Madeleine Rooney

Queen's University Belfast | QUB · Centre for Infection and Immunity

Background Corticosteroids (CS) are widely used for rapid-action or induction treatment in children and young people (CYP) with juvenile idiopathic arthritis (JIA). Given a lack of evidence base on CS induction regimen for CYP with JIA, and since criteria for choosing CS are based on healthcare professional (HCP) preference, further research is nee...

Introduction: Current delivery routes and doses of corticosteroid (CS) treatment in juvenile idiopathic arthritis (JIA) are principally based on clinician and patient preference, rather than scientific evidence. A clinical trial is needed in the future to ascertain the most effective routes and doses of CS in JIA. Objectives: To explore families’ e...

Introduction: Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of adherence to MTX is important...

Viral infections elicit anti-viral antibodies and have been associated with various chronic diseases. Detection of these antibodies can facilitate diagnosis, treatment of infection and understanding of the mechanisms of virus associated diseases. In this work, we assayed anti-viral antibodies using a novel high density-nucleic acid programmable pro...

Objectives: The aims of this study were to investigate the extent of MRI-determined joint disease (erosion and synovitis) in SLE and to link this to autoantibody profiles known to be relevant to SLE, including ACPA, RF and anti-RA33 antibodies. Methods: Contrast-enhanced MRI of the hand and wrist was performed in 34 symptomatic SLE patients and...

Development and validation of a selective and sensitive LCMS method for the determination of methotrexate polyglutamates in dried blood spots (DBS). DBS samples [spiked or patient samples] were prepared by applying blood to Guthrie cards which was then dried at room temperature. The method utilised 6-mm disks punched from the DBS samples (equivalen...

Background Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic, childhood onset, autoimmune diseases with variable clinical outcomes. Objectives We investigated whether profiling of the synovial fluid (SF) proteome by a fluorescent dye based, two-dimensional gel (DIGE) approach could distinguish the subset of patients...

Objectives To evaluate the relationship between Computed Radiography (CR) Pixel values and disease activity scores obtained for the knees of newly diagnosed Juvenile Idiopathic Arthritis (JIA) children. Methods Children with newly diagnosed untreated JIA were recruited. Both knees were scored for disease activity on a score of 0-3. Weight-bearing a...

Background The limited application of Ultrasound(US) and MRI to date in SLE is revealing a higher percentage of erosive disease than previous estimates1. Such erosive arthropathy in lupus when associated with rheumatoid factor (RF) or anti-CCP antibody (ACPA) is often referred to as ‘rhupus’ to indicate a mixture of the character of rheumatoid dise...

Background Juvenile idiopathic arthritis (JIA) is the one of the most common chronic childhood diseases with a prevalence of around 1/1000 [1]. Over time JIA can result in persistent joint inflammation leading to chronic pain and stiffness, joint deformity and damage. Disease aetiology remains unknown. Investigation of disease pathology at the leve...

Background Juvenile Idiopathic Arthritis (JIA) is the main cause of chronic arthritis in children, and it can lead to joint damage and disability. Detecting early articular involvement in JIA is therefore of crucial importance to prevent cartilage and bone damage in these young patients. Since 2004 we have undertaken a prospective study of children...

Background The role of specific cytokines in lupus arthritis has not been elucidated1. This is in stark contrast to rheumatoid arthritis (RA) where an abundance of research has culminated in an advancing era of novel biologic drugs. Objectives To analyse the cytokine profile in SLE patients with erosive, non-erosive arthritis and arthralgia as clas...

Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood with a prevalence of around 1 in 1000. Without appropriate treatment it can have devastating consequences including permanent disability from joint destruction and growth deformities. Disease aetiology remains unknown. Investigation of disease pathology at t...

Supplementary materials.

Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic autoimmune diseases with variable clinical outcomes. We investigated whether the synovial fluid (SF) proteome could distinguish a subset of patients in whom disease extends to affect a large number of joints. SF samples from 57 patients were obtained around time of i...

