title: Reduced erythrocyte CR1 (CD 35) receptor function and complement opsonization in factor I-deficient patients is restored by plasma infusion.
abstract: Erythrocytes (E) from three factor I-deficient patients were investigated for surface-bound complement factors and CR1 (CD 35) expression and function. The E were coated with C4b, C3b, and factor H. Following plasma infusion or in vitro incubation of the patients' E with normal human serum (NHS) or purified factor I, cell-bound C4b and C3b could no longer be detected. The E now expressed C3d, and factor H was unaffected, indicating that factor H was bound to the C3d part of the C3b molecules, providing the co-factor for effective cleavage of E-bound C3b when purified factor I was added. The binding of monoclonal anti-CR1 antibodies (M710) to the patients' E was markedly reduced compared with control E, and was not normalized by treatment with NHS, probably because covalently bound C3d/factor H interfered with the binding of M710. By contrast, the reduced ability of the patients' E-CR1 to bind complement-opsonized immune complexes (IC) was normalized after plasma infusion. This shows that the impaired CR1 function was acquired and emphasizes the importance of performing functional CR1 assays. Complement opsonization of IC for binding to normal E was severely compromised in the patients' sera due to consumption of factor B and C3. After plasma infusion the opsonization capacity of the patients' sera was restored. Thus, two mechanisms of importance for normal clearance of IC were compromised in factor I-deficient patients: (1) the opsonization of IC for binding to E-CR1, and (2) the capacity of E-CR1 to bind opsonized complexes. Both dysfunctions were temporarily corrected by plasma infusion.
authors.affiliation: Institute of Medical Microbiology, Odense University, Denmark.
authors.forename: H H
authors.initials: HH
authors.lastname: Jepsen
authors.forename: B
authors.initials: B
authors.lastname: Teisner
authors.forename: J M
authors.initials: JM
authors.lastname: Rasmussen
authors.forename: S E
authors.initials: SE
authors.lastname: Svehag
mesh_terms: D000328:Adult; D000347:Afibrinogenemia / Q000276:immunology* / Q000628:therapy; D000936:Antigen-Antibody Complex / Q000276:immunology; D001803:Blood Transfusion; D003167:Complement Activation; D003180:Complement C3b Inactivator Proteins / Q000032:analysis; D017242:Complement Factor H; D003165:Complement System Proteins / Q000276:immunology*; D004533:Egtazic Acid / Q000494:pharmacology; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D010587:Phagocytosis; D011951:Receptors, Complement / Q000502:physiology*; D017463:Receptors, Complement 3b
chemical_list: D000936:Antigen-Antibody Complex; C493495:CFH protein, human; D003180:Complement C3b Inactivator Proteins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D004533:Egtazic Acid; D017242:Complement Factor H; D003165:Complement System Proteins