Purification and characterization of IgG immunoconglutinins from patients with systemic lupus erythematosus: implications for a regulatory function.
The levels of IgG immunoconglutinins in plasma from patients with rheumatoid arthritis, systemic lupus erythematosus and primary biliary cirrhosis were monitored by ELISA. High levels of IgG immunoconglutinins were found mainly in plasma from patients with systemic lupus erythematosus. These immunoconglutinins bound to microtitre plate-fixed C3, C3b and C3c but poorly to C3d. This binding was inhibited by particle-bound C3b and iC3b but not by the corresponding soluble fragments. Furthermore, Western blot analysis revealed no immunoconglutinin-binding to reduced C3 peptides and no binding was shown to soluble C3 alpha and beta chain by ELISA. IgG immunoconglutinins were purified from three plasma specimens by affinity chromatography on activated thiol sepharose ATS/C3 fragments. Two immunoconglutinin preparations that preferentially recognize ATS-C3b, inhibited C5-convertase function by 50-100% while one immunoconglutinin that recognized ATS-C3d,g had no effect. The two former immunoconglutinins also inhibited all three factor I cleavages in C3 alpha chain but the latter inhibited only the third cleavage. None of the immunoconglutinins affected the binding of complement-coated anti-BSA/BSA complexes to CR1 (CD35) on human erythrocytes, but the two immunoconglutinins that inhibited all factor I cleavages also inhibited the factor I-induced release of anti-BSA/BSA complexes from CR1. The results show that immunoconglutinins recognize specific epitopes on bound C3 fragments and that they are able to modulate C3-mediated functions.
Nilsson
B
B
Department of Clinical Immunology and Transfusion Medicine, University Hospital, Uppsala, Sweden.
Ekdahl
K N
KN
Svarvare
M
M
Bjelle
A
A
Nilsson
U R
UR
D000918:Antibody Specificity; D001323:Autoantibodies / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology; D003176:Complement C3 / Q000276:immunology; D050577:Complement C3-C5 Convertases / Q000037:antagonists & inhibitors; D004797:Enzyme-Linked Immunosorbent Assay; D005340:Fibrinogen / Q000037:antagonists & inhibitors; D006801:Humans; D037561:Immunoconglutinins; D007074:Immunoglobulin G / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology*; D007136:Immunoglobulins / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D011951:Receptors, Complement / Q000378:metabolism; D017463:Receptors, Complement 3b
D001323:Autoantibodies; D003176:Complement C3; D037561:Immunoconglutinins; D007074:Immunoglobulin G; D007136:Immunoglobulins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D005340:Fibrinogen; D050577:Complement C3-C5 Convertases