REVIEW Proteomics in rheumatology: The beginning of a fairy tale? Stijn Lambrecht 1 , Kelly Tilleman 1 , Dirk Elewaut 2 and Dieter Deforce 1 1 Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium 2 Laboratory of Molecular Immunology and Inflammation, Department of Rheumatology, Ghent University Hospital, Ghent, Belgium One of the major challenges in proteome research is to translate its applications to the setting of human diseases. Proteomics in rheumatology is an area with marked potential including applications ranging from diagnostics, over therapeutic monitoring to discovery of new potential therapeutic targets. Biomarkers will be essential to discriminate between clinical similar rheumatic diseases, to monitor disease-states or to install the best appro- priate therapy. Especially in the field of rheumatology, analysis of specific genes and/or their expression products by pharmacogenetics/-genomics or pharmacoproteomics could be necessary to enable an effective, patient-tailored therapy. In rheumatology, direct examina- tion of proteins may be of utmost importance, as it is already known that PTMs, such as citrullination of proteins or peptides, may be involved in certain rheumatic diseases. The discovery and validation of antibodies directed against citrullinated proteins/peptides in rheumatic diseases using proteome analysis approaches has been described. Gel-free methods, SELDI-approaches and classic 2-DE approaches have been deployed on body fluids as well as on target tissues in different rheumatic diseases. Proteomics in rheuma- tology is on the rise and pilot studies have indicated that the application of proteomics- based technologies in rheumatic diseases appears to be an exciting example of translational research. Received: June 29, 2007 Revised: September 26, 2007 Accepted: September 26, 2007 Keywords: Arthritis / Biomarker / Citrullination / Rheumatology Proteomics Clin. Appl. 2008, 2, 411–419 411 1 Introduction Rheumatology is a discipline of internal medicine which diagnoses and manages a series of related diseases. The pri- marily targeted organs are the joints. It is therefore obvious that, in addition to serum, the joint tissues are the most fre- quently investigated by proteomics in rheumatology re- search, although other organs such as kidneys, lungs, and skin may also be affected. 1.1 Joint anatomy A joint is an organ where two or more bones are “connected” with each other. Joints can be classified based on histological features. Three types of joints are generally discriminated: the fibrous joints, cartilaginous joints and synovial joints. The synovial joints (or diarthroidal joints) are the joints affected by arthritis, the most common symptom in rheu- matology. Synovial joints are surrounded by a capsule that defines the boundary between articular and peri-articular tissues [1] (Fig. 1). The stability of the joint is provided by the bones, ligaments, joint capsule, and the muscles. The articulating Correspondence: Professor Dieter Deforce, Laboratory of Phar- maceutical Biotechnology, Harelbekestraat 72, B-9000 Ghent, Belgium E-mail: dieter.deforce@ugent.be Fax: 132-9-220-6688 Abbreviations: ACPA, anticitrullinated protein/peptide anti- bodies; ECM, extracellular matrix; FLS, fibroblast-like synovio- cytes; OA, osteoarthritis; PAD, peptidylarginine deiminase; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SpA, spondylarthropathies DOI 10.1002/prca.200780084  2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.clinical.proteomics-journal.com