Household food security and dietary diversity in south-eastern Nigeria.

The aim of this study was to investigate household food security (access) level and the dietary diversity of households in the Nsukka Local Government Area in South-eastern Nigeria. From 20 local communities of Nsukka, 390 women were randomly sampled from the women's group and asked to complete a survey that determined the Household Food Insecurity Access Scale scores and the Household Dietary Diversity Scores (HDDS). The descriptive results indicated a high level of food insecurity with 82.6% households reporting various degrees of food insecurity. Over half of the sampled population experienced insufficient food quality. They either ate unwanted food (65.9%), limited variety (63.1%), or unpreferred food (64.6%). Some households experienced insufficient food intake by going a whole day without food (38.2%), go to sleep hungry (45.1%), or have no food of any kind (49%). The analysis of variance showed no significant difference (p = 0.428) in the food security level of households headed by males as compared with those headed by females. Approximately 53.6% of households fell at or below the average HDDS; males headed 48% of these households, while females headed 64%. The chi-square test indicated factors associated with household food security including age, education, work status and income, whereas the gender of the household head, household size and marital status were not significantly associated. Public-private partnerships, nutrition orientation and food intervention programs could improve food security in this area.

The suboptimal fibrinolytic response in COVID-19 is dictated by high PAI-1.

BACKGROUND: Severe COVID-19 disease is associated with thrombotic complications and extensive fibrin deposition. This study investigates whether the hemostatic complications in COVID-19 disease arise due to dysregulation of the fibrinolytic system. METHODS: This prospective study analyzed fibrinolytic profiles of 113 patients hospitalized with COVID-19 disease with 24 patients with non-COVID-19 respiratory infection and healthy controls. Antigens were quantified by Ella system or ELISA, clot lysis by turbidimetric assay, and plasminogen activator inhibitor-1 (PAI-1)/plasmin activity using chromogenic substrates. Clot structure was visualized by confocal microscopy. RESULTS: PAI-1 and its cofactor, vitronectin, are significantly elevated in patients with COVID-19 disease compared with those with non-COVID-19 respiratory infection and healthy control groups. Thrombin activatable fibrinolysis inhibitor and tissue plasminogen activator were elevated in patients with COVID-19 disease relative to healthy controls. PAI-1 and tissue plasminogen activator (tPA) were associated with more severe COVID-19 disease severity. Clots formed from COVID-19 plasma demonstrate an altered fibrin network, with attenuated fiber length and increased branching. Functional studies reveal that plasmin generation and clot lysis were markedly attenuated in COVID-19 disease, while PAI-1 activity was elevated. Clot lysis time significantly correlated with PAI-1 levels. Stratification of COVID-19 samples according to PAI-1 levels reveals significantly faster lysis when using the PAI-1 resistant (tPA) variant, tenecteplase, over alteplase lysis. CONCLUSION: This study shows that the suboptimal fibrinolytic response in COVID-19 disease is directly attributable to elevated levels of PAI-1, which attenuate plasmin generation. These data highlight the important prognostic potential of PAI-1 and the possibility of using pre-existing drugs, such as tenecteplase, to treat COVID-19 disease and potentially other respiratory diseases.

A Novel Algorithm Using Within-leg Calibration for Enhanced Accuracy of Detection of Arthritis by Infrared Thermal Imaging in Children.

OBJECTIVE: To standardize and improve the accuracy of detection of arthritis by thermal imaging. METHODS: Children with clinically active arthritis in the knee or ankle, as well as healthy controls, were enrolled to the development cohort; another group of children with knee symptoms was enrolled to the validation cohort. Ultrasound was performed in the arthritis subgroup for the development cohort. Joint exam by certified rheumatologists was used as a reference for the validation cohort. Infrared thermal data were analyzed using custom software. Temperature after within-limb calibration (TAWiC) was defined as the temperature differences between joint and ipsilateral mid-tibia. TAWiC of knees and ankles was evaluated using ANOVA across subgroups. Optimal thresholds were determined by receiver-operating characteristic analysis using Youden index. RESULTS: There were significant differences in mean and 95th TAWiC of knee in anterior, medial, lateral views, and of ankles in anterior view, between inflamed and uninflamed counterparts (P < 0.05). The area under the curve was higher by 30% when using TAWiCknee than that when using absolute temperature. Within the validation cohort, the sensitivity of accurate detection of arthritis in the knees using both mean and 95th TAWiC from individual views or all 3 views combined ranged from 0.60 to 0.70, and the specificity was > 0.90 in all views. CONCLUSION: Children with active arthritis or tenosynovitis in knees or ankles exhibited higher TAWiC than healthy joints. Our validation cohort study showed promise for the clinical utility of infrared thermal imaging for arthritis detection.

