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perspective: Shih-Yao Lin and Jean-Pierre Kinet IMMUNOLOGY: Giving Inhibitory Receptors a Boost Science 2001; 291: 445-446 [Summary] [Full text]

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The Many Faces of IVIG

Jagannadha Avasarala   (14 February 2001)

Fc and F(ab')2 Mediated Effects of IVIG

Hans U. Lutz   (5 February 2001)

The Many Faces of IVIG 14 February 2001
Jagannadha Avasarala, Postdoctoral Fellow Washington University School of Medicine Respond to this E-Letter: Re: The Many Faces of IVIG	The comments made by Lin and Kinet make for interesting reading, but the mechanism of action of intravenous injections of immunoglobulin (IVIG) is perhaps more complex than just its interaction through the FcR gamma inhibitory receptor. The anti-inflammatory actions of IVIG perhaps differ among different diseases. Among the many mechanisms posited, a few include accelerated clearance of endogenous pathogenic auto-antibodies, inhibition of the components of the complement cascade, and neutralization of super-antigens (1). It is also perhaps related to the presence of antibodies in normal human plasma that inhibit the binding of anti-GM1 IgG antibodies as seen in certain neuropathies (2). It is therefore possible that the mechanism or mechanisms of IVIG action are mediated through multiple pathways. References and Notes 1. C. J. Rhoades, Blood Rev. 14(1): 14 (2000). 2. P. H. Lopez, J. Neuroimmunol. 105(2): 179 (2000).
Fc and F(ab')2 Mediated Effects of IVIG 5 February 2001
Hans U. Lutz, Biochemist Inst. Biochemistry, Swiss Federal Institute of Technology, ETH Zurich, Switzerland Respond to this E-Letter: Re: Fc and F(ab')2 Mediated Effects of IVIG	Lin and Kinet discuss a set of interesting results on how intravenous injections of immunoglobulin (IVIG) might down-regulate the clearance of antibody-carrying platelets by macrophages, but they do not present any evidence that this phenomenon has an anti-inflammatory effect. Blockage of the low-affinity inhibitory receptor Fc(gamma)RIIB (FcgRIIB) by a high- affinity antibody evidently abrogated the effect of IVIG, and IVIG was not effective in FcgRIIB-deficient mice. Thus, these receptors appear to be involved. But it is not clear how IVIG or even the Fc portion may recruit these low-affinity receptors. Once exposed on the macrophage surface, down-regulation is mediated by receptor cross-linking, antibody-carrying platelets rather than by IVIG. Several autoimmune diseases effectively treated with IVIG are accompanied by complement activation and systemic inflammation. In such cases, high-dose immunoglobulin G (IgG) has an anti-inflammatory effect that is achieved by down-regulation of complement amplification through stimulation of the physiological inactivation of C3b-C3b-IgG complexes as shown in human sera (1). These complexes are the primary precursor of a C3 convertase and are not only structurally, but also transiently, protected from inactivation by bound properdin (2). This complement-attenuating effect is mediated by F(ab')2 of IVIG (3). References and Notes 1. Blood, vol. 88, 184 (1996). 2. Mol. Immunol., vol. 36, 837 (1999); Biochem J., vol. 349, 217 (2000). 3. Immunopharmacology, vol. 49, 67 (2000).