Objective: To examine the evidence of an association between hypermobility and musculoskeletal pain in children. Methods: A systematic review of the literature was performed using the databases PubMed, EMBASE, NHS Evidence, and Medline. Inclusion criteria were observational studies investigating hypermobility and musculoskeletal pain in children...

Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of autoantibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients. A pilot study...

Table S1, a complete list of NAPPA proteins, presenting the Entrez gene symbol, protein name, cellular location and molecule type for each protein produced on the NAPPA array within the current study; Table S2, functional networks of NAPPA proteins, listing the physiological and pathological functions of 25 networks constructed from the constituent...

Figure S1, transcriptional regulation of antigen clusters, showing magnified sections of the hierarchical cluster analysis heatmap in Figure 3Ato illustrate two distinct clusters of 49 proteins targeted by antibodies within the plasma of study subjects. The proteins responsible for transcriptional regulation of the target antigens within cluster 1...

This review examines the biomarker development process by using rheumatic disorders as the disease model for discussion. We evaluate the current role of biomarkers in the practice of rheumatology and discuss their likely role in the future. We define the essential components of the biomarker development pipeline and discuss the issue of fitness for...

Despite the anticipated boom stemming from proteomic investigations, the rate at whichnovel protein biomarkers are introduced into clinical practice has remained static over thepast 20 years. The reality is that approaches to both discover and validate proteinbiomarkers remain inadequate, and consequently, many areas of medicine, including thebroad...

Juvenile idiopathic arthritis (JIA) consists of a heterogeneous group of inflammatory disorders, within which there are a number of clinical subgroups. Diagnosis and assignment to a particular subgroup can be problematical and more concise methods of subgroup classification are required. This study of the synovial membrane characterises the immunoh...

To develop a provisional definition for the evaluation of response to therapy in juvenile dermatomyositis (DM) based on the Paediatric Rheumatology International Trials Organisation juvenile DM core set of variables. Thirty-seven experienced pediatric rheumatologists from 27 countries achieved consensus on 128 difficult patient profiles as clinical...

To prospectively compare clinical examination of the ankle structures with ultrasound (US) findings. In 42 children with juvenile idiopathic arthritis (JIA; 25 girls, 17 boys, mean age 11.3 yrs, range 2.3-22.3 yrs), a total of 61 swollen/painful ankles were assessed clinically and ultrasonographically. Accurate clinical examination of the entire an...

Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic, childhood onset, autoimmune diseases with variable clinical outcomes. We investigated whether profiling of the synovial fluid (SF) proteome by a fluorescent dye based, two-dimensional gel (DIGE) approach could distinguish patients in whom inflammation extends to aff...

Current clinical, laboratory or radiological parameters cannot accurately diagnose or predict disease outcomes in a range of autoimmune disorders. Biomarkers which can diagnose at an earlier time point, predict outcome or help guide therapeutic strategies in autoimmune diseases could improve clinical management of this broad group of debilitating d...

The C allele of a single nucleotide polymorphism (SNP), rs6897932, located in the interleukin-7 receptor alpha chain (IL7RA) was recently found to be associated with multiple sclerosis and Type I diabetes. We analysed 13 SNPs in the IL7RA gene in a combined cohort of patients with chronic inflammatory arthropathies (rheumatoid arthritis and juvenil...

Juvenile idiopathic arthritis reflects a group of clinically heterogeneous arthritides hallmarked by elevated concentrations of circulating immune complexes. In this study, the circulating immune complex proteome was examined to elucidate disease-associated proteins that are overexpressed in patients with an aggressive, and at times destructive, di...

The ankle joint is frequently involved in juvenile idiopathic arthritis (JIA), but it is unclear whether this is predominantly due to synovitis, tenosynovitis, or both. We performed clinic-based ultrasound examination to assess the prevalence of synovitis and tenosynovitis in children with JIA felt clinically to have active inflammatory disease of...

Synovial fluid is a potential source of novel biomarkers for many arthritic disorders involving joint inflammation, including juvenile idiopathic arthritis. We first compared the distinctive protein 'fingerprints' of local inflammation in synovial fluid with systemic profiles within matched plasma samples. The synovial fluid proteome at the time of...

