JIA Subtypes Research Articles

Genetic association of antinuclear antibodies with HLA in JIA patients: a Swedish cohort study

BackgroundJuvenile Idiopathic Arthritis (JIA) is a complex autoimmune disease and the most common chronic rheumatological disease affecting children under the age of 16. The etiology of JIA remains poorly understood, but evidence suggests a significant genetic predisposition.MethodsWe analyzed a Swedish cohort of 329 JIA patients and 728 healthy adult controls using the Illumina OmniExpress array for genotyping. HLA alleles were imputed from GWAS data using the SNP2HLA algorithm.ResultsCase–control analysis yielded 12 SNPs with genome-wide significant association to JIA, all located on chromosome 6 within the MHC class II gene region. Notably, the top SNP (rs28421666) was located adjacent to HLA-DQA1 and HLA-DRB1. HLA-DRB1*08:01, HLA-DQA1*04:01, and HLA-DQB1*04:02 were the haplotypes most strongly associated with an increased risk of JIA in the overall cohort. When analyzing disease specific subtypes, these alleles were associated with oligoarthritis and RF-negative polyarthritis. Within the complex linkage disequilibrium of the HLA-DRB1-DQA1-DQB1 haplotype, our analysis suggests that HLA-DRB1*08 might be the primary allele linked to JIA susceptibility. The HLA-DRB1*11 allele group was also independently associated with JIA and specifically enriched in the oligoarthritis patient group. Additionally, our study revealed a significant correlation between antinuclear antibody (ANA) positivity and specific HLA alleles. The ANA-positive JIA group showed stronger associations with the HLA-DRB1-DQA1-DQB1 haplotype, HLA-DRB1*11, and HLA-DPB1*02, suggesting a potential connection between genetic factors and ANA production in JIA. Furthermore, logistic regression analysis reaffirmed the effects of HLA alleles, female sex, and lower age at onset on ANA positivity.ConclusionsThis study identified distinct genetic associations between HLA alleles and JIA subtypes, particularly in ANA-positive patients. These findings contribute to a better understanding of the genetic basis of JIA and provide insights into the genetic control of autoantibody production in ANA-positive JIA patients. This may inform future classification and personalized treatment approaches for JIA, ultimately improving patient outcomes and management of this disease.

Identifying factors associated with substantially reduced adult height in patients with juvenile idiopathic arthritis: a retrospective cohort study

BackgroundJuvenile idiopathic arthritis (JIA), an autoimmune disease affecting children or adolescents and causing joint or systemic symptoms, reportedly has a negative effect on the patients’ body height. This study aimed to identify factors attributable to substantially reduced adult height (SRAH) in JIA patients.MethodsThis single-center retrospective cohort study included patients from 2009 to 2019 in Taiwan. We collected JIA patients aged > 18 years at enrollment with a definite diagnosis and undergoing regular outpatient clinic follow-up or disease remission. Target height difference (THD), defined by adult height minus mid-parental height, was calculated for each patient. The calculation results yielded two groups, of which positive THD was defined as the optimal height (OH group) and those with THD below two standardized deviations as the SRAH group. Descriptive statistics and logistic regression analysis were used to analyze the data.ResultsOf 92 JIA patients, 57 and 12 were in the OH and the SRAH groups. Earlier disease onset, especially before the six-year-old, was noted in the SRAH group (p = 0.026). The distribution of JIA subtypes differed significantly between the two groups (p < 0.001); enthesis-related arthritis was the commonest subtype in the OH group, and systemic JIA was the commonest in the SRAH group. Half of the patients in the SRAH group had an active disease status at enrollment, which was higher than the OH group (50.0% vs. 21.1%, p = 0.066). More patients in the SRAH group had received orthopedic surgery due to JIA (25% vs. 3.5%, p = 0.034). Multiple logistic regression analysis showed that SRAH was independently related to systemic JIA (OR = 37.6, 95%CI 1.2-1210.5; p = 0.041).ConclusionThe subtype of systemic JIA, with its characteristics of early disease onset and active disease status, was the essential factor that significantly impacted adult height.

P096 Pathway directionality across different immune cell lineages contributes to methotrexate response in juvenile idiopathic arthritis

