Active Vibrational Achilles Tendon Sensing for Identifying and Characterizing Inflammatory Symptomatology in Enthesitis Related Arthritis.

Objective: This study explores the potential of active vibrational sensing as a digital biomarker to identify and characterize inflammatory symptomatology in the Achilles tendon and its entheses in juvenile idiopathic arthritis (JIA), particularly enthesitis related arthritis (ERA), a subcategory of JIA.

Methods: Active vibrational data were non-invasively recorded using a miniature coin vibration motor and accelerometer. Twenty active vibration recordings from children diagnosed with JIA were used in the analysis.

The Simple prEservatioN of Single cElls method for cryopreservation enables the generation of single-cell immune profiles from whole blood.

Introduction: Current multistep methods utilized for preparing and cryopreserving single-cell suspensions from blood samples for single-cell RNA sequencing (scRNA-seq) are time-consuming, requiring trained personnel and special equipment, so limiting their clinical adoption. We developed a method, Simple prEservatioN of Single cElls (SENSE), for single-step cryopreservation of whole blood (WB) along with granulocyte depletion during single-cell assay, to generate high quality single-cell profiles (SCP).

Methods: WB was cryopreserved using the SENSE method and peripheral blood mononuclear cells (PBMCs) were isolated and cryopreserved using the traditional density-gradient method (PBMC method) from the same blood sample (n=6).

Prevalence of tissue transglutaminase antibodies and IgA deficiency are not increased in juvenile idiopathic arthritis: a case-control study.

Background: The prevalence of Celiac Disease (CD) in Juvenile Idiopathic Arthritis (JIA) has been reported to be 0.1-7% in various small studies. As a result of the limited number of research and their inconclusive results there are no clear recommendations for routine CD screening in asymptomatic patients with JIA.

Knee acoustic emissions as a noninvasive biomarker of articular health in patients with juvenile idiopathic arthritis: a clinical validation in an extended study population.

Background: Joint acoustic emissions from knees have been evaluated as a convenient, non-invasive digital biomarker of inflammatory knee involvement in a small cohort of children with Juvenile Idiopathic Arthritis (JIA). The objective of the present study was to validate this in a larger cohort.

Findings: A total of 116 subjects (86 JIA and 30 healthy controls) participated in this study.

Profiling the peripheral immune response to ex vivo TNF stimulation in untreated juvenile idiopathic arthritis using single cell RNA sequencing.

Background: Juvenile Idiopathic Arthritis (JIA) is an autoimmune disease with a heterogenous clinical presentation and unpredictable response to available therapies. This personalized transcriptomics study sought proof-of-concept for single-cell RNA sequencing to characterize patient-specific immune profiles.

Methods: Whole blood samples from six untreated children, newly diagnosed with JIA, and two healthy controls were cultured for 24 h with or without ex vivo TNF stimulation and subjected to scRNAseq to examine cellular populations and transcript expression in PBMCs.

Clinical Determinants of Childhood Onset Systemic Lupus Erythematosus among Early and Peri-Adolescent Age Groups.

Introduction: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that is associated with significant morbidity and mortality. SLE disproportionately affects women and minorities. Childhood-onset SLE (cSLE) in particular tends to be more aggressive than adult-onset SLE.

Immunometabolic Analysis of Synovial Fluid from Juvenile Idiopathic Arthritis Patients.

Juvenile idiopathic arthritis (JIA) is an inflammatory rheumatic disorder. Polymorphonuclear neutrophils (PMNs) are present in JIA synovial fluid (SF), but with variable frequency. SF PMNs in JIA were previously shown to display high exocytic but low phagocytic and immunoregulatory activities.

Quality of life measures and physical activity in childhood systemic lupus erythematosus.

Childhood systemic lupus erythematosus (cSLE) is a life-long disease with significant morbidity and mortality, and with associated significant impact on health-related quality of life (HRQOL). Previous literature supports that physical activity has positive impact on HRQOL in patients with chronic diseases, including cSLE. We sought to describe the physical activity of our patients with cSLE and determine the relationship between physical activity, SLE activity, treatment modalities and HRQOL in cSLE.

Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH).

Background: Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening sequela of severe acute respiratory syndrome coronavirus 2 infection characterized by hyperinflammation and multiorgan dysfunction. Although hyperinflammation is a prominent manifestation of MIS-C, there is limited understanding of how the inflammatory state of MIS-C differs from that of well-characterized hyperinflammatory syndromes such as hemophagocytic lymphohistiocytosis (HLH).

