Day :
- Rheumatology | Orthopedic Biomechanics Research| Lupus | Physiotherapy | Soft Tissue Rheumatism | Sports Medicine | Autoimmunity | Orthopedic Trauma | Musculoskeletal Disorders
Location: Husaria
Chair
Nikolaos Christodoulou
Athens Medical Group, Greece
Co-Chair
Małgorzata Wisłowska
Central Clinical Hospital MSWiA Warsaw, Poland
Session Introduction
Hala Lotfy Fayed
Kasr Al Ainy School of Medicine - Cairo University, Egypt
Title: Frequency of vitamin D inadequacy among Saudi males visiting a rheumatology outpatient clinic of a tertiary hospital in Al Qassim region: Effect of vitamin D supplementation
Biography:
Hala Lotfy Fayed is a Lecturer of Rheumatology and Rehabilitation, Kasr Al Ainy School of Medicine, Cairo University and has her expertise in research related issues to autoimmune rheumatic diseases, as well as metabolic bone diseases. She works at Kasr Al Ainy School of Medicine which is a research and teaching hospital, affiliated with the Faculty of Medicine. She has passion in improving health and wellbeing. Her open and contextual work aims for improving healthcare. She has built this model after years of experience in research, evaluation, teaching and administration both in hospital and education institutions.
Abstract:
Statement of the Problem: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease; characterized by an immune response against post translationally modified proteins in particular citrullinated proteins. Recent studies have found that ACPA response matures shortly before clinical disease manifests itself. Data suggested the association of an increased risk of ACPA positivity with IUD use prompting the need to investigate this association suggesting a possible etiopathogenic role of IUD use in Egyptian female RA patients. We hypothesized that the IUD might be a potent environmental trigger through its potential to induce chronic subtle renewed tissue injury and chronic inflammation triggering citrullination at the site of the endometrium thus aggravating and perpetuating RA disease in female RA patients.
Objective: To study the impact/effect of commonly used contraceptive methods on rheumatoid arthritis (RA) disease activity, severity, and damage in a cohort of Egyptian female RA patients.
Methods: Two hundred female RA patients were enrolled and divided into two groups; non-contraception users (50 patients) and contraception users (150 patients). The latter group was further subdivided according to the method of contraceptive method used into: 89 intrauterine device (IUD)-users; 45 combined oral contraceptives (COC)-users; 16 injectable users. All patients underwent thorough history taking with special emphasis on contraception history, clinical examination, and assessment by routine laboratory tests, rheumatoid factor (RF) and antibodies to citrullinated protein antigens (ACPA). Rheumatoid arthritis disease activity was assessed using Disease Activity Score 28 using CRP (DAS28/ CRP), while RA disease severity was assessed using Rheumatoid Arthritis Severity Scale (RASS). Bilateral hand x-rays were done and interpreted by the Short Erosion Scale (SES).
Results: The percentage of ACPA seropositivity among IUD-users was 75.3%; the highest among all studied subgroups. IUD-users showed significantly higher ACPA titers (p=0.020), as well as longer disease duration (p=0.021) compared to other methods-users. The RASS was significantly higher in injectable users in comparison to other methods-users followed by the IUD-users (p=0.008). COC-users had the least RASS. However, there were no significant differences regarding DAS28/CRP or SES between different contraceptive methods-users. There was positive correlation between ACPA titers and RASS.
Conclusion: The increased ACPA positivity as well as higher ACPA titers in women who are currently IUD-users suggests a possible etiopathogenic role for IUD in onset and perpetuation of RA disease. Mechanisms by which IUD could increase RA-related autoimmunity risk were discussed. Whether cessation of IUD use in RA patients might improve their current state of disease need further study.
Maria Maslinska
National Institute of Geriatrics, Rheumatology and Rehabilitation, Poland
Title: Does early primary Sjogren’s syndrome really exist?