Abstract Background/Aims Juvenile idiopathic arthritis (JIA) is the most common autoimmune rheumatic disease in children with methotrexate (MTX) as the first line treatment. However, about 50% of JIA patients will not respond well to MTX yet still experience drug side effects. Early prediction to MTX treatment response would be beneficial for patients and families to avoid incurring unnecessary MTX side effects and ongoing uncontrolled inflammation: such validated tools or biomarkers are currently not available. Methods Transcriptional analysis was performed on peripheral blood mononuclear cells (PBMC) from pre-MTX-treated JIA patients (n = 97) of all ILAR JIA subtypes, excluding systemic JIA. RNAseq was performed on total PBMC and sorted immune cell populations: CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD14+ monocytes. Clinical data collected at the time of sampling (baseline) and at the follow-up time (between 3-12 months) were used to define outcomes, measured as change in active joint count (AJC), change in Physician VAS (PhysVAS), and change in cJADAS10. After batch normalisation with ComBat-seq, differential gene expression (DGE) analysis was performed using limma-voom with age, sex, ethnicity, and steroid status included as covariates. Log2 fold changes were utilised to rank genes to implement gene set enrichment analysis (GSEA) by fgsea. Results DGE analysis showed minimal significant differentially expressed (DE) genes that passed 5% false discovery rate (FDR). The greatest number of significant DE genes were observed in CD14+ monocytes, where baseline expression of 13 genes were significantly associated with change in PhysVAS. As alterations of gene expression for a heterogeneous disease such as JIA can be subtle and correlated between genes, GSEA was performed to investigate expression changes at pathway level. Using MSigDb Hallmark pathways, GSEA showed interferon-related and tumor-necrosis-factor pathways as significantly associated with MTX response in all cell types (5% FDR). However, the directionality (up/down regulation) differed between cell lineages, suggesting pathways divergence between T cell and non-T cell lineages. For example, in interferon gamma pathway, up-regulation associated with poor treatment response in T-cells and down-regulation in non-T cells. Preliminary analysis of the leading edge genes of the interferon gamma pathway in the non-T cell lineages showed that many of the genes are driven by interferon alpha, whilst within CD4+ and CD8+ T cells the majority of the leading edge genes are specific to interferon gamma. Conclusion Different directionality of pathways that might be relevant to JIA response to treatment with MTX is observed in different mononuclear cell lineages. This could potentially explain the difficulties of finding biomarkers which correlate with response to treatment from whole blood or PBMC. Shared genes across different interferon-related pathways also suggest that interaction between interferon pathways might be driving the different direction of interferon pathway expression in different cell lineages. Disclosure M. Kartawinata: None. W. Lin: None. B. Jebson: None. K. O'Brien: None. E. Ralph: None. R. Restuadi: None. G.T. Hall: None. S. Castellano: None. C. Wallace: None. L.R. Wedderburn: Grants/research support; LRW Declares in kind contributions to CLUSTER by AbbVie, GSK, UCB, Sobi and Pfizer inc and non renumerated collaborations with Lilly and Novartis.

Screening for juvenile idiopathic arthritis associated uveitis with laser flare photometry in the pediatric rheumatology office: a prospective observational study

BackgroundJuvenile Idiopathic Arthritis (JIA) Associated Uveitis (JIA-U) remains one of the most serious complications of JIA in children. Historically, pediatric JIA is diagnosed by an Optometrist or Ophthalmologist; however, barriers to scheduling increase wait times that may delay diagnosis and treatment. The purpose of this study was to evaluate laser flare photometry (LFP) use to diagnose JIA-U in the Pediatric Rheumatology clinic for patients with JIA.MethodsThis prospective, observational study assessed pediatric patients diagnosed with JIA without a previous history of uveitis between January 2020 and September 2022. All patients underwent at least one evaluation of both eyes using a Kowa FM-600 laser flare photometer during a routine Rheumatology appointment, as well as a standard slit lamp examination (SLE) by optometry or ophthalmology during routine clinical care. Data collected at patient visits included demographics, JIA characteristics, treatment, LFP readings, and anterior chamber (AC) cell grade score utilizing the SUN grading system. Data were summarized using descriptive analyses and the uveitis false positive rate was calculated.ResultsThe study cohort included 58 pediatric patients diagnosed with JIA. The mean age was 8.4 years (1.2–16.3 years) at diagnosis and 11.9 (4.8–16.5 years) at enrollment. The mean duration of disease at time of enrollment was 42 months (range; 0-157 months). Participants were predominantly female (n = 43, 74.1%) and white/Caucasian race (n = 37, 63.8%). The most common JIA subtypes included persistent oligoarticular JIA (n = 19, 32.8%), and RF negative polyarticular JIA (n = 12, 20.7%). There were 12 ANA positive patients (20.7%). At enrollment, 16 patients (27.6%) were not on medications, with 20 (34.5%) on methotrexate, 20 (34.5%) on adalimumab, 6 (10.3%) on tocilizumab, and 5 (8.6%) on etanercept. During the study period, no eye exams detected active uveitis based on SLE with a SUN grade over 0. However, of the 135 LFP readings, 131 (97.0%) were normal, yielding a false positive rate of 3% (95% CI: 0.8%, 7.4%).ConclusionsLFP is a non-invasive tool that can be utilized in the pediatric rheumatology clinic to evaluate for JIA-U. There is a low false positive rate of LFP when compared with standard slit lamp exam.

