Effect of intravenous immunoglobulin therapy on plasma complement

Area of Science:

• Immunology
• Complement System Biology

Background:

• Primary humoral immunodeficiency is characterized by impaired antibody production.
• Intravenous immunoglobulin (IVIG) therapy is a cornerstone treatment for various immunodeficiencies.
• The impact of IVIG on the complement system and immune complex formation requires further elucidation.

Purpose of the Study:

• To investigate the effects of Sandoglobulin (pH4-treated IVIG) on complement activation and circulating immune complexes (CIC).
• To assess changes in complement components (C4, C3, factor B, C3dg) and C1q levels post-IVIG infusion.
• To explore the relationship between C1q levels, IgG concentration, and IVIG therapy in hypogammaglobulinemia.

Main Methods:

• Studied 10 patients with primary humoral immunodeficiency and 12 healthy volunteers.
• Administered 9g of pH4-treated IVIG preparation (Sandoglobulin).
• Measured total hemolytic complement activity, plasma C4, C3, factor B, C3dg fragments, and CIC (via 125I-C1q binding) before and after infusion. Assessed C1q concentrations pre- and post-therapy.

Main Results:

• No significant changes in total hemolytic complement activity or C4, C3, factor B levels were observed.
• Marked increases in C3dg fragments were noted in some individuals in both groups immediately post-infusion.
• Initially low C1q concentrations in immunodeficient patients correlated with pre-infusion IgG levels and significantly increased 24 hours after IVIG therapy.
• In vitro studies showed no spontaneous anticomplementary activity or immune aggregate formation from the IVIG preparation.

Conclusions:

• IVIG infusions can lead to moderate in vivo complement activation, indicated by elevated C3dg fragments.
• Partial C1q deficiency in hypogammaglobulinemia is associated with IgG levels.
• Immunoglobulin substitution therapy effectively corrects C1q deficiency in hypogammaglobulinemia.