Biography:
Maria Maślińska is the Deputy Head of the Early Arthritis Clinic of the National Institute of Geriatrics, Rheumatology and Rehabilitation in Warsaw. She is the Deputy Editor-in-Chief of Reumatologia Journal. Her research projects are unclassified arthritis and spondyloarthropathies. She received the Third Degree Group Award of the Rector of the Medical University of Warsaw for the scientific achievements in the field of the research related to the patho mechanism of inflammation. She is a member of the Polish Society for Rheumatology and of the Polish Union of the Physician-Writers. She is an author and co-author of scientific publications: articles and book chapters. She is a Lecturer of numerous courses, seminars and conferences for general practitioners and rheumatologists.
Abstract:
Introduction & Aim: The study assessed differences in symptoms and immunological parameters between younger (<45) and older primary Sjogren’s syndrome (pSS) patients.
Patients: Group I (GI): n=50 patients with pSS ≥ 45 years old, women [F] (86.7%) and men [M] (10.3%); Group II (GII) n=25 < 45 years old, 24 [F] and 1 [M].
Methods: WBC, CRP, RF, ESR, Serum concentration of gamma globulins and of C4, C3 complement components were assessed. Antinuclear antibodies (ANA) titers, serum anti-SS-A, anti-SS-B and cytokine (BAFF, APRIL, FLT-3L, TNF-β, IL-21) levels were determined. The histopathological evaluation (focus score) and immunohistochemistry (presence of CD3+, CD4+, CD19+, CD21+ CD35+ cells) of minor salivary gland biopsies were studied. A Schirmer’s test and ocular staining (lissamine green and fluorescein) eye assessments were carried out.
Findings: In GII leukopenia, higher gamma globulins and C3 complement component concentrations were observed. In GI Schirmer's test results were significantly lower. In GII higher LT-α levels were observed (p=0.049). No other differences in cytokine serum concentrations were observed. There were no differences in FS evaluation between groups, but in GII the number of dendritic cells (CD35+, CD21+) assessed with immunohistochemistry was significantly higher P=0.042 and P=0.031 respectively.
Conclusion & Significance: GI presented greater immune activity with less severe dryness symptoms. GII showed higher levels of lymphotoxin α (P=0.049) indicating Th1 lymphocytes activity and the active immune response in peripheral lymphoid organs. The presence of CD 35+ and CD 21+ cells in salivary glands in GII may indicate the active early disease phase and dendritic cells activity. Younger pSS patients may present no evident symptoms of dryness, inspite of the dynamic autoimmune process development (confirmed in lab tests).
Hala Lotfy Fayed
Kasr Al Ainy School of Medicine - Cairo University, Egypt
Title: Rheumatoid arthritis activity and severity in relation to commonly used contraceptive methods in a cohort of Egyptian female patients
Biography:
Hala Lotfy Fayed is a Lecturer of Rheumatology and Rehabilitation, Kasr Al Ainy School of Medicine, Cairo University and has her expertise in research related issues to autoimmune rheumatic diseases, as well as metabolic bone diseases. She works at Kasr Al Ainy School of Medicine which is a research and teaching hospital, affiliated with the Faculty of Medicine. She has passion in improving health and wellbeing. Her open and contextual work aims for improving healthcare. She has built this model after years of experience in research, evaluation, teaching and administration both in hospital and education institutions.
Abstract:
Statement of the Problem: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease; characterized by an immune response against post translationally modified proteins in particular citrullinated proteins. Recent studies have found that ACPA response matures shortly before clinical disease manifests itself. Data suggested the association of an increased risk of ACPA positivity with IUD use prompting the need to investigate this association suggesting a possible etiopathogenic role of IUD use in Egyptian female RA patients. We hypothesized that the IUD might be a potent environmental trigger through its potential to induce chronic subtle renewed tissue injury and chronic inflammation triggering citrullination at the site of the endometrium thus aggravating and perpetuating RA disease in female RA patients.