A clearer vision: insights into juvenile idiopathic arthritis–associated uveitis

The aim of this narrative review is to synthesize existing evidence-based knowledge on juvenile idiopathic arthritis–associated uveitis (JIA-U). We highlight epidemiology, pathophysiology, causes and genetics, risk factors, clinical features, diagnosis and screening, laboratory biomarkers, treatment options, trials with recent advances, and research challenges pertaining to JIA-U. The prevalence of JIA-U varies with different JIA subtypes, most frequently associated with the oligoarticular subtype. The risk factors involved in the development of JIA-U include younger age, antinuclear antibody (ANA) positivity, and the oligoarticular subtype of JIA, along with some specific major histocompatibility complex genes. Certain laboratory biomarkers, such as ANA, rheumatoid factor, interferon-λ, erythrocyte sedimentation rate, and transthyretin, have been used in JIA-U diagnosis, progress monitoring, and prognostication. Clinical features of JIA-U can range from asymptomatic to ophthalmic symptoms like redness, blurred vision, decreased visual acuity, hypopyon, and posterior uveitis, which can lead to retinal detachment and macular edema. The management protocol involves topical and systemic steroids, cycloplegics, disease-modifying antirheumatic drugs, biologic drugs, and surgical options. Early detection combined with prompt treatment is crucial to preventing irreversible vision loss in JIA-U.

Expanded population of low-density neutrophils in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA), a clinically variable disease characterized by autoimmune arthritis, affects children, and its immunopathology remains elusive. Alterations in neutrophil biology play an important role in this disease. In the present study, we aimed to explore the features of low-density neutrophils (LDNs) in patients with JIA. Gene expression of peripheral blood mononuclear cells (PBMCs) from children with distinct subtypes of JIA was analyzed by NanoString Immunology panel. Presence of LDNs was ascertained by flow cytometry and the release of neutrophil-associated products were analyzed by LUMINEX. LDNs were detected in patients' peripheral blood mononuclear cells (PBMCs) after density gradient centrifugation. Transcriptomic analysis of JIA PBMCs revealed that genes related to neutrophil degranulation were markedly upregulated. The number of LDNs and level of their degranulation products increased in patients' PBMCs and correlated with serum calprotectin, but not with disease activity, sedimentation rate and C-reactive protein (CRP) levels. The phenotypes of LDNs varied from those of normal-density neutrophils and healthy donor LDNs. Phenotypical analysis revealed LDNs are immature and primed population with decreased suppressive capacity. A negative correlation between surface proteins CD62L, CD66b, and CD11b and the number of inflamed joints/JADAS was established. Our results describe LDNs as primed, degranulated, immature cells with impaired suppressive activities. This work thus contributes to the increasing body of evidence that LDNs in JIA are altered and their role in the disease immunopathogenesis and possible clinical associations should be investigated further.

E22 Experiences among parents caring for children with juvenile idiopathic arthritis at a tertiary referral hospital in Kenya

Abstract Background Juvenile idiopathic arthritis (JIA) is a highly morbid disease associated with significant rates of preventable permanent damage. The burden and distribution of JIA in African countries vary compared with data across the globe. High-income countries have shown a higher prevalence of JIA compared with low-income countries. Recent studies done in Zambia and Nigeria demonstrated contrasting results in the distributions of the subtypes of JIA within the African continent and those seen in Western countries. Most of these studies were quantitative in nature, looking at health related quality of life within this cohort of patients. Studies done looking at the parental experiences in caring for children for JIA have been reported in high income countries. No studies have been reported within our region to assess the impact of JIA has on parents/guardians caring for children suffering from JIA. Studies from high income countries have shown negative impacts on the social, emotional and financial well-being of guardians caring for children with JIA. We aim to look at impact JIA has on guardians caring for children affected within our context. A few studies in high income countries reported that parental experiences and perceptions play a big role in the long term wellbeing of the child. It still remains unknown the impact JIA might have within our population. Methods This will be a phenomenological type of qualitative study design. 18 potential participants (below 16 years) with a confirmed diagnosis of JIA will be purposively selected from the Kenya pediatric rheumatology registry database (KAPRI). Guardians of patients who meet the inclusion criteria will be scheduled for an introductory meeting on specific days of the week in line with their pediatric rheumatology appointment and in the presence of the primary investigator and the rheumatology consultant. Parental experiences will have been conceptualized using four major indicators: social experience, financial experiences, psychological experience, and medical and treatment-related experiences which impact their overall quality of life. These four concepts have been operationalized using various indicators which were retrieved from literature. The interview guide questionnaire was informed by the conceptual framework which was developed from extensive literature review findings on lived experiences of patients with various health conditions. The concepts in the framework will also serve as the pre-determined themes guiding the deductive thematic data analysis. We shall carry out a deductive thematic data analysis. Hence pre-determined themes extracted from the conceptual framework which was developed from extensive literature review findings on lived experiences of patients will be used in analyzing the data. At the same time, any other new emerging themes will be considered. The transcribed data will be analyzed using the Max for Qualitative Data Analysis (MAXQDA) software program version 2022. Results This project is in its preliminary data collection phase and enrolment of participants is ongoing at the Aga khan University Hospital Nairobi after approval by the Institutional Scientific and Ethical Review Committee (ISERC). Conclusions The results in this study will open avenues for further bigger studies to help promote patient centered care. The results in this study will depict the impact of JIA within our context, as studies done outside of Africa cannot be extrapolated because of the differences in social, economic, and cultural standards and capabilities of practice. Currently, the paucity of data from Africa makes it difficult to predict the burden and impact that JIA pauses on families. This study being a qualitative design, will give an in-depth view on the impact the disease has on the families compared with quantitative studies looking at the quality of life which scarce and despite their values, have limitations such as the inability to include social and cultural aspects and emotional aspects of children's lives and their families and the meaning of life.

