Recent Advances in Clinical Glycoproteomics of Immunoglobulins (Igs)

Abstract

Antibody glycosylation analysis has seen methodological progress resulting in new findings with regard to antibody glycan structure and function in recent years. For example, antigen-specific IgG glycosylation analysis is now applicable for clinical samples because of the increased sensitivity of measurements, and this has led to new insights in the relationship between IgG glycosylation and various diseases. Furthermore, many new methods have been developed for the purification and analysis of IgG Fc glycopeptides, notably multiple reaction monitoring for high-throughput quantitative glycosylation analysis. In addition, new protocols for IgG Fab glycosylation analysis were established revealing autoimmune disease-associated changes. Functional analysis has shown that glycosylation of IgA and IgE is involved in transport across the intestinal epithelium and receptor binding, respectively.

Secreted IgM: New tricks for an old molecule

“…29 Due to its large size, ∼970 kDa, pentameric IgM does not easily extravasate into tissues. 31,32 Similar to dimeric IgA, pentameric IgM can bind to the polymeric Ig receptor via its J (joining) chain, which facilitates the transport of IgM across epithelial layers into the lumen of mucosal tissues (see below 33 ). The lamina propria of the human but not the mouse gastrointestinal tract contains significant frequencies of IgM plasma cells.…”

Global variability of the human IgG glycome

“…Predominant allotype variant of IgG3 tryptic peptide carrying N-glycans in Caucasian population has the same amino acid sequence as IgG2. On the other hand, in Asian and African populations predominant variant of the same peptide has the same amino acid composition as IgG4 making the separation of IgG3 from other subclasses impossible using given separation methods 45 . Therefore, IgG glycopeptides were separated into three chromatographic peaks labeled IgG1, IgG2 and IgG4.…”

Global and site‐specific analysis of protein glycosylation in complex biological systems with Mass Spectrometry

“…The applications of glycoproteomics in clinical samples are far more than what we described in this section, there are many comprehensive reviews covering the importance of glycoproteomic technologies in biomedical research (Kim and Varki, ; Tian and Zhang, ; Plomp et al, ; Ruhaak et al, ; Zhang et al, ). Due to the irreplaceable roles of glycoproteins playing in various diseases, high‐throughput glycoproteomic technologies will continue to be developed to enable large‐scale profiling of glycopeptides and glycan structures.…”