Objectives: We sought to compare the qualitative and quantitative inflammatory profile differences between patients with MIS-C, coronavirus disease 2019, and HLH.

Knee Acoustic Emissions as a Digital Biomarker of Disease Status in Juvenile Idiopathic Arthritis.

In this paper, we quantify the joint acoustic emissions (JAEs) from the knees of children with juvenile idiopathic arthritis (JIA) and support their use as a novel biomarker of the disease. JIA is the most common rheumatic disease of childhood; it has a highly variable presentation, and few reliable biomarkers which makes diagnosis and personalization of care difficult. The knee is the most commonly affected joint with hallmark synovitis and inflammation that can extend to damage the underlying cartilage and bone.

Impact of the Season of Birth on the Development of Juvenile Idiopathic Arthritis in the United States: A Nationwide Registry-based Study.

Objective: Autoimmune disorders result from the interplay of genetic and environmental factors. Many autoimmune disorders are associated with specific seasons of birth, implicating a role for environmental determinants in their etiopathology. We investigated if there is an association between the season of birth and the development of juvenile idiopathic arthritis (JIA).

Acoustic Emissions From Loaded and Unloaded Knees to Assess Joint Health in Patients With Juvenile Idiopathic Arthritis.

Objective: We studied and compared joint acoustical emissions (JAEs) in loaded and unloaded knees as digital biomarkers for evaluating knee health status during the course of treatment in patients with juvenile idiopathic arthritis (JIA).

Methods: JAEs were recorded from 38 participants, performing 10 repetitions of unloaded flexion/extension (FE) and loaded squat exercises. A novel algorithm was developed to detect and exclude rubbing noise and loose microphone artifacts from the signals, and then 72 features were extracted.

Using Knee Acoustical Emissions for Sensing Joint Health in Patients with Juvenile Idiopathic Arthritis: A Pilot Study.

In this paper, we present a pilot study evaluating novel methods for assessing joint health in patients with Juvenile Idiopathic Arthritis (JIA) using wearable acoustical emission measurements from the knees. Measurements were taken from four control subjects with no known knee injuries, and from four subjects with JIA, before and after treatment. Time and frequency domain features were extracted from the acoustical emission signals and used to compute a knee audio score.

Disease-specific regulation of gene expression in a comparative analysis of juvenile idiopathic arthritis and inflammatory bowel disease.

Background: The genetic and immunological factors that contribute to differences in susceptibility and progression between sub-types of inflammatory and autoimmune diseases continue to be elucidated. Inflammatory bowel disease and juvenile idiopathic arthritis are both clinically heterogeneous and known to be due in part to abnormal regulation of gene activity in diverse immune cell types. Comparative genomic analysis of these conditions is expected to reveal differences in underlying genetic mechanisms of disease.

Case-control Association Study of Autoimmunity Associated Variants in PDCD1 and Juvenile Idiopathic Arthritis.

Purpose: Variants in the gene encoding Programmed Cell Death-1 (PDCD1) have been associated with susceptibility to Systemic Lupus Erythematosus and other autoimmune diseases. Given that clinically distinct autoimmune phenotypes share common genetic susceptibility factors, variants in PDCD-1 were tested for a possible association with Juvenile Idiopathic Arthritis (JIA).

Methods: Four Single Nucleotide Polymorphisms (SNPS) in the PDCD1 gene were genotyped and analyzed: rs7421861, rs11568821, rs10204525, and rs7568402 in 834 cases and 855 controls of Northern European ancestry.

Familial autoimmunity in the Childhood Arthritis and Rheumatology Research Alliance registry.

Background: Clinically distinct autoimmune phenotypes share genetic susceptibility factors. We investigated the prevalence of familial autoimmunity among subjects with juvenile idiopathic arthritis (JIA), childhood systemic lupus erythematosus (cSLE) and juvenile dermatomyositis (JDM) in the CARRA Registry, the largest multicenter observational Registry for pediatric rheumatic disease.

Methods: Children with JIA, cSLE and JDM enrolled in the CARRA Registry between May 2010 and May 2012 were investigated for differences in proportion of subjects who had first-degree relatives (FDR) with autoimmunity.

Phenotypic Characterization of Juvenile Idiopathic Arthritis in African American Children.

