Altered Purinergic Signaling and CD8+ T Cell Dysregulation in STAT3 GOF Syndrome.

Signal transduction downstream of activating stimuli controls CD8+ T cell biology, however these external inputs can become uncoupled from transcriptional regulation in Primary Immune Regulatory Disorders (PIRDs). Gain-of-function (GOF) variants in STAT3 amplify cytokine signaling and cause a severe PIRD characterized by early onset autoimmunity, lymphoproliferation, recurrent infections, and immune dysregulation. In both primary human and mouse models of STAT3 GOF, CD8+ T cells have been implicated as pathogenic drivers of autoimmunity.

Evaluating a Child Presenting with Symptoms Concerning for Sjögren Disease: A Clinical Tool for Practice.

Background/purpose: Childhood Sjögren disease (cSjD) is a rare disease. There are no widely accepted diagnostic or classification criteria for cSjD. To fill this gap, members from CARRA Sjogren Workgroup and the International cSjD Workgroup created a clinical diagnostic algorithm.

The Florida Scoring System for stratifying children with suspected Sjögren's disease: a cross-sectional machine learning study.

Background: Childhood Sjögren's disease is a rare, underdiagnosed, and poorly-understood condition. By integrating machine learning models on a paediatric cohort in the USA, we aimed to develop a novel system (the Florida Scoring System) for stratifying symptomatic paediatric patients with suspected Sjögren's disease.

Methods: This cross-sectional study was done in symptomatic patients who visited the Department of Pediatric Rheumatology at the University of Florida, FL, USA.

Single-cell transcriptomics unveil profiles and interplay of immune subsets in rare autoimmune childhood Sjögren's disease.

Childhood Sjögren's disease represents critically unmet medical needs due to a complete lack of immunological and molecular characterizations. This study presents key immune cell subsets and their interactions in the periphery in childhood Sjögren's disease. Here we show that single-cell RNA sequencing identifies the subsets of IFN gene-enriched monocytes, CD4 T effector memory, and XCL1 NK cells as potential key players in childhood Sjögren's disease, and especially in those with recurrent parotitis, which is the chief symptom prompting clinical visits from young children.

Long-term efficacy of sialendoscopy in treating childhood Sjögren's disease with chronological monitoring by salivary gland ultrasonography: A novel approach.

Background: Childhood Sjögren's Disease (cSjD) is an underdiagnosed phenomenon with clinical and pathophysiological nuances in contrast to Sjögren's Disease (SjD) in the adult population. While adults typically experience sicca symptoms, children with cSjD often present with recurrent parotitis, diverse autoantibody profiles, and renal and neurological manifestations. Diagnosis and classification in pediatric rheumatology remain controversial due to the reliance on adult-focused diagnostic criteria and the lack of standardized treatment and understanding of outcomes.

Bortezomib is efficacious in the treatment of severe childhood-onset neuropsychiatric systemic lupus erythematosus with psychosis: a case series and mini-review of B-cell immunomodulation in antibody-mediated diseases.

Childhood-onset neuropsychiatric systemic lupus erythematosus (cNPSLE) with psychosis is a challenging manifestation of SLE. Pathogenic long-lived plasma cells (LLPCs) are not specifically targeted by standard immunosuppression and their persistence contributes to chronic autoimmunity. Bortezomib is approved for the treatment of multiple myeloma and has shown benefits in a variety of other antibody-mediated diseases.

An ELF4 hypomorphic variant results in NK cell deficiency.

NK cell deficiencies (NKD) are a type of primary immune deficiency in which the major immunologic abnormality affects NK cell number, maturity, or function. Since NK cells contribute to immune defense against virally infected cells, patients with NKD experience higher susceptibility to chronic, recurrent, and fatal viral infections. An individual with recurrent viral infections and mild hypogammaglobulinemia was identified to have an X-linked damaging variant in the transcription factor gene ELF4.

Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome.

Background: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity.

Objective: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants.

Methods: We identified 191 patients from 33 countries with 72 unique mutations.

Reliability of the Pediatric Specific Musculoskeletal Ultrasound Scoring Systems for the Elbow, Wrist, and Finger Joints.

Objective: Musculoskeletal ultrasound (MSUS) is increasingly being used in the evaluation of pediatric musculoskeletal diseases. In order to provide objective assessments of arthritis, reliable MSUS scoring systems are needed. Recently, joint-specific scoring systems for arthritis of the pediatric elbow, wrist, and finger joints were proposed by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) MSUS workgroup.

A human STAT3 gain-of-function variant confers T cell dysregulation without predominant Treg dysfunction in mice.

