O-Glycosylation changes in serum IgG3 could be a marker for inflammation development in advanced endometriosis

A group from Division of Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, Poland, etc. has reported that O-Glycosylation changes in serum IgG3 could be a marker for inflammation development in advanced endometriosis.
https://www.mdpi.com/1422-0067/23/15/8087/htm

Structurally, human IgG N-linked glycans are typically biantennary complexes. The second N-glycosylation site is found in the VH and VL (heavy and light chain of variable regions, respectively) and has been observed in 15–25% of all serum IgG. The presence of glycans in the IgG Fab region may contribute to higher antibody stability and modulate antigen binding. For IgG3, apart from N-glycans present in the Fab and Fc regions, the presence of O-linked glycans in the hinge region is also observed.

In blood serum, about 10% of IgG3 polyclonal antibodies and about 13% of IgG3 monoclonal antibodies are considered to contain O-glycans. Each IgG3 molecule can contain up to three O-glycans linked to threonine residues in the triple repeat regions within the hinge region. Although the function of IgG O-glycosylation is still not fully understood, the structure of the hinge region is hypothesized to be able to protect the immunoglobulin from proteolytic cleavage, and may also help maintain the extended conformation and flexibility of IgG3.

In this study, it was examined whether O-glycans are expressed in serum IgG in advanced endometriosis, and also whether, additionally to the presence of biantennary N-glycans, there are also highly branched N-glycans in IgG, and if so, whether the degree of their expression is characteristic of advanced endometriosis.

For the analysis of serum IgG O-glycosylation and the expression of multi-antennary N-glycans, lectin-ELISA with lectins specific to O-glycans (MPL, VVL, and Jacalin) and highly branched N-glycans (PHA-L) was used. And also, isolated serum IgG, i-IgG, and native serum IgG, s-IgG, were examined as samples.

The results were striking. In the case of s-IgG, the clinical value was limited. In the case of i-IgG, however, a maximum high clinical value (AUC = 1) was obtained with all four lectins used, both when comparing women with advanced endometriosis to healthy women and healthy women to a non-endometriosis group.
While this research has shown that both the expression of O-glycans and highly branched N-glycans in IgG may have a potential application in the diagnostics of advanced endometriosis, at the present stage of research, these conclusions mainly concern IgG isolated from serum. This makes it difficult to apply this type of determination in routine diagnostics due to the laborious and time-consuming procedure of protein isolation and purification. Nevertheless, this direction of research seems to be promising, and the development of a simple and fast protein isolation procedure is required.