IgG dimers in multidonor-derived immunoglobulins: aspects of generation and function

Immunoglobulin G (IgG) concentrates for therapeutic purposes, like passive immunotherapy, supplementation in inherited or acquired deficiencies or immunomodulation, are prepared from multidonor-derived plasma pools. They usually contain varying amounts of dimeric IgG. The essential factor influencing dimer formation is the pool size; in addition, molecular properties of IgG and a variety of production process- and formulation-specific parameters are important. Numerous experimental findings suggest that dimers are predominantly generated by interactions of idiotypic and anti-idiotypic antibodies (Ids, anti-Ids). Ab-inherent crossreactivity, frequency distribution of both the affinities for particular Id-anti-Id interactions and the corresponding dimer concentrations still have to be elucidated. All these parameters influencing molecular features and functional activity of IgG dimers hamper the assay-dependent measurement of biological efficacy and correlation of total IgG content. A more detailed understanding may help to better control the dual nature of dimer-dependent biological activity comprising both undesirable (e.g., hypotension) and desirable effects of dimeric IgG (blockade of the reticuloendothelial system, RES, in immune thrombocytopenic purpura, ITP). These effects are detectable in in vitro and in vivo models and are thought to be of relevance for humans.