Intravenous Immune Globulin Infusion Research Articles

New uses of intravenous immune globulin in newborn infants

Preterm infants are hypogammaglobulinemic at birth, a condition that worsens during the first several weeks of life. It has been postulated that periodic infusions of intravenous immune globulin in preterm infants might prevent systemic infections after age 7 days, but clinical trials have been inconclusive. To test this hypothesis in neonates weighing 500 to 1750 g at birth, a multicenter, randomized, double-blind, placebo-controlled trial was initiated. Either intravenous immune globulin (500 mg/kg) (284 infants) or placebo (5% albumin-normal saline, 10 ml/kg) (293 infants) was infused periodically for 8 weeks. Infusions were well tolerated. Mortality (4%) was similar in both groups. However, the incidence of systemic infection was significantly reduced in the treatment group, but only in those weighing less than 1500 g. More than 80% of infections were bacterial; half were caused by staphylococci. Standard use of intravenous immune globulin in preterm infants looks promising but must await full analysis of data from this and another ongoing multicenter trial.

Potential Use of Intravenous Immune Globulin for Group B Streptococcal Infection

Several lines of evidence suggest that passive immunization as adjunctive therapy for or prevention of group B streptococcal (GBS) sepsis in neonates will require the use of preparations of human intravenous immune globulin (IVIG) that are hyperimmune for protective antibodies to GBS. Results from both in vitro and in vivo experiments utilizing commercially available IVIG preparations suggest that the doses necessary for achieving levels of pathogen-specific antibody capable of promoting efficient opsonization and phagocytosis of GBS may be prohibitive. Several laboratories have reported that standard IVIG preparations contain only modest levels of antibodies to the four capsular polysaccharides of GBS (the protective moieties), are variable in their effect on in vitro opsonophagocytosis by dose and method of preparation, and are significantly less protective in animal models than is IVIG prepared from adults immunized with GBS polysaccharide vaccines. Further, when we gave a single infusion of standard IVIG at a dose of either 500 or 750 mg/kg to 10 premature neonates during the first week of life, opsonophagocytosis of type III GBS by their sera and adult neutrophils was observed only when high levels of specific antibody were achieved, levels only transiently achieved in nonimmune infants. Commercial preparation of human immune globulin hyperimmune for GBS will be required for optimal adjunctive therapy in patients with sepsis due to GBS and for the possible prevention of late-onset infant disease.

Modulation of Fc receptor clearance and antiplatelet antibodies as a consequence of intravenous immune globulin infusion in patients with immune thrombocytopenic purpura

In 1981 Paul Imbach first reported the usefulness of intravenous immune globulin infusions in the treatment of children with immune thrombocytopenic purpura. Other studies have shown that intravenous immune globulin was associated with the fastest platelet increase of any therapy, confirming the initial observation in children and adults. We and other investigators have used intravenous immune globulin as a maintenance therapy and speculated that repeated single infusions might have a curative value, in addition to an acute effect. The best-defined mechanism of intravenous immune globulin in this model autoimmune disease is Fc receptor blockade. This was first demonstrated by a slowing of antibody-coated, chromium-labeled red blood cell survival. Subsequent confirmation has come from the use of intravenous anti-D and a monoclonal anti-FcRIII that has been used in patients refractory to treatment. In vitro studies have demonstrated alteration in Fc receptor expression on circulating cells, and this mechanism is presumed to be related intimately to the acute platelet increase seen after intravenous immune globulin. Studies with the latest platelet antibody methodology do not support interference with binding of antiplatelet antibodies as an important mechanism, but there are in vitro data to support this hypothesis. Another leading hypothesis is that intravenous immune globulin decreases the production of autoantibodies. Clinically, this has been suspected in immune thrombocytopenic purpura in which there are apparent improvements in patients with chronic disease, but no controlled studies have been performed to verify this. In acquired hemophilia and von Willebrand's disease, however, it seems quite clear that there is direct neutralization of autoanti-factor VIII antibodies by intravenous immune globulin by a presumed Fab-mediated anti-idiotype mechanism. This hypothesis has appeal and has been postulated on the basis of in vitro studies, as well as looking directly at the B cell. Another study supporting this mechanism showed that intravenous immune globulin preparations with altered Fc portions still mediate some platelet increase, even if not as much as intact IgG molecules. It remains unclear whether any effects that are the result of a lower level of autoantibody could be mediated through T cells or macrophages, rather than having direct action on the B cell. In any event, these findings strongly support the hypothesis that decreased levels of autoantibody lead to intermediate (weeks) and long-term (months to years) responses after intravenous immune globulin treatment.