Immunoglobulin Glycosylation Effects in Allergy and Immunity

Abstract

Both immunoglobulin (Ig) isotype and conserved Fc glycosylation sites often dictate the downstream activity of an Ab where complexity and degree of glycosylation contribute to its ability to bind Fc receptors (FcRs) and activate complement. Most information on the effects of glycosylation center on IgG in cancer therapy and autoimmunity. In cancer therapy, glycosylation modifications that enhance affinity for activating FcRs are utilized to facilitate immune-mediated tumor cell killing. In autoimmunity, disease severity has been linked to alterations in the presence, location, and composition of Fc glycans. Significantly less is understood about the role of glycosylation in the setting of allergy and asthma. However, recent data demonstrate that glycosylation of IgE at the asparagine-394 site of Cε3 is necessary for IgE interaction with the high affinity IgE receptor but, surprisingly, glycosylation has no effect on IgE interaction with its low-affinity lectin receptor, CD23. Variations in the specific glycoform may modulate the interaction of an Ig with its receptors. Significantly more is known about the functional effects of glycosylation of IgG than for other Ig isotypes. Thus, the role of glycosylation is much better understood in the areas of autoimmunity and cancer therapy, where IgG is the dominant isotype, than in the field of allergy, where IgE predominates. Further work is needed to fully understand the role of glycan variation in IgE and other Ig isotypes with regard to the inhibition or mediation of allergic disease.

Maternal IgG impairs the maturation of offspring intrathymic IL‐17‐producing γδT cells: Implications for murine and human allergies

“…Consistent with this proposal, the comparison of IgG subclasses from atopic and non‐atopic individuals did not reveal differences. In addition, we purified serum IgG from patients without any secondary inflammatory disease for which alterations in peripheral IgG glycosylation have been described (eg rheumatoid arthritis or Crohn's disease) . Although these are the main biological differences that may be responsible for the different modulatory potentials of IgG from atopic and non‐atopic individuals, our results suggest that idiotypes can be responsible for IgG effects on human and murine γδT cell maturation.…”

A recurrent missense variant inSLC9A7causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation

“…Glycosylation of proteins and lipids affects numerous cellular processes that are vital for embryonic and postnatal development (93)(94)(95)(96). Hence, it is not unexpected that impaired N-glycan biosynthesis causes or contributes to the progression of various pathophysiological conditions, including cancers, muscular dystrophies, immune dysfunction and neurological disorders (66,84,(97)(98)(99)(100)(101). In the nervous system, polysialylation is essential for normal migration and differentiation of neural precursor cells (102,103), cell-cell and cell-matrix adhesion (104,105) and synapse formation (106).…”

Mass spectrometry for protein sialoglycosylation

“…These modifications enhance the molecular and functional diversity of the proteome to large degree, providing biological access to vast information space at minimum genetic cost . Protein glycosylation is involved in various cellular or molecular mechanisms, including protein folding and stability, molecular functional switching, signaling cascades, enzymatic activity, cancer metastasis, cell adhesion, and cell‐cell interactions . A recent review highlights the multifunctional role of glycosylation in organismal diversity, involving structures, modulation, extrinsic recognition, intrinsic recognition, and molecular mimicry .…”