The feasibility of developing biomarkers from peripheral blood mononuclear cell RNAseq data in children with juvenile idiopathic arthritis using machine learning approaches.

BACKGROUND: The response to treatment for juvenile idiopathic arthritis (JIA) can be staged using clinical features. However, objective laboratory biomarkers of remission are still lacking. In this study, we used machine learning to predict JIA activity from transcriptomes from peripheral blood mononuclear cells (PBMCs). We included samples from children with Native American ancestry to determine whether the model maintained validity in an ethnically heterogeneous population. METHODS: Our dataset consisted of 50 samples, 23 from children in remission and 27 from children with an active disease on therapy. Nine of these samples were from children with mixed European/Native American ancestry. We used 4 different machine learning methods to create predictive models in 2 populations: the whole dataset and then the samples from children with exclusively European ancestry. RESULTS: In both populations, models were able to predict JIA status well, with training accuracies > 74% and testing accuracies > 78%. Performance was better in the whole dataset model. We note a high degree of overlap between genes identified in both populations. Using ingenuity pathway analysis, genes from the whole dataset associated with cell-to-cell signaling and interactions, cell morphology, organismal injury and abnormalities, and protein synthesis. CONCLUSIONS: This study demonstrates it is feasible to use machine learning in conjunction with RNA sequencing of PBMCs to predict JIA stage. Thus, developing objective biomarkers from easy to obtain clinical samples remains an achievable goal.

The Evolution and Cultural Framing of Food Safety Management Systems-Where From and Where Next?

The aim of this paper is to review the development of food safety management systems (FSMS) from their origins in the 1950s to the present. The food safety challenges in modern food supply systems are explored and it is argued that there is a need for a more holistic thinking approach to food safety management. The narrative review highlights that while the transactional elements of how FSMS are developed, validated, implemented, monitored, and verified remains largely unchanged, how organizational culture frames the operation and efficacy of FSMS is becoming more important. The evolution of a wider academic and industry understanding of both the influence of food safety culture (FS-culture) and also how such culture frames and enables, or conversely restricts the efficacy of the FSMS is crucial for consumer well-being. Potential research gaps worthy of further study are identified as well as recommendations given for the application of the research findings within the food industry.

Toward New Classification Criteria for Juvenile Idiopathic Arthritis: First Steps, Pediatric Rheumatology International Trials Organization International Consensus.

OBJECTIVE: To revise the current juvenile idiopathic arthritis (JIA) International League of Associations for Rheumatology (ILAR) classification criteria with an evidence-based approach, using clinical and routine laboratory measures available worldwide, to identify homogeneous clinical groups and to distinguish those forms of chronic arthritis typically seen only in children from the childhood counterpart of adult diseases. METHODS: The overall project consists of 4 steps. This work represents Step 1, a Delphi Web-based consensus and Step 2, an international nominal group technique (NGT) consensus conference for the new provisional Pediatric Rheumatology International Trials Organization JIA classification criteria. A future large data collection of at least 1000 new-onset JIA patients (Step 3) followed by analysis and NGT consensus (Step 4) will provide data for the evidence-based validation of the JIA classification criteria. RESULTS: In Step 1, three Delphi rounds of interactions were implemented to revise the 7 ILAR JIA categories. In Step 2, forty-seven questions with electronic voting were implemented to derive the new proposed criteria. Four disorders were proposed: (a) systemic JIA; (b) rheumatoid factor-positive JIA; (c) enthesitis/spondylitis-related JIA; and (d) early-onset antinuclear antibody-positive JIA. The other forms were gathered under the term "others." These will be analyzed during the prospective data collection using a list of descriptors to see whether the clustering of some of them could identify homogeneous entities. CONCLUSION: An international consensus was reached to identify different proposed homogeneous chronic disorders that fall under the historical term JIA. These preliminary criteria will be formally validated with a dedicated project.

A Pilot Study of Infrared Thermal Imaging to Detect Active Bone Lesions in Children With Chronic Nonbacterial Osteomyelitis.