Systemic Juvenile Idiopathic Arthritis and Secondary Macrophage Activation Syndrome in Latvia from 2009 to 2020: A Nationwide Retrospective Study.

Background and Objectives: Systemic juvenile idiopathic arthritis (sJIA) is a distinctive JIA subtype with mostly nonspecific systemic clinical features, which can be a diagnostic challenge. This study aimed to analyze our experience with sJIA in Latvia for twelve years: assessing clinical and epidemiological characteristics, the efficacy of therapy, and disease outcomes, including the development of macrophage activation syndrome (MAS). Materials and methods: This is a descriptive study in which we conducted a retrospective case review of all patients with sJIA diagnosis admitted to the only pediatric tertiary centre in Latvia during the period 2009-2020. Results: sJIA was diagnosed in 35 patients with a mean annual incidence rate of 0.85 patients per 100,000 children. Major clinical signs at the first visit were: fever, rash, arthritis, and lymphadenopathy. Almost half of the patients, 48.5%, had a monocyclic disease course, and only 20% of patients had persistent disease. MAS developed in 28.6% of patients. Biological therapy was administered to 48.6% of patients, mostly by tocilizumab, which induced remission in 75% after one year, and in 81.2% after two years without any serious therapy-related complications. In our study, none of the patients had interstitial lung disease, drug reaction with eosinophilia and systemic symptoms (DRESS)-like syndrome, or fatal disease. Conclusions: The incidence and clinical characteristics of sJIA correlate with the literature findings, although MAS was more common than described in other studies. There is a tendency for the persistent disease to decrease with the use of biological therapy. Tocilizumab is an efficient choice of treatment with a good safety profile.

Comparison of the efficacy and safety of methotrexate alone or in combination with leflunomide in the treatment of juvenile idiopathic arthritis: a double-blind, placebo-controlled, randomized trial.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disorder in children. Although methotrexate (MTX) is the first line disease-modifying antirheumatic drug for JIA, many patients do not respond well or cannot tolerate MTX. The aim of this study was to compare the effect of combination therapy of MTX and leflunomide (LFN) with MTX in patients who do not respond to MTX. Eighteen patients (2-20 years old) with polyarticular, oligoarticular or extended oligoarticular subtypes of JIA who did not respond to conventional JIA therapy participated in this double-blind, placebo-controlled, randomized trial. The intervention group received LFN and MTX for 3 months while the control group received oral placebo and MTX at a similar dose to the intervention group. Response to treatment was assessed every 4 weeks using the American College of Rheumatology Pediatric criteria (ACRPed) scale. Clinical criteria, including number of active joints and restricted joints, physician and patient global assessment, Childhood Health Assessment Questionnaire (CHAQ38) score, and serum erythrocyte sedimentation ratelevel, did not differ significantly between groups at baseline and at the end of the 4th and 8th weeks of treatment. Only the CHAQ38 score was significantly higher in the intervention group at the end of the 12th week of treatment. Analysis of the effect of treatment on study parameters revealed that only the global patient assessment score differed significantly between groups (p = 0.003). The results of this study showed that combining LFN with MTX does not improve clinical outcomes of JIA and may increase side effects in patients who do not respond to MTX.

Inflammasome activation and formation of ASC specks in patients with juvenile idiopathic arthritis.

The formation of large intracellular protein aggregates of the inflammasome adaptor ASC is a hallmark of inflammasome activation and characteristic of autoinflammation. Inflammasome activated cells release the highly proinflammatory cytokine IL-1β in addition to ASC specks into the extracellular space. Autoinflammatory activity has been demonstrated in systemic JIA, however minimal data exist on the role of inflammasomes in other JIA subtypes. We therefore investigated, if pyroptotic cells are present in the circulation of oligo- and poly-articular JIA. Peripheral blood of JIA patients (n = 46) was investigated for ASC speck formation, a key step in inflammasome activation, by flow cytometry and immunofluorescence. Free ASC and proinflammatory cytokine levels were determined by ELISA and multiplex assay. Oligo-articular JIA patients showed a significantly increased proportion of ASC speck+ monocytes compared to poly-articular JIA patients. In serum free ASC alone is not sufficient to assess inflammasome activity and does not correlate with ASC speck+ monocytes. Compared to control several cytokines were significantly elevated in samples of JIA patients. JIA serum containing antinuclear antibodies, incubated with ASC specks boosts a secondary inflammation by IL-1β production in macrophages. For the first time, we detect ex vivo inflammasome activation by ASC speck formation in oligo- and poly-articular JIA patients. Most notably, inflammasome activation was significantly higher in oligo- compared to poly-articular JIA patients. This data suggests that inflammasome derived autoinflammation may have a greater influence in the previously thought autoimmune oligo-articular JIA patients.

