ABSTRACT
Properties With few exceptions, attempts at intravenous usage of intramuscular immunoglobulin products in persons suffering from acute infections, usually children, had immediate and severe anaphylactic or anaphylactoid reactions (22,102,103). A primary cause for these severe adverse reactions was found by Barandun and colleagues to be due to the tendency for purified IgG molecules to aggregate. Both aggregated IgG and contaminating IgM were believed to be responsible for high anticomplement activity (104). While working in close cooperation with the Swiss Red Cross Laboratories, Barandun et al. first formulated IgG preparations at low pH (- 4.0) isolated in the presence of trace amounts of pepsin in order to minimize reaggregation. They then listed the desired criteria for an optimal NIG. Among these were: (1) maintenance of native structure and functional activities; (2) the entire spectrum of lgG antibodies present in a large representative blood donor population (i.e., large plasma pools); (3) all four IgG subclasses in physiological proportions; and (4) no infectious agents, aggregates, or other detrimental substances (105). Later. these properties were mandated for IVIG preparations by a World Health Organization (WHO) panel of experts (106). The foundation for immunoglobulin therapy was consequently laid, using the formulation developed by Barandun and colleagues. Since then, a large number of standard IVIG (and a limited number of HYPERNIG) products have been accepted as standard therapy for a variety of therapeutic and/or prophylactic benefits including secondary immunodeficiencies and autoimmune diseases.
