RHEUMATOID ARTHRITIS

Hormone status regulates autoantibody pathogenicity

Credit: S. Harris/Macmillan Publishers Limited

Oestrogen levels can affect the inflammatory properties of autoantibodies by regulating their glycan composition, according to a new study published in Arthritis Research & Therapy. The findings could explain why menopause, which is associated with a decrease in oestrogen, coincides with an increase in susceptibility to rheumatoid arthritis (RA).

Previous work has demonstrated that the composition of glycans present in the Fc region of antibodies (known as IgG-Fc glycans) can regulate antibody effector functions. In particular, a lack of end-terminal sialic acid residues on IgG-Fc glycans increases the pro-inflammatory activity of antibodies, whereas the presence of this residue has anti-inflammatory effects.

To study the link between menopause and antibody responses, Engdahl and colleagues used ovariectomized mice (or sham-operated mice as a control) that were immunized with ovalbumin (OVA). Prior to immunization, the mice were treated with either placebo or oestrogen, modelling the effects of oestrogen deficiency or hormone-replacement therapy (HRT), respectively.

As expected, OVA immunization led to an increase in total and OVA-specific IgG antibody levels. The development and affinity of OVA-specific IgG antibodies was unaffected by oestrogen treatment. However, ovariectomy led to a decrease in OVA-specific IgG antibody sialylation, which was reversed with oestrogen treatment.

“…ovariectomy led to a decrease in OVA-specific IgG antibody sialylation, which was reversed with oestrogen treatment”

Oestrogen induced the expression of the sialylation enzyme β-galactoside α2,6-sialyltransferase 1 (ST6Gal1) in mouse and human plasmablasts. Furthermore, serum antibodies from post-menopausal women with RA receiving HRT had increased levels of sialylation compared with those women with RA not receiving HRT.

These results indicate that oestrogen is a protective factor in RA development, and oestrogen treatment could be beneficial in some patients.

References

Original article

  1. Engdahl, C. et al. Estrogen induces St6gal1 expression and increases IgG sialylation in mice and patients with rheumatoid arthritis: a potential explanation for the increased risk of rheumatoid arthritis in postmenopausal women. Arthritis Res. Ther. https://doi.org/10.1186/s13075-018-1586-z (2018)

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jessica McHugh.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

McHugh, J. Hormone status regulates autoantibody pathogenicity. Nat Rev Rheumatol 14, 385 (2018). https://doi.org/10.1038/s41584-018-0036-2

Download citation