Patients' and parents' satisfaction to improve patient care in JIA: factors determining acceptable symptom state measured with JAMAR.

The aim of this study was to identify factors associated with patients' and parents' reported satisfaction with JIA care, measured with the juvenile arthritis child and parent acceptable symptom state (JA-CASS and JA-PASS, respectively). A prospective cohort of 239 JIA patients and 238 parents in a tertiary centre who completed the juvenile arthritis multidimensional assessment report (JAMAR) was analysed cross-sectionally. The primary outcomes were positive JA-CASS and JA-PASS, respectively. Items in the JAMAR, as well as JIA subtype, demographics, and disease activity parameters, were analysed in univariate analysis. A multivariable logistic regression analysis was used to build models explaining the variance of the primary outcome as a dependent variable. According to the JAMAR, 141 (59.0%) of 239 patients and 149 (62.6%) of 238 parents were satisfied with their or their child's current condition. For patients, the determinants in the final model were a shorter duration of morning stiffness (P = 0.001), a lower age at disease onset (P = 0.044), a longer disease duration (P = 0.009) and a higher rating of the patient's well-being measured on a visual analogue scale (VAS) (P = 0.004). For parents, the determinants were the current state of disease activity (current state of persistent activity P = 0.002, relapse P < 0.005), problems at school (P = 0.002) and the items regarding quality of life (QoL) (P = 0.005). Our data highlight the importance of patients' and parents' opinions in the evaluation of disease activity, and support their integration into the shared decision-making in daily clinical practice to improve the quality of medical care.

P57 What are the outcomes of persistent oligoarthritis? A systematic review plan

Introduction/BackgroundOligoarthritis, a sub-type of JIA, can be categorised as persistent or extended. Children with persistent oligoarthritis, involving <5 joints, are often excluded from clinical trials as it is considered a milder form of JIA and managed less aggressively. Therefore, less is known about the longer term outcomes of those with persistent oligoarthritis. This knowledge could lead to better targeting of existing therapies for individuals and higher quality patient information.Description/MethodThis aim of this research is to conduct a systematic literature review on the clinical and patient-reported outcomes of persistent oligoarthritis. This abstract presents plans and current status of the review.Inclusion criteria for this systematic review are 1) inception cohorts with at least partial prospective data collection, 2) available in English language, 3) includes at least 50 patients with persistent oligoarthritis using ILAR criteria, 4) investigates clinical or patient-reported outcome. Exclusion criteria are 1) not specifically presenting or analysing outcomes in persistent oligoarthritis and 2) not reporting disease duration or follow-up time points from diagnosis at the point of outcome measurements.Search terms related to ‘oligoarthritis’, (variants of juvenile oligoarthritis plus outcomes of interest) were used in MEDLINE and Embase from 01/01/1997 to 30/05/2022 to cover the advent of current ILAR categories to present. These terms were also entered into PubMed from 30/05/2020 to 30/05/2022 to include publications published online ahead of print.Quality assessment, including common biases, of selected articles will be assessed using relevant questions from the Pasma et al. quality assessment (QA) tool.Primary outcomes are the core JIA outcome variables (active joint counts, limited joint count, physician’s global assessment, parent global evaluation, erythrocyte sedimentation rate and additional functional status (CHAQ/HAQ). Additional outcomes are 1) remission status, 2) uveitis status, 3) pain, 4) Health-related Quality of Life and 5) treatment response.One reviewer will initially screen titles and abstracts. Two reviewers will then screen the full text of selected articles independently and agree the master list. The first reviewer will then extract data regarding study populations and outcome and another reviewer will check a selection of the extracted data. If there is disagreement or uncertainty between the two reviewers at any stage, a third reviewer will adjudicate.Discussion/ResultsTo date 1051 publications have been highlighted for initial review (title and abstract) by the first reviewer. The second review is now underway by the two reviewers and preliminary results will be ready to present soon. The review has been registered with Prospero (ID: CRD42022291943).Key learning points/ConclusionThere is an unmet need for improved understanding of outcome in persistent oligoarthritis. This systematic review will help inform treatment targets and future research in this common ILAR JIA category.

Pharmacological treatment patterns in patients with juvenile idiopathic arthritis in the Netherlands: a real-world data analysis.