Primary immune regulatory disorders (PIRD) represent a group of disorders characterized by immune dysregulation, presenting with a wide range of clinical disease, including autoimmunity, autoinflammation, or lymphoproliferation. Autosomal dominant germline gain-of-function (GOF) variants in STAT3 result in a PIRD with a broad clinical spectrum. Studies in patients have documented a decreased frequency of FOXP3+ Tregs and an increased frequency of Th17 cells in some patients with active disease.

The Diagnostic Performance of Early Sjögren's Syndrome Autoantibodies in Juvenile Sjögren's Syndrome: The University of Florida Pediatric Cohort Study.

Objectives: The aim of this study was to evaluate the clinical validity of early Sjögren's syndrome (SS) autoantibodies (eSjA), which were originally marketed for early diagnosis of SS, for juvenile SS (JSS) in a recently identified pediatric cohort.

Methods: A total of 105 symptomatic subjects with eSjA results available were evaluated at the Center for Orphaned Autoimmune Disorders at the University of Florida and enrolled for this study. JSS diagnosis was based on the 2016 ACR/EULAR SS criteria.

Takayasu's arteritis presenting as acute myocardial infarction: case series and review of literature.

This series describes three adolescent females who presented with chest pain and ventricular dysfunction related to acute coronary ischemia secondary to Takayasu's arteritis with varied courses of disease progression leading to a diverse range of therapies including cardiac transplantation. While Takayasu's arteritis is rare in childhood, it should be strongly considered in any adolescent female presenting with systemic inflammation and chest pain consistent with myocardial infarction. A high index of suspicion can lead to early detection and aggressive management of the underlying vasculitis reducing associated morbidity and mortality.

Pulmonary Histopathology Findings in Patients With STAT3 Gain of Function Syndrome.

Introduction And Aim: Multiorgan autoimmunity and interstitial lung disease (ILD) are reported in patients with STAT3 GOF syndrome.

Results: We present lung histopathology findings in 3 such children, two of whom underwent wedge biopsies with adequate diagnostic material. Wedge biopsies showed interstitial cellular expansion with linear and nodular aggregates of CD8 positive T lymphocytes, plasma cells, and histiocytes; consistent with lymphocytic interstitial pneumonia pattern (LIP).

Childhood Sjögren syndrome: features of an international cohort and application of the 2016 ACR/EULAR classification criteria.

Objective: Sjögren syndrome in children is a poorly understood autoimmune disease. We aimed to describe the clinical and diagnostic features of children diagnosed with Sjögren syndrome and explore how the 2016 ACR/EULAR classification criteria apply to this population.

Methods: An international workgroup retrospectively collected cases of Sjögren syndrome diagnosed under 18 years of age from 23 centres across eight nations.

Consensus treatment plans for periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA): a framework to evaluate treatment responses from the childhood arthritis and rheumatology research alliance (CARRA) PFAPA work group.

Background: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. There is considerable heterogeneity in management strategies and a lack of evidence-based treatment guidelines. Consensus treatment plans (CTPs) are standardized treatment regimens that are derived based upon best available evidence and current treatment practices that are a way to enable comparative effectiveness studies to identify optimal therapy and are less costly to execute than randomized, double blind placebo controlled trials.

Juvenile Sjögren's Syndrome: Clinical Characteristics With Focus on Salivary Gland Ultrasonography.

Objective: Juvenile Sjögren's syndrome (SS) is a rare, poorly defined, and possibly underdiagnosed condition affecting children and adolescents. The aim of this study was to characterize symptoms and clinical findings of juvenile SS and to explore the clinical application of major salivary gland ultrasonography (SGUS) in patients with juvenile SS.

Methods: A cross-sectional multicenter study recruited patients with disease onset until age 18 years (n = 67).

Novel Ultrasound Image Acquisition Protocol and Scoring System for the Pediatric Knee.

Objective: The use of musculoskeletal ultrasound is increasing among pediatric rheumatologists. Reliable scoring systems are needed for the objective assessment of synovitis. The aims of this study were to create a standardized and reproducible image acquisition protocol for B-mode and Doppler ultrasound of the pediatric knee, and to develop a standardized scoring system and determine its reliability for pediatric knee synovitis.

S100A12 and S100A8/9 proteins are biomarkers of articular disease activity in Blau syndrome.

Objective: To identify biomarkers of articular and ocular disease activity in patients with Blau syndrome (BS).

Methods: Multiplex plasma protein arrays were performed in five BS patients and eight normal healthy volunteers (NHVs). Plasma S100A12 and S100A8/9 were subsequently measured by ELISA at baseline and 1-year follow-up in all patients from a prospective multicentre cohort study.

Recurrent cardiac tamponade in a child with newly diagnosed systemic-onset juvenile idiopathic arthritis.

A previously healthy 5-year-old boy presented with prolonged fever, evanescent rash, and arthralgias. Diagnostic tests were significant for marked systemic inflammation. He rapidly developed pleural and pericardial effusions with cardiac tamponade, requiring placement of a pericardial drain.