Objective: Juvenile idiopathic arthritis (JIA) affects children of all races. Prior studies suggest that phenotypic features of JIA in African American (AA) children differ from those of non-Hispanic white (NHW) children. We evaluated the phenotypic differences at presentation between AA and NHW children enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, and replicated the findings in a JIA cohort from a large center in the southeastern United States.

Symptoms of periodontitis and antibody responses to Porphyromonas gingivalis in juvenile idiopathic arthritis.

Background: The association between rheumatoid arthritis (RA) and periodontitis is well established. Some children with juvenile idiopathic arthritis (JIA) phenotypically resemble adults with RA, characterized by the presence of anti-cyclic citrullinated peptide (CCP) antibodies. We sought to investigate an association between CCP-positive JIA and symptoms of periodontitis and antibodies to oral microbiota.

Limitations in the classification of childhood-onset rheumatoid arthritis.

Objective: Rheumatoid factor-positive polyarthritis (RF+ poly) is the juvenile idiopathic arthritis (JIA) category that resembles adult seropositive rheumatoid arthritis (RA). We studied children with RF+ and/or anticyclic citrullinated peptide antibody (anti-CCP)+ JIA to determine what proportion of those children meet International League of Associations for Rheumatology (ILAR) criteria for RF+ poly JIA and to assess for significant differences between children who meet RF+ poly criteria and those who are classified in other categories.

Methods: Charts of children with JIA who were RF+ and/or anti-CCP+ were reviewed.

Risk markers of juvenile idiopathic arthritis-associated uveitis in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry.

Objective: To characterize the epidemiology and clinical course of children with juvenile idiopathic arthritis-associated uveitis (JIA-U) in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry and explore differences between African American (AA) and non-Hispanic white (NHW) children.

Methods: There were 4983 children with JIA enrolled in the CARRA Registry. Of those, 3967 NHW and AA children were included in this study.

Meta-analysis confirms association between TNFA-G238A variant and JIA, and between PTPN22-C1858T variant and oligoarticular, RF-polyarticular and RF-positive polyarticular JIA.

Background: Although more than 100 non-HLA variants have been tested for associations with juvenile idiopathic arthritis (JIA) in candidate gene studies, only a few have been replicated. We sought to replicate reported associations of single nucleotide polymorphisms (SNPs) in the PTPN22, TNFA and MIF genes in a well-characterized cohort of children with JIA.

Methods: We genotyped and analyzed 4 SNPs in 3 genes: PTPN22 C1858T (rs2476601), TNFA G-308A, G-238A (rs1800629, rs361525) and MIF G-173C (rs755622) in 647 JIA cases and 751 healthy controls.

Susceptibility to childhood-onset rheumatoid arthritis: investigation of a weighted genetic risk score that integrates cumulative effects of variants at five genetic loci.

Objective: Children with childhood-onset rheumatoid arthritis (RA) include those with rheumatoid factor or anti-citrullinated protein antibody-positive juvenile idiopathic arthritis. To test the hypothesis that adult-onset RA-associated variants are also associated with childhood-onset RA, we investigated RA-associated variants at 5 loci in a cohort of patients with childhood-onset RA. We also assessed the cumulative association of these variants in susceptibility to childhood-onset RA using a weighted genetic risk score (wGRS).

Hierarchy of risk of childhood-onset rheumatoid arthritis conferred by HLA-DRB1 alleles encoding the shared epitope.

Objective: Associations between shared epitope (SE)-encoding HLA-DRB1 alleles and rheumatoid arthritis (RA) are well established. However, only a limited number of studies have investigated these alleles in patients with childhood-onset RA, which is defined as rheumatoid factor- and/or anti-citrullinated protein antibody-positive juvenile idiopathic arthritis. The aims of this study were to investigate the largest cohort of patients with childhood-onset RA for association with SE alleles and to determine whether there is a hierarchy of risk based on the amino acid sequence of the SE.

Development of a vision-related quality of life instrument for children ages 8-18 years for use in juvenile idiopathic arthritis-associated uveitis.

Objective: To determine the validity and reliability of a novel questionnaire to measure vision-related quality of life (VRQOL) in children ages 8-18 years for use in juvenile idiopathic arthritis (JIA)-associated uveitis: the Effects of Youngsters' Eyesight on Quality of Life (EYE-Q).

Methods: Several steps validated the EYE-Q. We interviewed experts and children on how vision affects a child's activities.