OBJECTIVE: Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease. An inexpensive and rapid imaging tool, infrared thermal imaging, was evaluated for its utility to detect active bone lesions in extremities of children with CNO. METHODS: Children with suspected active CNO and healthy controls were enrolled. All subjects underwent infrared thermal imaging of the lower extremities. Patients in the CNO group also received a magnetic resonance imaging (MRI) examination. Hyperintensity within bone marrow on a fluid-sensitive T2-weighted MRI sequence was considered confirmatory for inflammation. Infrared thermal data were analyzed using custom software by dividing the leg below the knee into 3 equal segments longitudinally and adding the distal femur segment as an equal length above the knee. Median and 95th percentile temperatures were recorded for each leg segment. Temperature differences between inflamed and uninflamed segments in all subjects (both intersubject and intrasubject) were evaluated using a linear mixed-effects model. RESULTS: Thirty children in the suspected/known CNO group and 31 healthy children were enrolled. In the healthy control group, males had significantly higher temperature in their lower extremities than females (P < 0.05). There was no difference in temperature detected between inflamed leg segments of patients with CNO versus uninflamed leg segments of the healthy control group. However, within the CNO group, significantly higher temperatures were detected for inflamed versus uninflamed distal tibia/fibula segments (P < 0.01). CONCLUSION: Children with active CNO lesions in the distal tibia/fibula exhibited higher regional temperatures on average than healthy extremities. Larger studies are warranted to further evaluate the clinical utility of infrared thermal imaging for CNO detection.

Flares of Disease in Children with Clinically Inactive Juvenile Idiopathic Arthritis Were Not Correlated with Ultrasound Findings.

OBJECTIVE: The validity of our current definitions for clinically inactive disease (CID) in juvenile idiopathic arthritis (JIA) based on physical examination is challenged by the development of advanced musculoskeletal imaging tools. We aimed to prospectively determine the prevalence of abnormal ultrasound (US) findings in children with CID in JIA and their clinical significance. METHODS: Children aged ≥ 4 years with CID and a history of arthritis from a single tertiary center were approached over 1 year. Standard US of knees, tibiotalar joints, subtalar joints, and wrists were performed at baseline and at a followup visit. US images were scored by 2 pediatric musculoskeletal radiologists. RESULTS: Forty children with CID were enrolled and followed clinically. The median duration of inactive disease was 1 year. The most common International League of Associations for Rheumatology JIA categories were extended oligoarticular JIA (30%) and rheumatoid factor-negative polyarthritis (38%). At baseline, among a total of 289 joints scanned, 24 joints (8%) had at least 1 abnormal finding in 18 (45%) of 40 subjects. When evaluated at the individual joint level against flares identified during followup exams, these baseline US findings had a sensitivity of 15% and a positive predictive value of 12%. The predictive performance of the second US was even less. CONCLUSION: Our study demonstrates that nearly half of children with CID had abnormal US findings in 1 of 8 commonly affected joints. These findings did not correlate with subsequent clinical flares in up to 2 years of followup.

Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus.

Resistance to infection is critically dependent on the ability of pattern recognition receptors to recognize microbial invasion and induce protective immune responses. One such family of receptors are the C-type lectins, which are central to antifungal immunity. These receptors activate key effector mechanisms upon recognition of conserved fungal cell-wall carbohydrates. However, several other immunologically active fungal ligands have been described; these include melanin, for which the mechanism of recognition is hitherto undefined. Here we identify a C-type lectin receptor, melanin-sensing C-type lectin receptor (MelLec), that has an essential role in antifungal immunity through recognition of the naphthalene-diol unit of 1,8-dihydroxynaphthalene (DHN)-melanin. MelLec recognizes melanin in conidial spores of Aspergillus fumigatus as well as in other DHN-melanized fungi. MelLec is ubiquitously expressed by CD31+ endothelial cells in mice, and is also expressed by a sub-population of these cells that co-express epithelial cell adhesion molecule and are detected only in the lung and the liver. In mouse models, MelLec was required for protection against disseminated infection with A. fumigatus. In humans, MelLec is also expressed by myeloid cells, and we identified a single nucleotide polymorphism of this receptor that negatively affected myeloid inflammatory responses and significantly increased the susceptibility of stem-cell transplant recipients to disseminated Aspergillus infections. MelLec therefore recognizes an immunologically active component commonly found on fungi and has an essential role in protective antifungal immunity in both mice and humans.

