomes do not only vary between individuals and age groups, but also ethnicities.

Critical Care Course of Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 and Response to Immunomodulation.

We describe the critical care course of children with a novel hyperinflammatory syndrome associated with coronavirus disease 2019 (COVID-19) pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with focus on trajectory before and after immunomodulation. Overall, 10 patients who met the U.K.