Objective: To study the impact/effect of commonly used contraceptive methods on rheumatoid arthritis (RA) disease activity, severity, and damage in a cohort of Egyptian female RA patients.
Methods: Two hundred female RA patients were enrolled and divided into two groups; non-contraception users (50 patients) and contraception users (150 patients). The latter group was further subdivided according to the method of contraceptive method used into: 89 intrauterine device (IUD)-users; 45 combined oral contraceptives (COC)-users; 16 injectable users. All patients underwent thorough history taking with special emphasis on contraception history, clinical examination, and assessment by routine laboratory tests, rheumatoid factor (RF) and antibodies to citrullinated protein antigens (ACPA). Rheumatoid arthritis disease activity was assessed using Disease Activity Score 28 using CRP (DAS28/ CRP), while RA disease severity was assessed using Rheumatoid Arthritis Severity Scale (RASS). Bilateral hand x-rays were done and interpreted by the Short Erosion Scale (SES).
Results: The percentage of ACPA seropositivity among IUD-users was 75.3%; the highest among all studied subgroups. IUD-users showed significantly higher ACPA titers (p=0.020), as well as longer disease duration (p=0.021) compared to other methods-users. The RASS was significantly higher in injectable users in comparison to other methods-users followed by the IUD-users (p=0.008). COC-users had the least RASS. However, there were no significant differences regarding DAS28/CRP or SES between different contraceptive methods-users. There was positive correlation between ACPA titers and RASS.
Conclusion: The increased ACPA positivity as well as higher ACPA titers in women who are currently IUD-users suggests a possible etiopathogenic role for IUD in onset and perpetuation of RA disease. Mechanisms by which IUD could increase RA-related autoimmunity risk were discussed. Whether cessation of IUD use in RA patients might improve their current state of disease need further study.
Lucyle Carmela D Abrasia
Southern Philippines Medical Center, Philippines
Title: A case report of bullous lupus erythematosus in a 39 year old female
Biography:
Lucyle Carmela D. Abrasia, RN, MD, was born in General Santos City, Philippines and is a graduate of San Pedro College where she obtained her Bachelor in Science inNursing. She had her medical degree at Davao Medical School Foundation, Inc. She trained in internal medicine at Southern Philippines Medical Center and currently onher third year in training. Dr. Abrasia is a member of Philippine Medical Association. She is currently residing in Davao City, Philippines.
Abstract:
Bullous systemic lupus erythematosus is a rare sub type of systemic lupus erythematosus (SLE) which occurs in less than 1% of patients with SLE. It is characterized by vesicular to bullous lesion with erythematous borders. Bullous lesion may be the first manifestation of SLE, requiring a high degree of clinical suspicion. This is case of a 38 year old female who came in due to generalized violaceous skin lesions associated with shortness of breath and body weakness. The patient initially manages as bullous pemphigoid. The patient eventually had onset of joint pains, oral ulcers, alopecia and body fatigue. Skin biopsy revealed interface dermatitis and direct immunofluorescence which resulted in strong granular deposits of IgG (+3), weak intermittent linear deposits of IgA (+1) and IgM (+/-) at the basement membrane zone supporting a diagnosis of bullous SLE. The patient was maintained on prednisone with no reported recurrence of skin lesions and other symptoms.
Michal A Rahat
Carmel Medical Center and Technion, Israel
Title: The role of the pro-angiogenic protein EMMPRIN in the pathogenesis of psoriatic arthritis
Biography:
Michal A Rahat studied the interactions between macrophages and other cell types (tumor cells, fibroblasts and endothelial cells), their regulation by the extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) and micro RNAs and their effect on macrophage function and involvement in processes such as inflammation, antigen presentation, angiogenesis, tissue repair and invasiveness/metastasis, in the context of solid tumors or inflammatory diseases. Recently, she has developed two vaccination approaches, using an antibody or an active peptide vaccination against a novel epitope in EMMPRIN and she now investigates the efficacy of these methods in inhibiting angiogenesis of autoimmune diseases or cancerous diseases in animal models. She currently serves as an Assistant Professor at the Faculty of Medicine, Technion-Israel Institute of Technology and as the Director of the Research Labs and the Head of the Immunotherapy Lab at the Carmel Medical Center.
