National Rheumatology Obstetrics ServicE (ROSE)

Rheumatic musculoskeletal disease (RMD) patients when family planning must consider fertility, disease activity and management from pre-conception to lactation. We have developed, in conjunction with the National Maternity Hospital, Holles St., a dedicated Rheumatology Reproductive service for women with RMD. This service includes a comprehensive multidisciplinary team including a rheumatologist and rheumatology nurse specialist, obstetric and midwifery, maternal medicine, anaesthesia and pharmacy. We identify patients’ emotional and healthcare needs, provide expert advice and aim to achieve maintenance of good disease control and positive reproductive outcomes.   To date, ninety-eight women (mean age (range) = 35 years (19-48)) have been managed. The majority of patients (66%) had inflammatory arthritis and a minority connective tissue disease, vasculitis or other diagnosis. Following analysis of these data and literature review we established an evidence-based care pathway for women with RMD. In conclusion, we describe the first evidence-based reproductive care pathway for women with rheumatic musculoskeletal diseases RMDs in a unique rheumatology reproductive health service, RRHS.

 

The joints of patients with inflammatory arthritis (IA) show a complex microenvironment of neoangiogenesis, immune cell and fibroblast activation leading to inflammation and joint destruction. T cells play a key role in the pathogenesis of both Rheumatoid Arthritis and Psoriatic arthritis, with differential T cell populations associated with both diseases. It has now emerged that T cell subsets can exhibit functional plasticity, particularly, making it difficult to identify discrete T cell subsets on the basis of their cytokine production. Th17 cells appear to be particularly unstable under inflammatory conditions and can become so-called ex-Th17 cells or nonclassical Th1 cells, which start to produce IFN-γ with the eventual loss of IL-17 expression. Interestingly, we have shown enrichment of polyfunctional Th1, Th17 and Ex-Th17 cells in the periphery and synovial fluid of patients with RA and PsA. In addition, the frequency of polyfunctional T cells are associated with disease activity and response to therapy, suggesting they play a key pathogenic role in disease.  Regulatory T cells (Tregs) represent an important peripheral tolerance mechanism that serves to prevent autoimmunity, but fails to constrain inflammation in autoimmune diseases such as RA and PsA. Several studies examining Treg phenotype have reported a decrease in the frequency in peripheral blood of patients with RA/PsA compared with healthy control (HCs), however, studies have also demonstrated enrichment of Tregs at the site of inflammation.  However, they have reduced suppressive function thus allowing pathogenic polyfunctional CD161+ cells to further potentiate inflammation. In this study, we investigated the regulation of effector T cells taken from the RA SF by Tregs. The reduced suppression was in part mediated by the CD161+ Th cells, which exhibited enhanced pathogenicity which were resistant to Treg suppression.

In Rheumatology Reproductive Medicine clinic, RA and PsA patients wishing to achieve pregnancy are assessed when they present with active arthritis and intervention is designed to induce remission before conception. Patients are then followed and closely monitored during pregnancy and post-partum to assess disease activity and possible flare. Studies have shown increased frequency and function of Treg cells that are protective in RA patients who are pregnant, however little is known about polyfunctional T cells.

The present study will investigate effector T cells polyfunctionality and Treg cell function in patients with inflammatory arthritis who are pregnant in (i) remission; (ii) during disease flare, if it occurs; and (iii) post-partum.

 

Biometrics in Inflammatory Arthritis

RA is a complex autoimmune disease resulting from apparently stochastic interactions between genetic and environmental factors. Important environmental factors include smoking, especially heavy smoking, which is the greatest lifestyle risk factor for the development of RA. Environmental factors implicated in addition to smoking include education/social class, breastfeeding, body fat, vitamin D levels, and caffeine and alcohol consumption. According to the WHO, worldwide obesity has nearly tripled since 1975. In parallel with its increase in the general population, obesity has become increasingly common in RA patients.

BMI has been the obesity measure of choice in many previous studies in inflammatory arthritis. However, it has been shown that BMI is not an accurate anthropometric method to diagnose obesity, especially in individuals with altered body compositions (such as inflammatory arthritis patients) due to its inability to discriminate between lean mass and fat mass. Waist circumference has been shown to be superior to BMI in its correlation with visceral fat and has become the preferred measure for abdominal  obesity.Central obesity is defined as having a waist circumference of ≥94 cm in men and ≥80 cm in women The pro-inflammatory nature of fat tissue is now well established. These effects are mediated through the secretion of numerous pro-inflammatory cytokines by adipose tissue, coined adipokines. It is suggested that increased adiposity may have a role in the pathogenesis of inflammatory diseases, however the evidence is conflicting. Numerous studies have demonstrated a positive correlation between BMI and the risk of developing RA. An association between obesity and disease activity in RA has been reported in several previous studies. The Better Anti‐Rheumatic Farmacotherapy observational (BARFOT) study demonstrated that obese patients had higher disease activity and lower rates of remission). Obesity has also been associated with a reduced response to TNF-inhibitors (TNFi).

