Intravenous immunoglobulin (IVIG) is a polyclonal mixture of immunoglobulin G (IgG) antibodies that can be administered intravenously. IVIG is used primarily as replacement therapy in a variety of disorders marked by IgG deficiency. In large doses, IVIG has anti-inflammatory and immune-modulatory functions and plays a role in the treatment of various autoimmune disorders.
There are at least eleven licensed IVIG products commercially available in the United States, in addition to four preparations licensed for subcutaneous administration. IVIG is manufactured from pooled human plasma obtained from thousands of donors who are screened for infection with human immunodeficiency virus (HIV) 1 and 2, hepatitis B and C, and syphilis. Besides donor screening, most IVIG preparations undergo multiple purification steps that further reduce the potential risk of viral contamination. These purification steps involve ethanol fractionation followed by chromatography, pasteurization, solvent/detergent treatment, protease treatment, acid treatment, or low-salt treatment. The final product is stabilized with sugars such as sucrose, amino acids such as glycine, or human albumin. All IVIG preparations have trace amounts of IgA antibodies. Although there have been no documented cases of HIV transmission from IVIG, more than 200 patients had documented hepatitis C transmission from IVIG in the early 1990s, before screening for hepatitis C became standard.1
The mechanisms of action of IVIG are multiple and complex and have not been completely elucidated. The prophylactic effects of IVIG against infection are easily explained, as IVIG contains high titer antibodies against common pathogens, including viruses such as varicella, and bacteria such as Streptococcus pneumoniae. Prophylaxis against infection can usually be achieved with “replacement” doses of approximately 0.4 g/kg.
The anti-inflammatory activity of IVIG is less well understood, and multiple theories have been proposed. To achieve an anti-inflammatory effect, IVIG is usually used at doses of 1 to 2 g/kg. Activation of inhibitory Fc receptors and down-regulation of activating Fc receptors, binding to serum complement proteins and cytokines, inhibition of pathogenic autoantibodies, and modulation of T- and B-cell function are among the described roles.2 A series of recent studies suggests that only a small fraction of the immunoglobulins, modified by the addition of sialic acid, are responsible for IVIG’s anti-inflammatory activity.3,4 Work done in animal models suggests that these modified immunoglobulins activate an anti-inflammatory pathway on dendritic cells and macrophages. High-dose IVIG may also induce plasma cells to undergo apoptosis.5
The US Food and Drug Administration (FDA) has approved seven applications of IVIG or SCIG: primary immunodeficiency, acute immune thrombocytopenic purpura, secondary immunodeficiency due to leukemia, prevention of infection and graft-versus-host disease in bone marrow or stem cell transplant recipients, prevention of infection in pediatric HIV disease, chronic inflammatory demyelinating polyneuropathy, and prevention of coronary sequelae of Kawasaki disease. Dosing recommendations for these approved indications are provided in Table 50-1...