To investigate medication prescription patterns among children with JIA, including duration, sequence and reasons for medication discontinuation. This study is a single-centre, retrospective analysis of prospective data from the electronic medical records of JIA patients receiving systemic therapy aged 0-18 years between 1 April 2011 and 31 March 2019. Patient characteristics (age, gender, JIA subtype) and medication prescriptions were extracted and analysed using descriptive statistics, Sankey diagrams and Kaplan-Meier survival methods. Over a median of 4.2 years follow-up, the 20 different medicines analysed were prescribed as monotherapy (n = 15) or combination therapy (n = 48 unique combinations) among 236 patients. In non-systemic JIA, synthetic DMARDs were prescribed to almost all patients (99.5%), and always included MTX. In contrast, 43.9% of non-systemic JIA patients received a biologic DMARD (mostly adalimumab or etanercept), ranging from 30.9% for oligoarticular persistent ANA-positive JIA, to 90.9% for polyarticular RF-positive JIA. Among systemic JIA, 91.7% received a biologic DMARD (always including anakinra). When analysing medication prescriptions according to their class, 32.6% involved combination therapy. In 56.8% of patients, subsequent treatment lines were initiated after unsuccessful first-line treatment, resulting in 68 unique sequences. Remission was the most common reason for DMARD discontinuation (44.7%), followed by adverse events (28.9%) and ineffectiveness (22.1%). This paper reveals the complexity of pharmacological treatment in JIA, as indicated by: the variety of mono- and combination therapies prescribed, substantial variation in medication prescriptions between subtypes, most patients receiving two or more treatment lines, and the large number of unique treatment sequences.

P155 Implementing change in treatment delivery for children and young people during a pandemic

Abstract Background/Aims The Paediatric Rheumatology Team at the Great North Children’s Hospital (GNCH) provides care to children and young people (CYP) across the northern region. On average 70 new CYP are diagnosed annually with rheumatic conditions. Approximately 1/3 will require long-term treatments and long-term rheumatology follow-up. The team support over 300 patients receiving treatments for at home, with 75 CYP requiring regular treatments administered in hospital. Tocilizumab targets IL-6 and is used to treat rheumatic conditions. Tocilizumab, approved for use in children with certain subtypes of JIA in 2011, is normally administered via an intravenous infusion on the Paediatric Day Unit, at GNCH. The procedure takes approximately 3 hours and involves a cannula for administration. Part of Continuity and Emergency Planning for the COVID- 19 pandemic the Medicines &amp; Healthcare Products Regulatory Agency (MHRA) compiled a list in April 2020 of medications including tocilizumab, not to be exported from the UK or hoarded. Tocilizumab was a proposed treatment for hyper-inflammatory response for COVID-19 and concern that supplies would be affected. NHS hospitals were advised to reduce routine activity and footfall through the hospital. The team agreed the need to consider alternative treatment delivery. Methods A patient cohort were identified attending GNCH for intravenous infusions. 38/65 (58%) patients were receiving tocilizumab. The pharmacist agreed to switch CYP from intravenous to subcutaneous tocilizumab. A total of 34 eligible patients were identified (32/38 current patients and two new patients) Using a multi-disciplinary approach, the pharmacist established agreement, arranged supply and delivery of medication to the families. The CNS contacted all families via nurse-led telephone clinic and invited eligible CYP to a face-to-face clinic, to received counselling and training to administer. The rheumatology consultants supported the change with prescription management. Over a 6-week period all eligible CYP transferred to subcutaneous form of tocilizumab administered at home. Medication was transported to families via home care delivery company. Results 34 patients switched, 9/34(26%) reported localised injection-site reactions, varying in severity but could lead to discontinuation of treatment. An inconsistent approach to managing these reactions was recognised by the pharmacist and CNS. Collaboration with the paediatric allergy teams, devised a standardised approach to manage injection-site reactions using an algorithm. Conclusion • Reduce pressure on precious hospital resources • More convenient for families - minimise long distance travel for treatment and time off school/ work • True collaboration and recognition of multidisciplinary team working swiftly to find a solution to a problem impacting upon patients, their family and the Trust • Algorithm devised by the paediatric pharmacist using easily accessible oral and topical treatments for families to use at home to manage site reactions. • Tocilizumab has proven to be useful in treatment of critically unwell patients infected with COVID-19. Disclosure R. Wyllie: None.

Association between interleukin-10 polymorphisms and juvenile idiopathic arthritis: a meta-analysis.

