Objective: The aim of our study was to investigate the efficacy of adipose-derived stem cells (ADSC) transplantation in systemic lupus erythematosus (SLE) and to determine the mechanism of ADSC transplantation. Methods: B6.MRL/lpr mice were administered ADSC intravenously every week from age 28 to 31 weeks, while the lupus control group and the normal control received phosphate buffered solution (PBS) on the same schedule. Results: Compared with the lupus control group, the ADSC treatment group had a significant improvement of histologic abnormalities, serologic abnormalities, and immunologic function. Anti-double-stranded DNA antibodies, spleen/weight ratio, deposits of C3/IgG in the kidney, and serum creatinine and blood urea nitrogen levels were significantly decreased with the transplantation of ADSC. A significant decrease of the Th17/CD4⁺ T cell ratio in the spleen, the serum IL-17 concentration, as well as renal IL-17 expression was observed in the ADSC treatment group. Western blot results also showed that ADSC treatment had a lower expression of protein kinase B (Akt), p-Akt, mTOR, p-mTOR, p70S6K, p-p70S6K, and HIF-1α. Conclusion: ADSC treatment can prevent the development of lupus nephritis and significantly ameliorate already-established disease. ADSC treatment reduced Akt, mTOR, p70S6K, HIF-1α, and that this inhibition can avert IL-17-induced inflammation, suggesting that ADSC may be a promising treatment for SLE.

Objective. Lupus nephritis is the most common and severe complication of systemic lupus erythematosus. The aim of our study was to investigate the efficacy of miR-20a overexpressing adipose-derived stem cell (ADSC) transplantation in murine lupus nephritis (LN) and explore potential molecular mechanisms. Methods. Mouse ADSCs were transfected with a miR-20a lentiviral vector to obtain miR-20a overexpression ADSCs (miR-20a-ADSCs). We first observed the influence of miR-20a on ADSC viability and apoptosis in vitro. B6.MRL/lpr mice were administered ADSC/miR-20a-ADSC intravenously every week from age 30 to 33 weeks, and the lupus and normal control groups received PBS on the same schedule. Results. miR-20a expression increased in miR-20a-ADSC-derived exosomes, and miR-20a overexpression promoted ADSC proliferation and inhibited apoptosis. Compared with ADSCs, miR-20a-ADSC treatment significantly improved serologic and histologic abnormalities, as evidenced by reduced serum creatinine, anti-dsDNA antibody, 24h urine protein levels, nephritis scores, and C3/IgG deposits. Furthermore, miR-20a-ADSC treatment resulted in downregulated Akt, mTOR, and p62 expression and upregulated miR-20a, Beclin 1, and LC3 II/I expression compared with ADSC treatment. After treatment with miR-20a-ADSC, a significant increase in the number of autophagosomes within podocytes was observed, along with upregulated expression of podocin and nephrin, compared with the ADSC group. Conclusions. miR-20a-ADSC transplantation prevents the development of lupus nephritis and significantly ameliorates already-established disease, and its mechanism is related to autophagy by targeting the miR-20a-regulated mTOR pathway.

(2019). Proliferative Sweet syndrome associated with pregnancy and low-molecular-weight heparin sodium. Scandinavian Journal of Rheumatology. Ahead of Print.

Objectives: This retrospective study aims to characterise the epidemiological features of systemic lupus erythematosus (SLE) concomitant with chronic spontaneous urticaria (CSU), examines the correlation between CSU occurrence and lupus disease activity, and identifies comorbidity patterns and risk factors associated with SLE-CSU. Methods: A total of 40 SLE patients with concomitant CSU and 160 age-matched and sex-matched SLE controls without CSU were included. The Mann-Whitney U-test was used to assess disease activity at SLE onset in both groups. A Wilcoxon signed-rank test was conducted to compare the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores before and after CSU onset in patients with SLE. χ ² tests were applied to evaluate differences in SLE activity grading, clinical manifestations, laboratory findings and treatments between patients with SLE with and without CSU. In addition, univariate and multivariate logistic regression analyses were performed to identify risk factors for CSU development in patients with SLE. Results: Wilcoxon signed-rank tests revealed that in the SLE-CSU group, the occurrence of CSU did not result in an increase of SLEDAI scores. Univariate analysis revealed significant differences between the SLE-CSU and SLE-only groups in the presence of cylindruria, elevated IgM, IgA, IgG, serositis, mucosal ulcers and anti-Pm-Scl antibodies (p<0.05). Multivariate logistic regression analysis identified cylindruria (OR: 6.152, CI 2.352 to 16.093, p＜0.001), elevated IgA (OR: 7.598, CI 1.194 to 48.368, p=0.032), elevated IgG (OR: 3.252, CI 1.331 to 7.946, p=0.010) and mucosal ulcers (OR: 3.838, CI 1.166 to 12.637, p=0.027) as independent risk factors for CSU occurrence in patients with SLE. Conclusion: The presence of CSU in patients with SLE does not necessarily indicate increased lupus activity. Rather, cylindruria, mucosal ulcers and elevated IgA and IgG levels were identified as independent risk factors for CSU in patients with SLE.