In vitro comparison of the complement-scavenging capacity of different intravenous immunoglobulin preparations.
OBJECTIVE
Complement inhibition is considered important in the mechanism of action of intravenous immunoglobulin (IVIG) in a number of inflammatory and autoimmune disorders. The capacity of different IVIG preparations to 'scavenge' activated C3 and thereby inhibit complement activation was assessed by a new in vitro assay.


METHODS
Diluted human serum as a complement source, with or without addition of different concentrations of IVIG, was incubated in microtitre plates coated with heat-aggregated human IgG. Complement scavenging was measured by detecting reduced C3 binding and determining fluid phase C3b-IgG complex formation. Complement activation induced by the IVIG preparations was measured as C5a formation.


RESULTS
All IVIG preparations exhibited a dose-dependent inhibition of C3b deposition, correlating strongly with binding of C3b to fluid-phase IgG, but the extent of complement scavenging varied considerably between different IVIG preparations. At an IVIG concentration of 0.9 mg/ml, the inhibition of C3b deposition ranged from 72 +/- 16% to 22 +/- 4.1%. The reduction of C3b deposition on the complement-activating surface was not due to IVIG-induced complement activation in the fluid phase, as shown by the low C5a formation in the presence of serum.


CONCLUSIONS
In vitro analysis allows comparison of the complement-inhibitory properties of IVIG preparations. The extent of complement scavenging varies between the products.
Spycher
M
M
CSL Behring AG, Bern, Switzerland.
Matozan
K
K
Minnig
K
K
Zehnder
R
R
Miescher
S
S
Hoefferer
L
L
Rieben
R
R
D003167:Complement Activation; D015926:Complement C3a / Q000737:chemistry* / Q000276:immunology; D015936:Complement C5a / Q000032:analysis* / Q000276:immunology; D003168:Complement Fixation Tests / Q000379:methods; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000032:analysis* / Q000276:immunology
D016756:Immunoglobulins, Intravenous; D015926:Complement C3a; D015936:Complement C5a