To review outcome measures and treatment costs in children with juvenile idiopathic arthritis (JIA) and low bone mineral density (BMD) and/or fragility fractures. To review evidence for effectiveness and safety of bisphosphonates and calcium and/or vitamin D in these children. To assess long-term bone health in adults with JIA. Major databases were...

The -168A-G polymorphism has been shown to influence transcription of the MHC2TA gene and has been implicated in several inflammatory/autoimmune disorders. Attempts to reproduce these findings have been inconclusive. We investigated the role of this promoter single nucleotide polymorphism (SNP) in 440 multiple sclerosis (MS), 293 rheumatoid arthrit...

This review aims to summarise our knowledge to date on the protein complement of the synovial fluid (SF). The tissues, structure and pathophysiology of the synovial joint are briefly described. The salient features of the SF proteome, how it is composed and the influence of arthritic disease are highlighted and discussed. The concentrations of prot...

Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with polygenic autoimmune background. We analysed the IL-4 +33 C/T and IL-4R Q551R single nucleotide polymorphisms (SNPs) in 294 RA, 72 JIA and 165 controls from Northern Ireland. Analysis of the individual phenotypes (RA or JIA) showed that both the IL-4...

The synovial fluid proteome in juvenile idiopathic arthritis was investigated to isolate joint-specific biomarkers that are expressed in patients displaying recurrent joint inflammation. To identify the synovial specific proteome, matched synovial fluid and plasma samples were subjected to protein separation by 2-dimension electrophoresis (2DE). Fo...

Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with an autoimmune background. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) protein plays a key role in the down-regulation of T cell activation. We analyzed the CTLA4 +49A/G and CT60 polymorphisms in cohorts of Northern Irish RA and JIA patients and heal...

Despite the increasing use of musculoskeletal ultrasound (MSUS) as a clinical tool in rheumatology, there is no consensus yet regarding the standards required to achieve a basic level of competence in the use of this imaging technique. A number of sonographers worldwide are developing curricula and standardizing teaching methods in order to improve...

The Disease Activity Score1 is widely used to quantify disease activity and gauge response to treatment. A rather complex calculation conceals the relative contribution of each measure to the composite score. The 28 joint version (DAS28) is used in the British Society for Rheumatology guidelines to determine response to anti-tumour necrosis factor...

Studies examining the relation between bone mineral density (BMD) and fruit and vegetable consumption during adolescence are rare. Our objective was to determine whether usual fruit and vegetable intakes reported by adolescents have any influence on BMD. BMD was measured by dual-energy X-ray absorptiometry at the nondominant forearm and dominant he...

In an observational study of 1335 boys and girls aged 12 and 15 years, higher intakes of carbonated soft drinks (CSDs) were significantly associated with lower bone mineral density at the heel, but only in girls. Owing to the upward trend in CSD intake in adolescence, this finding may be of concern. High consumption of carbonated soft drinks (CSD)...

To determine whether polymorphisms in the interferon-gamma (IFNgamma)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA). Four microsatellite markers, located in a 118-kb interval that contains both the IFNgamma and IL-26 genes on chromosome 12q15, were typed in 251...

To identify possible imbalance of tumour necrosis factor alpha (TNFalpha) and its soluble receptors in the different subgroups of juvenile chronic arthritis (JCA). Serum and synovial fluid samples from 45 children were examined, 25 pauciarticular JCA, 13 polyarticular JCA and seven spondyloarthropathy. TNFalpha, sTNFRI and sTNFRII levels were measu...

To determine whether growth hormone (rhGH) affects bone mineral metabolism and bone mineral content (BMC, g/cm) in a therapeutic trial of recombinant growth hormone in growth retarded children with juvenile chronic arthritis (JCA) treated with steroid. BMC was measured in 20 children (of whom 17 were treated with corticosteroid) before and after on...

In this Grand Round, two children are described with atypical generalized scleroderma and severe failure to thrive. Neither had Raynaud's phenomenon nor evidence of gastrointestinal (GI) disease. Treatment with non-steroidal anti-inflammatory drugs, prednisone, D-penicillamine, alpha and gamma interferon was unsuccessful in reversing the scleroderm...

