Nature Highlights . . . Antibody salivary acid modification affects allergic reactions.

In this paper, the binding of XueYue IgE antibody with FC ε RI on the surface of mast cells and basophils leads to cell activation and release of histamine, prostaglandin and leukotriene.this cascade reaction can lead to allergic diseases, the most serious of which is anaphylaxis.at present, it is considered that IgE is absolutely necessary to trigger the cascade reaction, but some studies have found that the concentration of IgE is not always correlated with allergic diseases [1].studies have shown that glycosylation of IgG can determine molecular function and has disease specificity [2]. However, whether the glycosylation of IgE can affect its biological activity and determine the disease status is still unknown. There are seven N-glycosylation sites in the heavy chain of human IgE.IgE is the lowest antibody category in the circulation. The analysis of Hige glycosylation is limited to the samples of myeloma, high IgE syndrome, high immune syndrome or recombinant IgE.studies showed that there was only one n-mannooligosaccharide at n394 of IgE, n383 was not occupied, and the other five sites were occupied by complex antenna glycan [3].previous studies have revealed that Oligomannose at n394 is required for the correct folding and binding of IgE to FC ε RI.on May 20, 2020, the Robert M. Anthony team from Harvard Medical School published an article entitled sialylation of immunoglobin e is a determining of allelic pathogenicity in nature.this study found that sialylation of IgE in peanut allergic reaction distinguished allergic IgE from non allergic IgE.first of all, the author selected the research samples and compared the IgE concentrations of those who had no allergy history, peanut allergy, pollen allergy, dust mite allergy and cat allergy at the onset of allergic reaction. It was found that the IgE titer of peanut allergy patients was significantly higher than that of other allergens.however, after enrichment and separation of mast cells from those samples with similar IgE titers and those with peanut allergy, it was found that although the IgE load was similar, mast cells in peanut allergy patients were more degranulated, which indirectly indicated that there were differences in the intrinsic function of IgE, rather than the difference in titer.the authors used mass spectrometry to analyze the N-glycan modification of IgE in these samples, and finally found that sialylation of allergic IgE increased specifically.galactose modified N140 and n265 are rich in non-specific IgE, while n168 and n265 of allergic IgE are rich in terminal sialic acid modification, especially bisialylated glycan, which can distinguish allergic and non allergic IgE.next, the authors used the passive cutaneous anaphylaxis (PCA) model to verify the above findings.sensitized mice were injected with PBS, ova sialylated IgE and ova desialylated IgE into ear endothelium respectively.If sialic IgE is reconnected to sialic acid, the sensitization ability will be restored.using the system sensitization model, the same conclusion has been obtained. PCA results: PBS control group; siamoge sialic IgE; asmige sialic acid removed IgE; re siamoge siamic acid reconnected IgE. after further investigation, the authors found that desialylation did not affect the binding ability of IgE to allergens, mast cells and FC ε RI. the downstream signal activation of FC ε RI was detected, and the downstream signal was inhibited by the desialylation of IgE. although it can still bind to the receptor and occupy the receptor binding position, IgE after sialylation is converted into inhibitory glycoprotein. due to the above phenomenon, the author considered whether sialic acid could be targeted to alleviate allergic reaction. the fusion protein neufc ε (neuraminidase neu is used to remove sialic acid and fuse with IgE FC C ε 2-4 domain) was prepared to remove sialic acid modification of IgE. in vivo and in vitro experiments confirmed that the fusion protein neufc ε could significantly reduce the level of allergic reaction. this study found that sialic acid modification of IgE in peanut allergy is essential for activating downstream signals of receptors. allergic reactions can be alleviated by removing sialic acid from IgE or by treating with desialylated glycoprotein. although the role of sialylation of IgE in other conditions is not clear, this paper reveals that sialylation is an important factor in regulating biological function. sialic IgE provides a more effective diagnosis and treatment strategy. Du toit, G. et al. Random trial of peanut consumption in funds at risk for peanut energy. N. Engl. J. Med. 372, 803 – 813 (2015). 2, Arnold, J. n., WORMALD, M. R., SIM, R. B., Rudd, p. m. & amp; dwek, R. A. The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu. Rev. Immunol. 25, 21–50 (2007).3, Plomp, R. et al. Site-specific N-glycosylation analysis of human immunoglobulin E. J. Proteome Res. 13, 536–546 (2014)