Treatment with a tissue-selective oestrogen complex does not affect disease pathology but reduces pre-BI cells in lupus-prone mice

Abstract

Objective

Systemic lupus erythematosus (SLE or lupus) is an autoimmune disease characterized by B-cell dysfunction, production of autoantibodies, and immune complex formation. Lupus is overrepresented in females, indicating that sex hormones play a role in the pathophysiology. Treatment with a tissue-selective oestrogen complex (TSEC) containing conjugated oestrogens and the selective oestrogen receptor modulator bazedoxifene (BZA) protects against postmenopausal vasomotor symptoms and osteoporosis, but its impact on organ damage in lupus is not fully understood.

Method

We used ovariectomized MRL/lpr mice, treated with two different physiological doses of 17β-oestradiol-3-benzoate (E2), BZA, or TSEC (E2 plus BZA), to assess early and late B-cell development and to determine histological disease manifestations in the kidneys and salivary glands.

Results

TSEC treatment reduced the frequency of the pre-BI population in bone marrow to levels equivalent to treatment with physiological doses of E2 alone but did not affect any of the other examined B-cell populations. Our earlier studies indicated that TSEC treatment did not aggravate disease development in ovariectomized MRL/lpr mice, while protecting against trabecular bone loss. Here, we follow up on our previous study and show that neither ovariectomy alone nor TSEC treatment of ovariectomized MRL/lpr mice influenced perivascular lymphocyte infiltration to the kidneys or salivary glands.

Conclusion

TSEC does not aggravate a mouse model of lupus, when given in doses that protect against postmenopausal lupus-associated bone loss. This indicates that further investigations into TSEC as a treatment for osteoporosis or vasomotor symptoms in postmenopausal women with SLE are warranted.

Acknowledgements

We thank Alicia Maria del Carpio Pons for excellent technical assistance. Figure 4 was created using BioRender software.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethics approval

All work was approved by the animal ethical review board in Gothenburg (ethical permit number: 95-2015).

Data availability statement

The data supporting the conclusions of this study are available within the article.

Authors’ contributions

CD, JN, HC, and UI planned the experiments; CD, JMS, JN, and CE performed the experiments. CD, JMS, HC, and UI analysed and interpreted the results of the experiments. CD, HC, and UI drafted the manuscript. CD, JMS, JN, CE, HC, and UI edited the manuscript. All authors approved the final version of the manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/03009742.2023.2251753

Additional information

Funding

This work was supported by the Swedish Research Council [2016-01192 and 2020-0185], the Novo Nordisk Foundation [19928, ALFGBG- 716421, ALFGBG-965238, ALFGBG-857161, and ALFGBG-770351], the Association Against Rheumatism [R-931683, R-9400384], King Gustaf V’s 80 Years’ Foundation [FAI-2019-0573, and FAI-2020-0647], the Wilhelm and Martina Lundgren Science Foundation, the Professor Nanna Svartz Foundation [Stiftelsen Professor Nanna Svartz Fond. 2019-00281 and 2020-00338], the Emil and Wera Cornell Foundation, and the IngaBritt and Arne Lundberg Foundation [LU2018-0008 and LU2020-0010]. The funding sources had no role in the study.