Intravenous and subcutaneous immunoglobulin (IVIg/SCIg) preparations, containing pooled immunoglobulin (Ig)G antibodies from thousands of healthy donors, have a wide range of clinical applications and have been in use for more than 50 years 1. The two main clinical indications for which IVIg/SCIg are used are IgG replacement in primary immunodeficiencies and anti-inflammatory therapy in a variety of autoimmune and allergic diseases. Despite a broad range of uses, the exact mechanisms of the immunoregulatory effects of IVIg are still unclear 2,3. An overall better understanding of the mechanisms of action of IVIg/SCIg is crucial to guide more rational use of these drugs.
It has been demonstrated that IVIg can bind to sialic acid-binding immunoglobulin-type lectins (Siglecs) 4–6, which are an inhibitory receptor family expressed on the surface of immune cells. The primary function of Siglecs is to bind glycans (carbohydrate structures) containing sialic acids. Glycans and glycan–protein interactions are responsible for ABO blood group determination and numerous processes in the body, including molecular mimicry, cellular adhesion and tumour immunosurveillance. A recent study by Jandus et al. 7 has shown that tumour cells that exhibit aberrant glycosylation and engage inhibitory Siglec receptors on natural killer cells can escape surveillance by innate immunity. Glycan–protein interactions are also important in host–pathogen interactions. In colonizing a host, the process of adhesion is often mediated by lectins present on the surface of the pathogen that interact with complementary carbohydrates on the host cells 8. Glycan-mediated adhesion has been demonstrated for bacteria, bacterial toxins and viruses 9. Given the multifaceted roles of protein-glycan interactions in autoimmunity, infection and cancer, it is therefore of particular interest to understand the binding capacity of antibodies to glycan structures.
Healthy individuals exhibit a broad range of anti-carbohydrate IgG antibodies to specific biologically relevant glycans 10, or to their receptors, that might contribute to the beneficial clinical effects witnessed with IVIg/SCIg therapy.
Acknowledgments
Research by the author is supported by grant number GM62116 to the Consortium for Functional Glycomics; the Bulgarian-Swiss Research Program (BSRP) no. IZEBZ0_142967; the CSL Behring Research Scholarship Award (RS 01/2009); and the Swiss National Science Foundation (SNSF) grant no. 310030_135734 to S. von Gunten. S. v. G. would like to thank Meridian HealthComms Ltd for providing medical writing services.
Disclosures
S. v. G. has no conflicts of interest.
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