Brief Report: The Genetic Profile of Rheumatoid Factor-Positive Polyarticular Juvenile Idiopathic Arthritis Resembles That of Adult Rheumatoid Arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) comprises 7 heterogeneous categories of chronic childhood arthritides. Approximately 5% of children with JIA have rheumatoid factor (RF)-positive arthritis, which phenotypically resembles adult rheumatoid arthritis (RA). Our objective was to compare and contrast the genetics of RF-positive polyarticular JIA with those of RA and selected other JIA categories, to more fully understand the pathophysiologic relationships of inflammatory arthropathies. METHODS: Patients with RF-positive polyarticular JIA (n = 340) and controls (n = 14,412) were genotyped using the Immunochip array. Single-nucleotide polymorphisms were tested for association using a logistic regression model adjusting for admixture proportions. We calculated weighted genetic risk scores (wGRS) of reported RA and JIA risk loci, and we compared the ability of these wGRS to predict RF-positive polyarticular JIA. RESULTS: As expected, the HLA region was strongly associated with RF-positive polyarticular JIA (P = 5.51 × 10-31 ). Nineteen of 44 RA risk loci and 6 of 27 oligoarticular/RF-negative polyarticular JIA risk loci were associated with RF-positive polyarticular JIA (P < 0.05). The RA wGRS predicted RF-positive polyarticular JIA (area under the curve [AUC] 0.71) better than did the oligoarticular/RF-negative polyarticular JIA wGRS (AUC 0.59). The genetic profile of patients with RF-positive polyarticular JIA was more similar to that of RA patients with age at onset 16-29 years than to that of RA patients with age at onset ≥70 years. CONCLUSION: RF-positive polyarticular JIA is genetically more similar to adult RA than to the most common JIA categories and thus appears to be a childhood-onset presentation of autoantibody-positive RA. These findings suggest common disease mechanisms, which could lead to novel therapeutic targets and shared treatment strategies.

The Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans: Toward Comparative Effectiveness in the Pediatric Rheumatic Diseases.

The pediatric rheumatic diseases are a heterogeneous group of rare diseases, posing a number of challenges for the use of traditional clinical and translational research methods. Innovative comparative effectiveness approaches are needed to efficiently study treatment strategies and disease outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed the consensus treatment plan (CTP) approach as a comparative effectiveness tool for research in pediatric rheumatology. CTPs are treatment strategies, developed by consensus methods among CARRA members, intended to reduce variation in treatment approaches, standardize outcome measurements, and allow for comparison of the effectiveness of different approaches with the goal of improving disease outcomes. To date, CTPs have been published for 8 different diseases and disease manifestations. The approach has been successfully piloted for juvenile localized scleroderma, systemic juvenile idiopathic arthritis (JIA), polyarticular JIA, dermatomyositis, and lupus nephritis. Large-scale studies are underway for systemic JIA and polyarticular JIA, with the CARRA patient registry serving as the data collection platform. These studies have been designed with stakeholder involvement, including active input from CARRA providers, patients, and parents, with the goal of increasing feasibility and ensuring the relevance of the outcomes. These studies include ancillary biologic specimen collection intended to support additional translational and mechanistic studies. Data from these ongoing CTP studies will provide more information on the ability of this approach to identify effective treatment strategies and improve outcomes in the pediatric rheumatic diseases.

Triangulation and the importance of establishing valid methods for food safety culture evaluation.

The research evaluates maturity of food safety culture in five multi-national food companies using method triangulation, specifically self-assessment scale, performance documents, and semi-structured interviews. Weaknesses associated with each individual method are known but there are few studies in food safety where a method triangulation approach is used for both data collection and data analysis. Significantly, this research shows that individual results taken in isolation can lead to wrong conclusions, resulting in potentially failing tactics and wasted investments. However, by applying method triangulation and reviewing results from a range of culture measurement tools it is possible to better direct investments and interventions. The findings add to the food safety culture paradigm beyond a single evaluation of food safety culture using generic culture surveys.

