title: Trimer and tetramer complexes containing C1 esterase inhibitor, C1r and C1s, in serum and synovial fluid of patients with rheumatic disease.
abstract: During activation, the first component of complement C1q (C1r-C1s)2 is dissociated in conjunction with the formation of complexes containing C1 esterase inhibitor (C1-INH). Trimer complexes, with zymogen C1s associated with a firm C1-INH-C1r complex (C1-INH-C1r-C1s) can be distinguished from tetramer complexes C1-INH-C1r-C1s-C1-INH) in which C1-INH is firmly bound to both proteases. In the present study a two-stage electroimmunoassay was developed for the specific measurement of C1-INH-C1r-C1s. In the first step, C1-INH and its complexes were immunoprecipitated with anti-C1-INH during electrophoresis in the presence of Ca2+. In the second step, C1s contained in C1-INH-C1r-C1s was dissociated in the presence of EDTA and was measured by immunoprecipitation with anti-C1s. C1-INH-C1r-C1s were consistently found in normal sera. Normal sera did not contain C1-INH-C1r-C1s-C1-INH as assessed with a previously described ELISA procedure. Sera and synovial fluids from two groups of patients with inflammatory arthritis were investigated. In rheumatoid arthritis patients (n = 15) C1-INH-C1r-C1s complexes were usually found at high concentration both in serum and synovial fluid. C1-INH-C1r-C1s-C1-INH complexes were also present with values that were higher in synovial fluid than in serum, in accord with previous findings of classical pathway activation in the inflamed joints of the patients. Patients with spondylarthritic syndromes (n = 7) had serum and synovial fluid C1-INH-C1r-C1s concentrations that were comparable to those of the rheumatoid arthritis patients. If at all present, C1-INH-C1r-C1s-C1-INH were detected in trace amounts. Thus, C1 activation in patients with spondylarthritic syndromes appeared to be efficiently controlled at the C1r level. Distinguishing between C1-INH-C1r-C1s and C1-INH-C1r-C1s-C1-INH may prove of value in further studies of the activation and control of C1 in disease.
authors.affiliation: Department of Medical Microbiology, University of Lund, Sweden.
authors.forename: A B
authors.initials: AB
authors.lastname: Laurell
authors.forename: U
authors.initials: U
authors.lastname: Mårtensson
authors.forename: A G
authors.initials: AG
authors.lastname: Sjöholm
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology; D003174:Complement C1 Inactivator Proteins / Q000032:analysis*; D015923:Complement C1r / Q000032:analysis*; D003173:Complement C1s / Q000032:analysis*; D004560:Electricity; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D010003:Osteoarthritis / Q000276:immunology; D011817:Rabbits; D012216:Rheumatic Diseases / Q000276:immunology*; D013582:Synovial Fluid / Q000276:immunology*
chemical_list: D003174:Complement C1 Inactivator Proteins; D015923:Complement C1r; D003173:Complement C1s