The aim of this study was to compare clinical evaluation of the site of hindfoot synovitis with contrast-enhanced magnetic resonance imaging (MRI) findings in children with juvenile chronic arthritis (JCA), and to evaluate the efficacy of selective guided intra-articular steroid injections. Thirteen symptomatic ankles of 11 consecutive JCA patients...

We report two boys with juvenile dermatomyositis (JDM) complicated by pancreatitis. One also had hepatitis and probably mild bowel vasculitis, while the other had catastrophic bowel vasculitis with multiple perforations. Both were on corticosteroids, but had features of active vasculitis. The former improved with high-dose i.v. pulsed methylprednis...

The purpose of this study was to assess the value of contrast-enhancement in MR diagnosis of hip joint disease in patients with juvenile chronic arthritis. Fourteen hips in seven children (four girls, three boys; mean age, 11 years; range, 7-17 years) with juvenile chronic arthritis for a mean duration of seven years (range, 3-15 years) were imaged...

The inflammatory cytokines interleukin 1 beta (IL-1 beta) interleukin 6 (IL-6), tumour necrosis factor alpha (TNF alpha) and the anti-inflammatory peptide--the interleukin 1 (IL-1) receptor antagonist--were measured in the plasma of children with juvenile chronic arthritis (JCA). In the two subgroups studied (polyarticular JCA and systemic JCA), th...

To evaluate the effect of recombinant human growth hormone (rhGH) on the linear growth of children with persistently active juvenile chronic arthritis (JCA), most of whom were receiving steroid therapy. All of them were severely growth retarded, but had adequate GH secretion. After monitoring height velocity for one year, children were treated for...

Immunohistological features which might predict the clinical course and outcome of rheumatoid arthritis were sought by examining multiple synovial membrane samples obtained by needle biopsy from the knee joints of 57 patients who had not received disease modifying antirheumatic drugs. Clinical measurements, but not biopsies, were repeated one year...

Interleukin 1 beta (IL-1 beta) is a polypeptide with pro-inflammatory and immunopotentiating effects in vivo and in vitro. With relevance to rheumatoid arthritis (RA) IL-1 augments release of prostanoids, proteinases and oxygen metabolites and is a potent inducer of bone and cartilage resorption. Although high levels of IL-1 have been found in rheu...

This chapter is concerned with the investigation of drug-induced changes in immune function. Before discussing specific investigative techniques, a few general points should be made. Many tests for evaluation of the immune system are complex, time-consuming and expensive. The tests chosen should, therefore, be informative, discriminating and, most...

The spectrum of immunohistological change in the affected joints of patients with rheumatoid arthritis has been well described. In this study, the immunohistological features in synovial membrane obtained from apparently uninvolved knee joints of 16 patients with active untreated rheumatoid arthritis were examined and compared to tissue from contro...

The immunohistologic characteristics of synovial membrane obtained from patients with active rheumatoid arthritis (RA) were correlated with disease activity and spontaneous in vitro synthesis of IgM rheumatoid factor (RF) by peripheral blood mononuclear cells (MNC). Positive correlations were found between the intensity of inflammatory cell infiltr...

Multiple samples of synovial membrane were obtained by needle biopsy from 24 patients with rheumatoid arthritis (RA) before, and 1 year after, standard antirheumatic drug therapy was given. Changes in the immunohistologic features of the synovial membrane (read blindly) were compared with the clinical course of RA in each patient. A composite clini...

One hundred forty-five synovial biopsy specimens were obtained from 30 procedures performed on the knee joints of 29 patients with rheumatoid arthritis. All patients had clinically active rheumatoid arthritis and none had received slow-acting disease-modifying drugs or intraarticular corticosteroids. Scores were assigned to each biopsy specimen for...

Five (8.5 per cent) of 59 adult patients with cystic fibrosis described a characteristic arthropathy which was episodic, self-limiting and polyarticular, affecting large and small peripheral joints without evidence of progression to joint damage. The five patients with arthropathy did not differ from the remaining 54 with respect to manifestations...