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'Does He Take Sugar?' is a long running BBC radio programme describing the plight of the handicapped who are ignored frequently and whose worth is often doubted. By analogy in the study of immunoglobulins, and many other proteins, scant attention has been given to the oligosaccharides that are actually an integral part of them. Glycosylation of proteins is widespread in eukaryotes, yet practically absent in prokaryotes. This is perhaps unsurprising in view of the fact that the major function of glycoprotein molecules lies in recognition of intercellular signals. Such recognition can involve membrane bound proteins on cell surfaces-for example the selectins, which mediate the attachment of leucocytes to endothelial cells, permitting their extravasation.' The oligosaccharide binding domains of these molecules are homologous and essential for their function. Alternatively, glycoprotein signals may operate over long distances. The gonadotrophins and thyroid stimulating hormone are all glycoproteins. If these hormones are deglycosylated, biological activity is reduced and clearance rate increased.2 In the immune system, major histocompatibility complex antigens, T cell receptors, and immunoglobulins have all been shown to be glycosylated.3 ' Some divalent antibodies become monovalent after glycosylation, as a result of blockage of one of the antigen binding sites by oligosaccharide.5 Effector functions are influenced by Fc linked oligosaccharide. Thus binding to macrophage Fc receptor and complement C 1q in vitro are reduced when sugars are enzymatically removed from IgG molecules.6 The increasing interest in the subject of glycoimmunology is reflected in the three meetings on the subject that have taken place in the past six years. The introduction of the journals Glycobiology and Glycosylation and Disease also reflects the greater awareness of glycosylation research. It is 10 years since the first detailed analysis of the variation in oligosaccharide structures attached to serum IgG was published.7 Human IgG is mainly glycosylated with N-linked carbohydrates, and glycosylation of the Fc region occurs at asparagine 297, on which two opposing biantennary arms of oligosaccharide protrude and interact. Figure 1 depicts a space filling model of this arrangement. The study, published in 1985, followed an earlier, much smaller study8 and showed that serum IgG from patients with rheumatoid arthritis (RA) and, to a lesser extent, osteoarthritis had an increased number of oligosaccharide structures in which the outer arms lacked galactose and terminated in N-acetyl glucosamine (GlcNAc). These agalactosyl oligosaccharides was generally referred to as Gal(O). With hindsight it was easy to see that an important difference between those patients with RA and osteoarthritis reported to have increased Gal(O) was the older age of those with osteoarthritis. In a subsequent study9 of 151 normal healthy individuals (both men and women) varying in age from one to 70 years, it was demonstrated that the relative incidence of agalactosyl IgG was indeed age dependent. It has now been established that at birth most IgG is fully glycosylated, though during the first year of life about 50% of the IgG produced is agalactosylated. From one to approximately 15 years of age, the proportion decreases to around 15-20%; it remains virtually constant up to the age of 40, but then increases steadily. These observations have been confirmed using both a complex biochemical method and a lectin binding assay.'0 This latter assay takes advantage of the fact that different lectins bind selectively to different sugars. This method also offers

Does it take sugar? A clinical role for measuring the glycosylation of IgG?