Bazedoxifene does not share estrogens effects on IgG sialylation

PLoS One. 2023 May 18;18(5):e0285755. doi: 10.1371/journal.pone.0285755. eCollection 2023.

Abstract

The incidence of rheumatoid arthritis (RA) increases at the same time as menopause when estrogen level decreases. Estrogen treatment is known to reduce the IgG pathogenicity by increasing the sialylation grade on the terminal glycan chain of the Fc domain, inhibiting the binding ability to the Fc gamma receptor. Therefore, treatment with estrogen may be beneficial in pre-RA patients who have autoantibodies and are prone to get an autoimmune disease. However, estrogen treatment is associated with negative side effects, therefore selective estrogen receptor modulators (SERMs) have been developed that have estrogenic protective effects with minimal side effects. In the present study, we investigated the impact of the SERM bazedoxifene on IgG sialylation as well as on total serum protein sialylation. C57BL6 mice were ovariectomized to simulate postmenopausal status, followed by ovalbumin immunization, and then treated with estrogen (estradiol), bazedoxifene, or vehicle. We found that estrogen treatment enhanced IgG levels and had a limited effect on IgG sialylation. Treatment with bazedoxifene increased the sialic acids in plasma cells in a similar manner to E2 but did not reach statistical significance. However, we did not detect any alteration in IgG-sialylation with bazedoxifene treatment. Neither estrogen nor bazedoxifene showed any significant alteration in serum protein sialylation but had a minor effect on mRNA expression of glycosyltransferase in the bone marrow, gonadal fat, and liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Estrogens* / pharmacology
  • Female
  • Immunoglobulin G
  • Mice
  • Mice, Inbred C57BL
  • Selective Estrogen Receptor Modulators* / pharmacology

Substances

  • Estrogens
  • bazedoxifene
  • Selective Estrogen Receptor Modulators
  • Immunoglobulin G

Associated data

  • figshare/10.6084/m9.figshare.22313056

Grants and funding

Swedish Research Council supported salary (CE) and expensive (2019-01852), the Swedish state under the agreement between the Swedish government and the country councils, the ALF agreement supported salary (CE) and expensive (770351 & 965726), Konung Gustav V Foundation supported salary (PG) and expensive, the Swedish Association Against Rheumatism supported salary (PG), OE Edla Johansson Foundation supported expensive and Åke Wiberg Foundation supported salary (CE) and expensive. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.