Immunoglobulin Replacement

The concept of transfer of protection dates back to 1890, when Emil Behring and Shibasaburo Kitasato discovered that guinea pigs injected with killed diphtheria or tetanus bacilli developed a soluble substance that could be transferred to a second guinea pig to provide protection for an infectious challenge. This concept was extended to humans in the 1930s, but side effects were common. Immunoglobulin purification began when Cohn developed an ethanol fractionation method to separate plasma proteins into stable fractions in 1946. In 1952, Bruton described the first case of agammaglobulinemia and showed that subcutaneous injections with Cohn fraction II was an effective treatment. This landmark case began the modern era of immunoglobulin replacement. Many of the early cases of immunoglobulin replacement utilized intramuscular injections, because the products contained prekallikrein and other biologically active components and intravenous administration led to fever and cardiovascular symptoms. The Swiss Red Cross laboratories developed methods to adapt the Cohn fraction II for use intravenously by using exchange chromatography, and in 1981 the first commercial intravenous immunoglobulin (IVIG) became available in the United States. Today, patients have a wide variety of subcutaneous or intravenous immunoglobulin products and patients receive immunoglobulin replacement in their own homes, thus facilitating a higher quality of life. In this chapter, the uses of immunoglobulin and adverse events are reviewed.