Immunoglobulin Therapy: Replacement and Immunomodulation

Immunoglobulin (Ig) replacement therapy is an important live-saving treatment modality for patients with primary humoral immune deficiency. The goal of treatment is to provide a broad spectrum of antibodies to prevent infections; inflammatory injury to vital organs, such as the lung; and chronic long-term complications. Recent studies have suggested that therapy with replacement Ig should be at doses needed to keep the patient free of infections, often referred to as the IgG “biological” trough or steady-state serum IgG level. Ig can be given intramuscularly, intravenously, or subcutaneously. Subcutaneous administration has proven to be safe and is a good alternative in most patients, especially those experiencing systemic side effects when treatment is given by the intravenous route. Generally, Ig replacement therapy is considered safe. Side effects are usually mild and treatable with premedication. Good manufacturing practices, improved screening of plasma donors, testing of the source plasma, and additional viral inactivation and removal steps have made Ig products a better and safer plasma-derived product. Ig therapy is an effective treatment for a wide spectrum of autoimmune and inflammatory diseases. At present, intravenous Ig (IVIG) is approved by the US Food and Drug Administration (FDA) for only some autoimmune and inflammatory diseases. Although no single mechanism can explain the beneficial effects of IVIG, it is likely that several mechanisms of action working together are responsible for the effects of IVIG in many of the autoimmune diseases. A better understanding of the pathogenic mechanisms involved in these diseases will undoubtedly lead to more effective therapy with IVIG and, in the future, to a more specific, modified form of this biological product.