title: Humoral autoreactivity directed against surfactant protein-A (SP-A) in rheumatoid arthritis synovial fluids.
abstract: SP-A is found principally in the lung, and has been associated with lamellar bodies also found in the synovial joint. Both SP-A and C1q contain collagen-like regions, and SP-A and C1q have some structural similarities, both having a globular head region and a collagen-like tail. Here we are able to show that (i) autoreactivity to SP-A, as expressed by IgG and IgM autoantibodies, is present in synovial fluid (SF) isolated from patients with rheumatoid arthritis (RA); (ii) in absorption experiments only a limited degree of cross-reactivity between autoantibodies reactive with C1q and SP-A is observed; (iii) there is no cross-reactivity between autoantibodies reactive with type II collagen (CII) and those reactive with SP-A or C1q; (iv) autoantibodies react with polymeric (dimers and larger) SP-A, but not with monomeric SP-A subunits, indicating that a degree of quaternary structure is required for antibody binding. Unlike CII, which not accessible in the normal joint, both SP-A and C1q are available within the SF in patients with RA and may therefore provide antigens driving an autoimmune response directed against collagen-like structures.
authors.affiliation: Institute of Medical Microbiology & Hygiene, Johannes Gutenberg University, Mainz, Germany.
authors.forename: P K
authors.initials: PK
authors.lastname: Trinder
authors.forename: T P
authors.initials: TP
authors.lastname: Hickling
authors.forename: R B
authors.initials: RB
authors.lastname: Sim
authors.forename: D
authors.initials: D
authors.lastname: Brackertz
authors.forename: M
authors.initials: M
authors.lastname: Loos
authors.forename: M J
authors.initials: MJ
authors.lastname: Maeurer
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000096:biosynthesis* / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology*; D001666:Binding Sites, Antibody; D002645:Chickens; D003094:Collagen / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D015922:Complement C1q / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D007075:Immunoglobulin M / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D007719:Knee Joint / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011510:Proteolipids / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D013582:Synovial Fluid / Q000737:chemistry / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010455:Peptides; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D015922:Complement C1q; D003094:Collagen