Role of CD19+ CD5+ CD1d+ Bregs in maintaining the Th17/Treg balance in mice with systemic lupus erythematosus complicated with atherosclerosis.

OBJECTIVE: In this study, we aimed to investigate Bregs, their regulatory effects on Th17/Treg cell balance, and the release of downstream inflammatory factors in a mouse model of low-density lipoprotein receptor (LDLr)-/- + Pristane. METHODS: After the establishment of the mouse model of systemic lupus erythematosus (SLE) complicated with atherosclerosis (AS), 8-week-old LDLr-/- + Pristane mice (n = 10) were included in the SLE + AS group. Furthermore, 8-week-old MRL/lpr and C57 mice were used as the SLE and normal control groups, respectively (n = 10 per group). After feeding the mice a high-fat diet for 14 weeks, peripheral blood and spleen of mice were collected, and Bregs, Th17, and Treg cells and related inflammatory factors were detected by flow cytometry, enzyme-linked immunosorbent assay, and reverse-transcription polymerase chain reaction. RESULTS: The number of Bregs and Tregs in spleen lymphocytes of SLE + AS mice significantly decreased compared with the C57 group (p < .05), whereas the number of Th17 cells significantly increased (p = .000). Furthermore, the proportion of Bregs showed a negative correlation with the Th17/Treg ratio (p = .03). Mice in the SLE + AS group showed higher serum interleukin (IL)-10, IL-17, and tumor necrosis factor-α levels than those in the SLE and C57 groups (p < .05). Furthermore, IL-35 and transforming growth factor (TGF)-ß expression was reduced in the SLE + AS group compared with the C57 group (p < .05). CONCLUSIONS: The proportion of Breg decreases was negatively associated with increased Th17/Treg which was increased in SLE + AS mice, indicating that Bregs may regulate Th17/Treg cell homeostasis and cytokine release via IL-35 and TGF-ß production.

Favorable pregnancy outcomes in two patients with systemic lupus erythematosus treated with belimumab.

BACKGROUND: Systemic lupus erythematosus (SLE) is associated with poor pregnancy outcomes and complications. Belimumab can significantly improve disease activity in patients with SLE. However, there is insufficient evidence to prove the absolute safety of belimumab treatment during pregnancy. CASE SUMMARY: A 37-year-old woman was diagnosed with SLE after a renal puncture biopsy in 2012. The other patient was a 25-year-old woman. She was diagnosed with SLE at 19 years of age. They were treated by standard therapy in the early stage of treatment. The first patient has multiple histories of miscarriages or abortions at different gestational ages caused by SLE activity. The other patient also has persistent thrombocytopenia due to SLE flare. In our patients, SLE was poorly controlled by standard therapy. We initiated belimumab treatment during pregnancy because the benefits of treating SLE outweighed the risks to the fetus. The first patient was admitted to the first belimumab infusion at approximately 14 weeks of gestation. The other patient was admitted to the first belimumab infusion at approximately 12 weeks of gestation. Although our patients did not show complete disease remission during belimumab treatment, neither had serious adverse reactions or adverse pregnancy events, and their babies were in good conditions at birth. CONCLUSION: We present 2 cases of pregnant women with SLE who were treated with belimumab. Both were able to deliver their babies successfully without any complications.