Effect of whole and fractionated intravenous immunoglobulin on complement in vitro.
Intravenous immunoglobulins (IVIG) are increasingly used for treatment of inflammatory diseases, and the modulation of complement may contribute to some of its beneficial effects. IVIG may bind C1q and activated C3 and C4, and enhance inactivation of C3b. We have previously shown that IVIG inhibited complement-mediated lysis solely via its Fc part through interaction with the classical pathway. In the present study we have investigated whole IVIG (Octagam, and Sandoglobulin) and the monomer, dimer and multimer fractions of Octagam with respect to complement activation in serum and inhibition of complement lysis of red cells. The isolated fractions were found to be stable, homogeneous (monomer, dimer or multimer) and pure (virtually only IgG). Both whole IVIG and its fractions significantly activated complement in serum and inhibited hemolysis compared with human albumin. These effects were most pronounced in the monomer, less in the multimer and least in the dimer fraction. The complement activation was shown to be mediated through the classical pathway since formation of C1rs-C1inh complexes and C4bc were increased, in contrast to Bb. Surprisingly, heat aggregation of Octagam was not followed by a corresponding increase in complement activation, as would be expected, unless it was dialysed before heating, suggesting that it is stabilized to avoid excess activation. In conclusion, the results support the hypothesis that IVIG causes a mild activation of complement in vitro. We suggest that this effect may contribute to the complement inhibitory properties of IVIG by diverting complement deposition from the target to the fluid phase.
Mollnes
T E
TE
Department of Immunology and Transfusion Medicine, Nordland Central Hospital, Bodø, Norway. tomeirik@fagmed.uit.no
Andreassen
I H
IH
Høgåsen
K
K
Hack
C E
CE
Harboe
M
M
D000818:Animals; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D015941:Complement Hemolytic Activity Assay; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes; D006361:Heating; D006461:Hemolysis / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D007136:Immunoglobulins / Q000276:immunology* / Q000302:isolation & purification; D016756:Immunoglobulins, Intravenous / Q000276:immunology*; D012756:Sheep
D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D003165:Complement System Proteins