The aim of this review is to investigate IL-10 polymorphisms (-1082 G/A, -819 C/T, and -592 C/A) and their association with susceptibility to JIA. A meta-analysis was conducted after database search for relevant articles (MEDLINE and EMBASE). A total of seven studies involving 1495 patients and 1670 controls were considered in the meta-analysis. There was no association between the IL-10 -1082 G/A, -819 C/T, and -592 C/A polymorphisms and JIA in allele contrast and any of the genetic models (allele contrast: odds ratio [OR] 0.90, 95% confidence interval [CI] 0.79-1.02, P=0.09; OR=0.97, 95% CI 0.83-1.13, P=0.68; OR=0.92, 95% CI 0.81-1.06, P=0.24, respectively). In subgroup analysis, none of the subtypes of JIA including systemic, rheumatoid factor (RF)-positive polyarticular, RF-negative polyarticular, and oligoarticular was not significantly associated with IL-10 polymorphism. Meta-analysis of the IL-10 haplotype revealed no association between GCC, ACC, and ATA haplotypes and JIA. This meta-analysis showed that IL-10 polymorphisms were not associated with risk of JIA.

Single-cell analysis reveals heterogeneity of juvenile idiopathic arthritis fibroblast-like synoviocytes with implications for disease subtype

BackgroundFibroblast-like synoviocytes (FLS) play a crucial role in JIA pathogenesis; however, the mechanisms by which they contribute to disease progression are not well described. Previous studies demonstrated that rheumatoid arthritis FLS are heterogeneous, and subpopulations with transformed, aggressive phenotypes cause invasive and destructive disease activity. We employ single-cell RNA-sequencing (scRNA-seq) to investigate JIA FLS heterogeneity and gene expression that distinguishes JIA subtypes.MethodsJIA FLS cell lines from three persistent oligoarticular, three pre-extension oligoarticular, and three polyarticular subtypes were cultured. scRNA-seq was performed by Genewiz according to 10 × Genomics Chromium protocols. SeuratR package was used for QC, analysis, and exploration of data.ResultsFLS are heterogeneous and have characteristics of fibroblasts, chondrocytes, and smooth muscle cells. The chondrocyte-like subpopulation is the predominant cell type and percentages of this subpopulation increase with disease severity. Despite overlapping subpopulations, the chondrocyte-like cells have unique genetic fingerprints that distinguish between JIA subtypes. LRRC15, GREM1, and GREM2 are overexpressed in chondrocyte-like cells from persistent oligoarticular JIA FLS compared to pre-extension oligoarticular JIA FLS. S100A4, TIMP3, and NBL1 are overexpressed in pre-extension oligoarticular JIA FLS compared to polyarticular JIA FLS. CRLF1, MFAP5, and TNXB are overexpressed in persistent oligoarticular JIA FLS compared to polyarticular JIA FLS.ConclusionsWe found biologically relevant differences in gene expression between JIA subtypes that support a critical role for FLS in pathogenesis. We also demonstrate that gene expression within the chondrocyte-like subpopulation can be used to distinguish between these subtypes.

Frequência de uveíte em pacientes pediátricos com artrite idiopática juvenil em hospital terciário

OBJECTIVE: Observe the profile and the frequency of juvenile idiopathic arthritis-associated uveitis (JIA-U) in patients followed at a tertiary pediatric hospital. METHODS: Retrospective study of patients with JIA attended from January to July 2019 at the pediatric rheumatology department. RESULTS: 41 charts were reviewed, from which four (9.75%) presented uveitis, all of them being diagnosed with JIA before seven years old and all of them with ocular complications. Concerning the subtype of JIA, two patients had persistent oligoarticular subtype and two had the negative rheumatoid factor poliarticular subtype. Three patients (75%) with JIA-U were antinuclear-antibody (ANA) positive. All patients presented uveitis within the first 4 years of JIA. CONCLUSION: Around 10% of the patients with JIA presented uveitis. In the JIA-U group, the following were observed: ANA positivity, JIA diagnosis before 7 years old and development of uveitis within the first 4 years of articular disease. The presence of ocular complications in all of the patients with JIA-U reveals the severity and the importance of tracking back this ocular manifestation.

EXPRESSION OF TOLL-LIKE RECEPTORS 4 ON CD14 + MONOCYTES IN JUVENILE IDIOPATHIC ARTHRITIS.

The aim: The work is aimed at determining the relationship between TLR4 expression on CD14+monocytes in whole heparinized blood and B1a lymphocyte synthesis in various subtypes of JIA. Materials and methods: 64children aged3to17years were examined, including42children with different subtypes of JIA and22healthy children. The intensity of TLR4 expression onCD14+monocytes was determined in whole heparinized blood incubated with a CD14-FITC/TLR4-PE monoclonal antibody cocktail(Biolegend, USA)using flow cytometry. Monoclonal antibodies (BD Bioscience) were used to determine the main subpopulations of lymphocytes. Results: A statistically significant increase in TLR4 expression has been determined in JIA compared to the control group. The most prominent TLR4 expression was detected in children with oligoarthritis, while in systemic arthritis, there was no statistical difference compared to healthy children. High TLR4 expression on peripheral CD14+monocytes inversely depends on the activity of the autoimmune process, which may have a protective effect against the aseptic inflammation.Increased TLR4 expression involves a statis¬tically significant increase in the percentage and quantity of В1а lymphocytes(p≤0.05). Conclusions: A statistically significant increase in TLR4 expression on CD14+monocytes in whole heparinized blood was detected in patients with JIA compared to healthy children. Children with oligoarthritis had the highest rates, which indicates possible differences in the development of pathogenetic processes in different subtypes of arthritis. Determining the degree of TLR4 activation on CD14+monocytes is reasonable for predicting JIA activity.

