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Synovial Macrophages as a Biomarker of Response to Therapeutic Intervention in Rheumatoid Arthritis: Standardization and Consistency Across Centers
BARRY BRESNIHAN, DANIELLE M. GERLAG, TERENCE ROONEY, TOM J.M. SMEETS, CARLA A. WIJBRANDTS, DAVID BOYLE, OLIVER FITZGERALD, BRUCE W. KIRKHAM, IAIN B. McINNES, MALCOLM SMITH, ANN-KRISTIN ULFGREN, DOUGLAS J. VEALE, and PAUL P. TAK ABSTRACT. Successive studies from one academic center (Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands) have consistently suggested that synovial tissue expression of sublining macrophages may be a biomarker of clinical response to therapeutic intervention in rheumatoid arthritis (RA) clinical trials. A proof-of-concept, randomized clinical trial was completed at a second academic center (St. Vincent's University Hospital, Dublin, Ireland), and the relationship between the change in disease activity and the change in sublining macrophages in distinct treatment cohorts was determined. The preliminary findings were not conclusive, but appeared to support a role for sublining CD68+ macrophages as a biomarker of clinical response to therapeutic intervention in cohorts of patients with RA. (J Rheumatol 2007;34:620-2) Key Indexing Terms: SYNOVIUM From the Department of Rheumatology, St. Vincent's University Hospital, and The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland; Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Division of Rheumatology, Allergy and Immunology, University of California at San Diego, La Jolla, California, USA; Guy's and St. Thomas' Hospital, London; Center for Rheumatic Diseases, University of Glasgow, Glasgow, UK; Rheumatology Research Unit, Repatriation General Hospital, and Flinders University, Adelaide, Australia; and the Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden. Supported by the European Community FP6 funding (Autocure). B. Bresnihan, MD, FRCP, Professor of Rheumatology, Department of Rheumatology, St. Vincent's University Hospital and The Conway Institute of Biomolecular and Biomedical Research, University College Dublin; D.M. Gerlag, MD, Assistant Professor of Medicine, Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam; T. Rooney, MB, MRCPI, Research Fellow, Department of Rheumatology, St. Vincent's University Hospital; T.J.M. Smeets, PhD, Project Scientist, Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam; C.A. Wijbrandts, MD, Research Fellow, Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam; D. Boyle, BA, Scientist, Division of Rheumatology, Allergy and Immunology, University of California at San Diego; O. FitzGerald, MD, FRCP, Professor of Rheumatology, Department of Rheumatology, St. Vincent's University Hospital, and The Conway Institute of Biomolecular and Biomedical Research, University College Dublin; B.W. Kirkham, MD, FRCP, FRACP, Clinical Lead, Rheumatology/Lupus, Department of Rheumatology, Guy's and St. Thomas' Hospital; I.B. McInnes, FRCP, PhD, Professor of Experimental Medicine, University of Glasgow; M.D. Smith, MD, PhD, Professor of Rheumatology, Rheumatology Research Unit, Repatriation General Hospital and Flinders University; A-K. Ulfgren, PhD, Senior Scientist, Rheumatology Unit, Department of Medicine, Karolinska University Hospital; D.J. Veale, MD, FRCP, Consultant Rheumatologist, Department of Rheumatology, St. Vincent's University Hospital and The Conway Institute of Biomolecular and Biomedical Research, University College Dublin; P.P. Tak, MD, PhD, Professor of Medicine, Director, Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam. Address reprint requests to Prof. B. Bresnihan, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. E-mail: B.Bresnihan@svcpc.ie
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