Genome-Wide Association Meta-Analysis Reveals Novel Juvenile Idiopathic Arthritis Susceptibility Loci.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease and has a strong genomic component. To date, JIA genetic association studies have had limited sample sizes, used heterogeneous patient populations, or included only candidate regions. The aim of this study was to identify new associations between JIA patients with oligoarticular disease and those with IgM rheumatoid factor (RF)-negative polyarticular disease, which are clinically similar and the most prevalent JIA disease subtypes. METHODS: Three cohorts comprising 2,751 patients with oligoarticular or RF-negative polyarticular JIA were genotyped using the Affymetrix Genome-Wide SNP Array 6.0 or the Illumina HumanCoreExome-12+ Array. Overall, 15,886 local and out-of-study controls, typed on these platforms or the Illumina HumanOmni2.5, were used for association analyses. High-quality single-nucleotide polymorphisms (SNPs) were used for imputation to 1000 Genomes prior to SNP association analysis. RESULTS: Meta-analysis showed evidence of association (P < 1 × 10-6 ) at 9 regions: PRR9_LOR (P = 5.12 × 10-8 ), ILDR1_CD86 (P = 6.73 × 10-8 ), WDFY4 (P = 1.79 × 10-7 ), PTH1R (P = 1.87 × 10-7 ), RNF215 (P = 3.09 × 10-7 ), AHI1_LINC00271 (P = 3.48 × 10-7 ), JAK1 (P = 4.18 × 10-7 ), LINC00951 (P = 5.80 × 10-7 ), and HBP1 (P = 7.29 × 10-7 ). Of these, PRR9_LOR, ILDR1_CD86, RNF215, LINC00951, and HBP1 were shown, for the first time, to be autoimmune disease susceptibility loci. Furthermore, associated SNPs included cis expression quantitative trait loci for WDFY4, CCDC12, MTP18, SF3A1, AHI1, COG5, HBP1, and GPR22. CONCLUSION: This study provides evidence of both unique JIA risk loci and risk loci overlapping between JIA and other autoimmune diseases. These newly associated SNPs are shown to influence gene expression, and their bounding regions tie into molecular pathways of immunologic relevance. Thus, they likely represent regions that contribute to the pathology of oligoarticular JIA and RF-negative polyarticular JIA.

Sleep Disturbances and Neurobehavioral Performance in Juvenile Idiopathic Arthritis.

OBJECTIVE: To examine the extent of polysomnographic (PSG) sleep disturbances [obstructive apnea hypopnea index (OAHI), number of wake bouts, arousals, periodic limb movements] and the effect of OAHI on neurobehavioral performance in juvenile idiopathic arthritis (JIA) with obstructive sleep apnea (OSA), JIA without OSA, and controls without OSA, adjusting for intelligence quotient (IQ), pain, medications, daytime sleepiness, and wake bouts. METHODS: Children 6-11 years, 68 with JIA and 67 controls, underwent 1 night of PSG and completed self-reported daytime sleepiness surveys, multiple sleep latency tests for physiological sleepiness, and neurobehavioral performance tests the next day. RESULTS: Compared with JIA and controls without OSA, mean OAHI and arousals were significantly higher in JIA with OSA (p < 0.001, respectively). In comparison with JIA and controls without OSA, mean simple reaction time and sustained attention were significantly slower in JIA with OSA, adjusting for IQ, pain, any medication, daytime sleepiness, and wake bouts. CONCLUSION: Elevated OAHI is suggestive of obstructive sleep apnea and a comorbidity in JIA that may predispose children with JIA to daytime sleepiness and impaired neurobehavioral performance.

TCR repertoire sequencing identifies synovial Treg cell clonotypes in the bloodstream during active inflammation in human arthritis.

OBJECTIVES: The imbalance between effector and regulatory T (Treg) cells is crucial in the pathogenesis of autoimmune arthritis. Immune responses are often investigated in the blood because of its accessibility, but circulating lymphocytes are not representative of those found in inflamed tissues. This disconnect hinders our understanding of the mechanisms underlying disease. Our goal was to identify Treg cells implicated in autoimmunity at the inflamed joints, and also readily detectable in the blood upon recirculation. METHODS: We compared Treg cells of patients with juvenile idiopathic arthritis responding or not to therapy by using: (i) T cell receptor (TCR) sequencing, to identify clonotypes shared between blood and synovial fluid; (ii) FOXP3 Treg cell-specific demethylated region DNA methylation assays, to investigate their stability and (iii) flow cytometry and suppression assays to probe their tolerogenic functions. RESULTS: We found a subset of synovial Treg cells that recirculated into the bloodstream of patients with juvenile idiopathic and adult rheumatoid arthritis. These inflammation-associated (ia)Treg cells, but not other blood Treg cells, expanded during active disease and proliferated in response to their cognate antigens. Despite the typical inflammatory-skewed balance of immune mechanisms in arthritis, iaTreg cells were stably committed to the regulatory lineage and fully suppressive. A fraction of iaTreg clonotypes were in common with pathogenic effector T cells. CONCLUSIONS: Using an innovative antigen-agnostic approach, we uncovered a population of bona fide synovial Treg cells readily accessible from the blood and selectively expanding during active disease, paving the way to non-invasive diagnostics and better understanding of the pathogenesis of autoimmunity.

