Anti-Inﬂammatory Actions of Intravenous Immunoglobulin
Falk Nimmerjahn1 and Jeffrey V. Ravetch2
Laboratory of Experimental Immunology and Immunotherapy, Nikolaus-Fiebiger-Center for Molecular Medicine, University ofErlangen-Nuremberg, 91054 Erlangen, Germany; email: firstname.lastname@example.org Laboratory for Molecular Genetics and Immunology, Rockefeller University, New York, New York 10021; email: email@example.com
Annu. Rev. Immunol. 2008. 26:513–33 The Annual Review of Immunology is online at immunol.annualreviews.org This article’s doi: 10.1146/annurev.immunol.26.021607.090232 Copyright c 2008 byAnnual Reviews. All rights reserved 0732-0582/08/0423-0513$20.00
Fc receptor, inﬂammation, glycosylation, autoimmunity, autoantibody, sialic acid, IVIG
The remarkable success story of the therapeutic application of pooled immunoglobulin G (IgG) preparations from thousands of donors, the so-called intravenous IgG (IVIG) therapy, to patients with a variety of hematologicaland immunological disorders began more than half a century ago. Since then, the use of this primary blood product has increased constantly, resulting in the serious danger of shortages in supply. Despite its widespread use and therapeutic success, the mechanisms of action, especially of the antiinﬂammatory activity, are only beginning to be understood. In this review, we summarize the clinical useof IVIG for different diseases and discuss recent data on the molecular mechanisms that might explain how this potent drug mediates its activity in vivo.
IgG: immunoglobulin G IVIG: intravenous IgG therapy ITP: idiopathic thrombocytopenic purpura
Annu. Rev. Immunol. 2008.26:513-533. Downloaded from arjournals.annualreviews.org by Universidad Nacional Autonoma de Mexicoon 10/02/08. For personal use only.
Immunoglobulins together with T cells are the key mediators of adaptive immunity, and deﬁciencies in either of these two arms of the adaptive immune system can result in a heightened susceptibility to bacterial, fungal, or viral infections. A variety of situations can lead to a constant or transient deﬁciency in immunoglobulins, including primaryimmunodeﬁciencies, such as several X-linked agammaglobulinemias and common variable immunodeﬁciencies (CVID) (1–3). In addition, hypogammaglobulinemic phenotypes can be caused by viral infections (for example with HIV), in the course of B cell malignancies, or after bone marrow transplantation (4–9). Thus, replacement of immunoglobulin levels, especially of the immunoglobulin G (IgG) isotype, by administrationof pooled serum from healthy donors—IVIG (intravenous IgG) as a therapeutic agent—occurred more than 50 years ago. Since then, IVIG use has increased exponentially, although its therapeutic effectiveness in most of these different diseases has not been rigorously addressed, in part because of the variety of diseases it is used to treat and
in part because extant studies include low patientnumbers. The popularity of IVIG in the clinic and in research is exempliﬁed by the 360 hits that a PubMed search for IVIG yielded in 2007, when we wrote this review. The two major clinical indications for which IVIG is used are IgG replacement therapy and antiinﬂammation therapy in a variety of acute and chronic autoimmune diseases (Table 1). This latter approach is based on an early observation thata child with idiopathic thrombocytopenic purpura (ITP) showed an attenuated platelet clearance after IVIG administration, which was conﬁrmed in adult patients shortly thereafter (10, 11). Since then, IVIG administration has been included in the therapy of many chronic autoimmune diseases affecting a wide range of tissues and target organs, such as the skin, joints, central nervous system, and...