Normalization of serum C1q after intravenous immunoglobulin infusions in hypogammaglobulinemia: dependence upon methods of immunoglobulin preparation

Abstract

Low levels of serum complement subcomponent C1q may accompany primary humoral immunodeficiency diseases such as sex-linked agammaglobulinemia, severe combined immunodeficiency, and common varied immunodeficiency. This selective depression of C1q is proportional to the degree of hypogammaglobulinemia, and is corrected in severe combined immunodeficiency by bone marrow transplantation or in hypogammaglobulinemia by immunoglobulin infusions, possibly because C1q is stabilized by IgG by reversible interactions which reduce extravascular degradation. In this study it is shown that a pH 4.0 treated intravenous gamma-globulin (ivGG) and a reduced and alkylated ivGG can equally increase levels of serum IgG, but that only the pH 4.0 preparation can raise C1q levels into the normal range. These findings show that some of the methods used to produce immunoglobulins suitable for intravenous use may hinder the ability of these molecules to stabilize Clq. The clinical implications of this observation remain unclear.