title: Interactions of the complement system with molecules of extracellular matrix: relevance for joint diseases.
abstract: Rheumatoid arthritis (RA) is a highly disabling disease affecting all structures of the joint. Understanding the pathology behind the development of RA is essential for developing targeted therapeutic strategies as well as for developing novel markers to predict disease onset. Several molecules normally hidden within the cartilage tissue are exposed to complement components in the synovial fluid upon cartilage breakdown. Some of these have been shown to activate complement and toll-like receptors, which may enhance an already existing inflammatory response, thereby worsening the course of disease. Other cartilage-resident molecules have in contrast shown to possess complement-inhibitory properties. Knowledge about mechanisms behind pathological complement activation in the joints will hopefully lead to methods which allow us to distinguish patients with pathological complement activation from those where other inflammatory pathways are predominant. This will help to elucidate which patients will benefit from complement inhibitory therapies, which are thought to aid a specific subset of patients or patients at a certain stage of disease. Future challenges are to target the complement inhibition specifically to the joints to minimize systemic complement blockade.
authors.affiliation: Department of Laboratory Medicine, Division of Medical Protein Chemistry, Wallenberg Laboratory, Skåne University Hospital, Lund University, Sweden.
authors.forename: Kaisa E
authors.initials: KE
authors.lastname: Happonen
authors.forename: Dick
authors.initials: D
authors.lastname: Heinegård
authors.forename: Tore
authors.initials: T
authors.lastname: Saxne
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002356:Cartilage / Q000276:immunology / Q000473:pathology; D064236:Cartilage Oligomeric Matrix Protein; D003167:Complement Activation; D003165:Complement System Proteins / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007592:Joint Diseases / Q000276:immunology* / Q000378:metabolism; D000090263:Leucine-Rich Repeat Proteins; D064235:Matrilin Proteins; D011506:Proteins / Q000276:immunology / Q000378:metabolism; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D000090263:Leucine-Rich Repeat Proteins; D064235:Matrilin Proteins; D011506:Proteins; C577553:TSP5 protein, human; D051193:Toll-Like Receptors; D003165:Complement System Proteins