Abstract:
Angiogenesis is an essential component in the pathophysiology of psoriatic arthritis (PsA). Extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147) is a multifunctional protein that enhances angiogenesis by inducing VEGF and MMPs. Using ELISA, we assessed the concentrations of angiogenic factors (EMMPRIN, VEGF, MMP-9, MMP-7, MMP-3, MMP-2, MMP-14) in serum of 56 PsA patients with active disease, 41 PsA patients in remission, 33 patients with active rheumatoid arthritis (RA) and 33 healthy controls. PsA patients demonstrated significantly elevated levels of serum EMMPRIN, MMP-7, MMP-14 compared to RA patients (p<0.001, p<0.01 p<0.01 respectively) and to controls (p<0.0001 p<0.01, p<0.01 respectively). The levels of VEGF (p<0.05), MMP-14 (p<0.05), MMP-2 (p<0.0001), TIMP-2 (p<0.001), OPG (p<0.001) and RANKL (p<0.001) were higher in PsA patients with active disease compared to patients in remission. Serum concentrations of MMP-9 were significantly lower in RA and PsA patients vs., controls (p<0.0001) with no significant difference between the two disease groups. To evaluate the mediating role of EMMPRIN in fibroblast macrophage interactions and angiogenesis, we co-cultured in vitro the human fibroblast HT1080 cell line with the human monocytic like U937 or Mono Mac 6 cell lines. Secretion of EMMPRIN, VEGF and MMP-9 were synergistically enhanced in the co-culture (p<0.01 for all three proteins relative to single cultures), and addition of the blocking anti-EMMPRIN antibody reduced VEGF (1.7-folds, p<0.001) and MMP-9 levels (1.4-folds, p<0.001) in the co-culture. Higher numbers of closed lumens were generated when the endothelial cell-line EaHy926 was incubated with supernatants derived from the co-cultures relative to each single culture (p<0.05) whereas, when EMMPRIN was blocked by the antibody, this number significantly decreased (p<0.05). EaHy926 cells incubated with the co-culture supernatants were more rapidly migrated to close a scratch, compared to cells where EMMPRIN was specifically blocked by antibody (p<0.05). Our results implicate EMMPRIN as an important mediator of angiogenesis promoting fibroblast monocytes interactions, suggesting it has a central role in the pathophysiology of PsA.
Biography:
Brij Bhushan Mehta pursued his PhD from the Department of Immunopathology at Post Graduate Institute of Medical Education and Research (PGIMER), India. His area of focus was to study pathogenesis of rheumatoid arthritis with project entitled “Modulation of extracellular matrix components relevant to rheumatoid arthritis”. During his PhD, he also worked on tumor biology project entitled “Correlation of full length variants and truncated fragments of osteopontin and tenascin c with histopathological characteristics of breast cancer”. Earlier, he worked on pathogenesis of malaria, as a Junior Research Fellow in project entitled “Identification and validation of new drug targets for selected pathogens”, at Institute of Microbial Technology (C.S.I.R.), Chandigarh, India for two years during February 2009 – March 2011. He also has seven years of research experience in biological science with various areas of focus like Immunology, Cell Biology, Protein re-engineering and Biochemistry, Molecular Biology and Microbiology and this motivates him to pursue career in the field of biological sciences associated with human healthcare.