Congruence between polysomnography obstructive sleep apnea and the pediatric sleep questionnaire: fatigue and health-related quality of life in juvenile idiopathic arthritis.

PURPOSE: To examine the congruence between polysomnography obstructive apnea hypopnea index (OAHI) and parent-reported obstructive sleep apnea (OSA) symptoms in 6- to 11-year-old children with juvenile idiopathic arthritis (JIA) and controls; and to compare fatigue and quality of life in JIA and control children based on OAHI and OSA symptoms. METHODS: Sixty-eight children with JIA and 75 controls and a parent participated. Children underwent one night of polysomnography in a sleep laboratory. Parents completed the sleep-related breathing disorders scale-pediatric sleep questionnaire (PSQ), and both children and parents completed the Pediatric Quality of Life Generic Core Scale and the Multidimensional Fatigue Scale. RESULTS: In JIA, 86% who met the OAHI clinical criteria for OSA (≥1.5) were above the PSQ OSA symptom cut-off score with a sensitivity of 0.86 and a specificity of 0.28. In the control group, 63% who met the OAHI clinical criteria for OSA were above the PSQ OSA symptom cut-off score, with a sensitivity of 0.63 and a specificity of 0.42. All children above both the clinical criteria for OAHI and OSA symptom cut-off score had the most impaired quality of life and greater fatigue compared to those below both the clinical criteria for OAHI and the OSA symptom cut-off score. CONCLUSION: Children who meet clinical criteria for OSA and also scored high on a parent-reported screening tool for OSA symptoms had the most impaired quality of life and more fatigue. The PSQ has potential to identify children at risk for OSA.

Limits of Peripheral Blood Mononuclear Cells for Gene Expression-Based Biomarkers in Juvenile Idiopathic Arthritis.

Juvenile Idiopathic Arthritis (JIA) is one of the most common chronic disease conditions affecting children in the USA. As with many rheumatic diseases, there is growing interest in using genomic technologies to develop biomarkers for either diagnosis or to guide treatment ("personalized medicine"). Here, we explore the use of gene expression patterns in peripheral blood mononuclear cells (PBMC) as a first step approach to developing such biomarkers. Although PBMC carry many theoretical advantages for translational research, we have found that sample heterogeneity makes RNASeq on PBMC unsuitable as a first-step method for screening biomarker candidates in JIA. RNASeq studies of homogeneous cell populations are more likely to be useful and informative.

Whole blood expression profiling from the TREAT trial: insights for the pathogenesis of polyarticular juvenile idiopathic arthritis.

BACKGROUND: The Trial of Early Aggressive Therapy in Juvenile Idiopathic Arthritis (TREAT trial) was accompanied by a once-in-a-generation sample collection for translational research. In this paper, we report the results of whole blood gene expression analyses and genomic data-mining designed to cast light on the immunopathogenesis of polyarticular juvenile idiopathic arthritis (JIA). METHODS: TREAT samples and samples from an independent cohort were analyzed on Affymetrix microarrays and compared to healthy controls. Data from the independent cohort were used to validate the TREAT data. Pathways analysis was used to characterize gene expression profiles. Furthermore, we correlated differential gene expression with new information about functional regulatory elements within the genome to develop models of aberrant gene expression in JIA. RESULTS: There was a strong concordance in gene expression between TREAT samples and the independent cohort. In addition, rheumatoid factor (RF)-positive and RF-negative patients showed only small differences on whole blood expression profiles. Analysis of the combined samples showed 158 genes represented by 176 probes that showed differential expression between TREAT subjects at baseline and healthy controls. None of the differentially expressed genes were encoded within linkage disequilibrium blocks containing single nucleotide polymorphisms known to be associated with risk for JIA. Functional analysis of these genes showed functional associations with multiple processes associated with innate and adaptive immunity, and appeared to reflect overall suppression of STAT1-3/interferon response factor-mediated pathways. CONCLUSIONS: Despite their limitations, whole blood expression profiles clearly distinguish children with polyarticular JIA from healthy controls. Whole blood expression profiles identify several immunologic pathways of biologic relevance that will need to be pursued in homogeneous cell populations in order to clarify mechanisms of pathogenesis. TRIAL REGISTRATION: ClinicalTrials.gov registry #NCT00443430 , originally registered 2 March 2007 and last updated 30 May 2013.