The aim of this study was to evaluate body composition in seropositive and seronegative rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients and assess associations with disease characteristics and baseline synovial arthroscopic findings. We will also access the effect of Obesity on immune cell responses.

UCD Centre for Arthritis Research (UCD- CAR)

UCD Centre for Arthritis Research (UCD- CAR)

The centre is based at UCD Conway Institute and consists of researchers in UCD and St Vincent’s and Mater University Hospitals. Our interdisciplinary research covers proteomics, computational biology, genetics, stratified medicines, sports and exercise, immunology/mechanisms of disease and animal models of RA.

Our centre has proven highly successful in developing translational experimental approaches including training and performance of mini-arthroscopy and tissue biopsy. The programme based across the UCD Clinical Research Centre, provides whole tissue biopsy explant cultures for research that is an entirely unique resource. Our teams’ ability to perform this research has led to both academic and industry collaborations attracting significant non-exchequer funding from both the EU and the US.

The expertise for this highly developed research programme has led to novel translational research outputs including presentations at the highest quality international research meetings and publication in high impact factor peer-review journals.

Dr Jean Fletcher

In the past decade or so, Th17 cells, have emerged as key players in autoimmune disease, as well as certain cancers and allergies. These potentially dangerous cells are normally regulated by endogenous mechanisms that include Treg cells, which serve to prevent autoimmunity. However in people who develop autoimmune disease, the regulation of Th17 cells goes awry, resulting in inappropriate and damaging inflammation. Dr Fletcher’s research career has focussed on understanding the role and regulation of Th17 cells in human diseases including MS, RA, psoriasis, cancer and hidradenitis suppurativa (HS), which is a debilitating yet under recognised skin disease. Importantly, studying the role of these cells in different diseases allows for greater understanding of common underlying mechanisms that can be translated to benefit for patients. The overarching research aim is to understand the role of Th17 cells in human disease and how they can be targeted to develop new or improved therapies.

Dr Carl Orr

Dr Carl Orr, Consultant Rheumatologist, with a specific interest in understanding molecular disease networks, particularly focusing on Rheumatoid Arthritis in relation to disease stratification, mechanisms and targets, incorporating both clinical and basic science foci. Dr Orr also has an interest in clinical management, and completed an MSc in Leadership and Management Development (Hons) at the Institute of Leadership at RCSI.

Dr Orla Killeen

Dr Orla Killeen graduated from NUIG in 1996. She established the National Centre for Paediatric Rheumatology (NCPR) in 2006, providing care for patients with rheumatic and musculoskeletal disorders both on a local and national level.  Dr Killeen does a joint adolescents transition clinic with prof Eamonn Molloy in SVUH.  She also collaborates with Prof Ursula Fearon/Prof Douglas Veale, on immune cell responses and synovial pathology in children with arthritis associated downs arthropathy. Her area of interest include care of the Young person/Adolescent Rheumatology focusing in particular on Transition as well as juvenile idiopathic arthritis (JIA), Down’s Arthritis, juvenile dermatomyositis (JDM) and Auto-Inflammatory Syndromes.

Phil Gallagher

Phil Gallagher is a Clinical Nurse specialist in Rheumatology SVUH, and is key to the coordination of clinical trials and the establishment of the biologic registries. Phil is critically involved at the interface between the clinical and basic science research teams, in relation to stratification, disease outcomes and  potential new treatment strategies.

Phil also coordinates  RABRI and ASRI, which are the National Rheumatoid Arthritis and AnkSpon registries. In addition, Phil coordinates the National Arthritis Research coalition (ARC).

Dr Aisling Dunne

Our work is focused on assessing inflammatory pathways driven by Osteoarthritis (OA)-associated alarmins or DAMPs (damage-associated molecular patterns). We are currently exploring the signalling events triggered by DAMPs in macrophages and synovial fibroblasts and have identified a number of molecules/pathways activated by OA-associated basic calcium phosphate crystals and S00A8/A9 proteins. We are also conducting a detailed study assessing the impact of traditional and novel orthopaedic implant materials on the host immune system, stem cell differentiation and tissue regeneration.

New Horizons in Rheumatology

New Horizons in Rheumatology took place on Monday 12th & Tuesday 13th November 2018

The programme, which has been established through a number of partnerships with our European & US colleagues & the Centre for Arthritis and Rheumatic Diseases, seeks to deliver an educational forum which provides physicians, trainees and nursing colleagues with the opportunity to experience, review and discuss the key issues in Rheumatic and Musculoskeletal Diseases and novel therapies thereof.

