Immunochemical-based assays in the bioanalysis of immunoglobulins

Intravenous immunoglobulin (IVIG) preparations consist of IgG derived from a pool of human plasma of healthy individuals and have been used as routine treatment of patients with primary and secondary immunodeficiencies, autoimmune, and/or inflammatory diseases. Emergence of new infectious agents and development of antibiotic resistance in many bacteria have posed serious problems in the treatment of infections. Since IVIGs contain natural antibodies that occur in the healthy population, their administration to immunocompromised hosts either as a prophylactic agent or as complementary treatment to the usual antimicrobial treatment have been studied. Contradictory results obtained by several clinical studies in respect to the clinical efficacy of IVIGs have in part been ascribed to the poor characterization of IVIG preparations in terms of their specific antibody content against the various pathogenic microorganisms. Immunoassays constitute a promising tool for bioanalysis of IVIGs thanks to the high sensitivity, repeatability and ease of implementation. Ensuring high selectivity, enzyme immunoassays have been used for determination of the levels of pathogen-specific antibodies in IVIG preparations. In this review, the application of immunoassays monitoring such specific antibodies in IVIGs and the relationship of estimated titers with their in vitro opsonic activity are summarized. The relationship of the content of specific antibodies in IVIGs and their functional efficacy with the outcome of clinical studies including patients with primary immunodeficiencies and premature neonates treated with IVIGs is also discussed.