P015 Imaging findings in cervical spine in patients with Juvenile Idiopathic Arthritis in Tunisia

Abstract Background Juvenile Idiopathic Arthritis (JIA) is a chronic disease characterized by prolonged synovial inflammation that may cause structural joint damage. However, little is known about cervical spine involvement in JIA. The main objective of this study is to describe radiological findings of the cervical spine in patients with JIA. Methods We conduct a retrospective monocentric study. All JIA patients were included (ILAR criteria). Sociodemographic, JIA subtype, and clinical characteristics were collected. Disease activity at JIA diagnosis was evaluated by JADAS10 (Juvenile Arthritis Disease Activity Score) in poly and oligoarticular subtypes and by BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) in arthritis-related enthesitis form. Cervical spine radiographs including anteroposterior and lateral with flexion views were analyzed. A p-value &amp;lt; 0.05 was considered significant. Results We included 25 patients (16 girls and 9 boys) diagnosed with JIA with a mean age at disease onset of 9.9 ± 3.9 [3–16]. The median disease duration was 36 months (IQR 25–75%; 30–84). The JIA subtypes were in decreasing order of frequency: Enthesitis-related Arthritis (n = 9), Oligoarticular (n = 6), Polyarticular RF- (n = 4), Polyarticular RF + (n = 2), Systemic (n = 2), Psoriatic Arthritis (n = 1), and Undifferentiated (n = 1). Median ESR and CRP were 17 mm/h [2–98] and 15.4 mg/l [0–56] respectively. The Median BASDAI score was 2.8 [1–6.3]. Median JADAS10 score was 5.3 [0–20]. Four patients (16%) were on long-term corticosteroid therapy. Five patients (20 %) have a cervical spine involvement with the following subtypes: Polyarticular (n = 2), enthesitisenthesitis-related arthritis (n = 2), and systemic (n = 1). Clinical manifestations were neck pain (n = 3) and limited range of motion (n = 4). Neurological examination noted brisk deep tendon reflexes (n = 6), positive Babinski reflex (n = 1) and positive Hoffmann reflex (n = 2). No patient had a neurological deficit. The conventional radiographs of the cervical spine showed: loss of cervical lordosis (n = 2), diastasis C1-C2 (n = 3), erosion of the odontoid process (n = 1), and anterior ankylosis (n = 3). Subsequent cervical spine MRI confirmed these findings and showed pannus at the craniocervical junction in one case and block vertebra of C6-C7 in another case. Atlanto-axial subluxation was anteroposterior in 3 patients and rotatory in one. Conclusion Cervical spine involvement is frequent and underestimated in JIA, and its radiological features are various. Hence, regular radiographic monitoring of the cervical spine is required to prevent the development of this complication.

P036 Juvenile Idiopathic Arthritis in adulthood: outcomes of oligo and polyarticular forms?

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease of childhood that can cause major physical disability, impairing patients' ability to lead a normal adult life. The objective of this study was to assess the outcomes of oligo- and polyarticular JIA in adulthood as well as the progression to authentic rheumatoid arthritis (RA). Methods We conducted a retrospective study including adult patients with JIA (diagnosed according to the International League of Associations for Rheumatology [ILAR]). Data collected included age, gender, disease characteristics (JIA subtype, disease duration). The progression to an authentic RA was determined by checking the response to the ACR/EULAR 2010 classification criteria. Results Twenty-eight patients were included in this study. There was a female predominance with a sex ratio of 1.5. The mean age of disease onset was 6 years and 2 months [2–17]. The mean age at inclusion was 29.5 years [18–64]. The frequency of each JIA subtype was as follows: polyarticular with RF + (n = 14), polyarticular with RF- (n = 9), oligoarthritis (n = 5). The polyarticular forms: RF+ and RF- evolved into genuine seropositive and seronegative RA in 71.4% and 66.7% of cases, respectively. Among the oligoarticular JIA subtype, an extension of the disease to a seronegative RA was noted in one patient (20%). Hip involvement was noted in 20% of patients. Carpal tunnel syndrome and elbow arthritis were found in 28.5% and 14.3% of patients, respectively. Regarding treatment modalities and at the time of recruitment, 36.3% of RAs were treated with Methotrexate, and 33% were on biological treatment. Ten percent of the patients dropped out of school because of disease flares and deformities. Conclusion Our study showed oligo- and polyarticular JIA evolves in most of the cases towards an authentic RA causing deformities and handicaps. Earlier management is necessary to allow a better transition to adulthood.