The agenda for this meeting has been developed by an independent steering group of consultants.

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Congratulations to Ms Megan Hanlon for winning best short scientific presentation and to the runners up Dr. Sarah Wade and Dr. Viviana Marzaioli.

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Louise Moore

Candidate Advanced Nurse Practitioner based at The Rheumatic Musculoskeletal Disease Unit, Our Lady’s Hospice and Care Services, Harolds Cross.

Louise, former Clinical Nurse Specialist provides direct care to patients with complex arthritis related problems. She has completed an MSc in Rheumatology Reproductive
Medicine and founded the innovative Maternal Medicine Rheumatology clinic with colleagues at Holles St, National Maternity Hospital.

Gene Browner

Research Assistant based at the Clinical Research Centre.

Gene provides essential support for the arthroscopy research programme and the specialised regional arthritis knee clinic. She provides valuable support to the clinical fellows, research nurses and the patients who attend for arthroscopy, follow-up and clinical assessment.

Edel Meaney

Research Nurse based at the Clinical Research Centre.

Edel has been intrinsic in the development of the arthroscopy research programme over the last 10 years. She provides valuable support to the clinical fellows, research nurses and the patients who attend for arthroscopy, follow-up and clinical assessment.

Hazel Bergin

Research Nurse based at the Clinical Research Centre.

Hazel provides essential support for the arthroscopy research programme and the innovative RA clinical registry. She provides valuable support to the clinical fellows, research nurses and the patients who attend for arthroscopy, follow-up and clinical
assessment.

Dr. Kieran Murray

Kieran Murray graduated from UCD Medical School in 2010. He is a fourth year specialist registrar and has previously worked in Mater Misericordiae University Hospital, Royal Perth Hospital, Beaumont Hospital and University College Hospital Galway. His main research interest is improving outcomes in inflammatory arthritis, through analysing biomarkers, infection risk and management in pregnancy.

Dr. Trudy McGarry

Trudy obtained her BSc in Biomedical Health and Disease from University College Dublin in 2011. In the same year, Trudy was awarded a Molecular Medicine Ireland PhD scholarship for their unique cross-institutional Clinical and Translation Research Scholars Programme (CTRSP). During her PhD, she completed a four month Industry internship with Quintiles Transnational as part of the Global Regulatory Affairs department, providing regulatory ‘Roadmaps’ for large Pharma, advising them on the most efficient strategy to file a new drug application in Europe, South America and Asia. Trudy’s PhD research, entitled ‘Synovial inflammation in Rheumatoid Arthritis is regulated by Toll-like Receptor 2-activated signalling pathways’, was carried out in St. Vincent’s University Hospital and was completed in November 2015. Since this time, she has worked as a Postdoctoral researcher within the Molecular Rheumatology Group and Center for Arthritis and Rheumatic Diseases. At present, Trudy is the UCD Novartis Newman Postdoctoral Fellow and her research focuses on identifying the metabolic and cellular mechanisms that mediate inflammation in the joint. Her work is carried out in close collaboration with Industry partners including Janssen Pharmaceutics and Pfizer. She has received numerous travel grants to present her research within Europe and was awarded best oral presentation at both the MMI and New Horizons in Rheumatology national meetings. Trudy is the current Irish Country Lisiason Officer for EMEUNET (Emerging EULAR Network) and her role is to promote education and collaborative work among young clinicians and researchers in rheumatology and to liaise with other national representatives.

Prof Eamonn Molloy

Prof Eamonn Molloy

Prof Eamonn Molloy is a Founder and Director of The Centre. Prof Molloy is a Consultant Rheumatologist at St. Vincent’s University Hospital and an honorary Professor at University College Dublin. His special interest is in the field of Vasculitis, especially Giant Cell Arteritis and Large Vessel Vasculitis, potentially serious systemic rheumatic diseases that cause inflammation of the circulation. Prof. Molloy provides a state-of-the-art clinical service for these patients, in addition to patients with inflammatory, degenerative and crystal-induced arthritis. He is the principal investigator on a number of active clinical trials and has led a number of translational and interventional innovative studies aimed at delivering novel therapies in these complex conditions

Dr Anne-Barbara Mongey

Dr Anne-Barbara-Mongey is a Member of the Board of The Centre, a Consultant Rheumatologist at St. Vincent’s University Hospital and a Lecturer at University College Dublin. Her special interest is in the field of arthritis connective tissue diseases, including systemic lupus erythematosus, potentially serious systemic rheumatic diseases. Dr. Mongey provides a state-of-the-art clinical service for these patients. In addition, as Lecturer in UCD she is deeply involved in teaching, organising and delivering the medical curriculum.