Abstract:
Statement of the Problem: Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder characterized by progressive remodeling and degradation of extracellular matrix (ECM) in joint tissue leading to permanent bone deformity and loss of function. Matrix metalloproteinases (MMPs) are the major contributors to ECM degradation; elevated levels of MMPs correlate with the pathology of RA. Gelatinase A (MMP-2) is expressed by a large number of mesenchymal cells; whereas gelatinase B (MMP-9) is mainly expressed by macrophages and activated synovial fibroblasts. Studies have shown elevated MMP-2 and MMP-9 levels in synovial fluid (SF) of RA Patients. Several MMP inhibitors have been synthesized and tested in preclinical models of arthritis over the past one decade; however, no promising specific inhibitor of MMP-2 or MMP-9 has been developed so far. In the current study, we have targeted the catalytic domains of MMP-2 and MMP-9 by generating single chain variable fragment (scFv) antibodies against these domains.
Methodology & Theoretical Orientation: scFv antibodies were selected against these domains by antibody phage library based screening methods and characterized. In vitro assays of cell viability, proliferation, migration and collagen gel contraction assay (relevant to ECM remodeling during wound healing process) were conducted with and without antibodies using patient derived human synovial fibroblasts (HSF) and synovial fluid. Fibroblast/Cartilage co-culture experiments were done to assess the effect of antibodies on the degradation of cartilage by quantifying the amount of released glycosaminoglycans (GAGs) in culture supernatants.
Findings: Selected clone scFv M2-72, directed against MMP-2 was observed to neutralize the activity of MMPs in SF using an in vitro fluorogenic peptide assay. The antibody significantly inhibited the migration of HSF in response to patient derived SF in the transwell migration assay. scFv M2-72 significantly prevented cartilage degradation and further prevented collagen gel contraction and degradation. M2-72 may be a promising choice for RA treatment.
Stuart Porter
Lecturer University of Salford Manchester UK
Title: Understanding rheumatoid arthritis in one hour. Generating an evolving drop box flyer for use by undergraduate physiotherapy students
Biography:
I have 21 years of lecturing experience. My passion is rheumatology education. My PhD examined exercise behavior in Ankylosing spondylitis. I have written eight books that are now translated into eleven languages. I was a Chartered Physiotherapist within the NHS for 11 years. I was also the Physiotherapist to the England Women’s football team for three years. This was a unique and memorable experience and I was immensely proud to represent my country, working with such talented individuals both at home and during tours of countries including France, Denmark, Italy, Iceland, Bulgaria, and the Soviet Union. During the summer months I work at Corpus Christi College Cambridge where I am Medical Director of studies to international medical students at Corpus Christi College. I am a visiting lecturer in Brazil.
Abstract:
Statement of the Problem:
The time and academic pressures on UK undergraduate physiotherapy students increase each year. Students are now routinely expected to have a detailed knowledge of anatomy physiology, research methods keep an up to date portfolio and work with and have a knowledge of other professions. All of this with limited class contact time. This means that the time available to lecture on specific disease such as Rheumatoid arthritis is extremely limited. Student physiotherapists finding learning the pathology, immunology and management of RA extremely challenging as it is often the first systemic immunological disease they encounter in their undergraduate studies.
- The complexity of RA
- Our evolving understanding of the immune and cellular events of rheumatoid arthritis has led to the development of a considerable number of new developments that students need to be kept abreast of in an easily accessible format presented clearly but accurately.
- Powerpoint presentations and book chapters have their place but,
in an evolving topic such as rheumatology are often immediately outdated once delivered. Also, there are knowledge retention issues with PowerPoint (typically 15%) (Savoy et al 2009). I propose a flyer entitled “Rheumatoid arthritis- the story of a disease” presented in the format of a news article making it less dauting and more palatable to our students
- The flyer
The flyer can be found at
It is presented as a succinct but evidence-based guide to RA that will evolve as our knowledge of RA evolves, rather than students being given a one-off lecture they will be provided with this link which will be updated remotely as new genetic, epigenetic and pharmacological developments are made. This will be evaluated by online survey after each student log in episode to view the flyer.