Association between cognitive impairment and olfactory deficits in systemic lupus erythematosus without major neuropsychiatric syndromes.

OBJECTIVE: The aim of the study was to investigate the utility of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), evaluate cognitive deficits in systemic lupus erythematosus (SLE) patients and examine the relationship between cognitive and olfactory functions. METHODS: 55 SLE patients and 50 healthy controls were administered by RBANS including five indexes: immediate memory (IMME), visuospatial/constructional (Vis/Con), language (LANG), attention (ATT), and delayed memory (DEME). Olfactory functions were evaluated by computerized testing including three stages of smell: threshold (THR), identification (ID), and memory (ME) of different odors. The disease activity and cumulative damage were assessed by the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). RESULTS: SLE patients exhibited significant lower total RBANS scores, IMME, Vis/Con, ATT, and DEME index scores than healthy controls (p < 0.01 for all and p = 0.027 for attention). Reduced RBANS scores were associated with several organ involvement and autoantibodies. SLE patients with higher SLEDAI-2K scores or with accumulated damage (SDI≥1) showed decreased RBANS scores. All the olfactory scores in SLE patients were significantly decreased than controls (p = 0.001). Patients had higher proportion of anosmia (8.57% vs 0%) and hyposmia (28.58% vs 5.72%) than controls (χ2 = 10.533, p = 0.015). Multivariable regression analysis revealed that olfactory functions had a positive effect on RBANS index scores. Olfactory memory and total scores were significantly correlated with the DEME (r = 0.393, p = 0.021) and total scores (r = 0.429, p = 0.011). CONCLUSION: This study indicates that significantly cognitive and olfactory functions are impaired in SLE patients. The RBANS is a potentially useful instrument for evaluating neuropsychological status in SLE. Physicians are encouraged to perform routine screening in SLE patients to detect subtle cognitive dysfunction.

The regulation of the Treg/Th17 balance by mesenchymal stem cells in human systemic lupus erythematosus.

BACKGROUND AND OBJECTIVE: Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) have shown immunoregulation of various immune cells. The aim of this study was to investigate the mechanism of UC MSCs in the regulation of peripheral regulatory T cells (Treg) and T helper 17 (Th17) cells in patients with systemic lupus erythematosus (SLE). METHODS: Thirty patients with active SLE, refractory to conventional therapies, were given UC MSCs infusions. The percentages of peripheral blood CD4+CD25+Foxp3+ regulatory T cells (Treg) and CD3+CD8-IL17A+ Th17 cells and the mean fluorescence intensities (MFI) of Foxp3 and IL-17 were measured at 1 week, 1 month, 3 months, 6 months, and 12 months after MSCs transplantation (MSCT). Serum cytokines, including transforming growth factor beta (TGF-ß), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-17A were detected using ELISA. Peripheral blood mononuclear cells from patients were collected and co-cultured with UC MSCs at ratios of 1:1, 10:1, and 50:1, respectively, for 72 h to detect the proportions of Treg and Th17 cells and the MFIs of Foxp3 and IL-17 were determined by flow cytometry. The cytokines in the supernatant solution were detected using ELISA. Inhibitors targeting TGF-ß, IL-6, indoleamine 2,3-dioxygenase (IDO), and prostaglandin E2 were added to the co-culture system, and the percentages of Treg and Th17 cells were observed. RESULTS: The percentage of peripheral Treg and Foxp3 MFI increased 1 week, 1 month, and 3 months after UC MSCs transplantation, while the Th17 proportion and MFI of IL-17 decreased 3 months, 6 months, and 12 months after the treatment, along with an increase in serum TGF-ß at 1 week, 3 months, and 12 months and a decrease in serum TNF-α beginning at 1 week. There were no alterations in serums IL-6 and IL-17A before or after MSCT. In vitro studies showed that the UC MSCs dose-dependently up-regulated peripheral Treg proportion in SLE patients, which was not depended on cell-cell contact. However, the down-regulation of Th17 cells was not dose-dependently and also not depended on cell-cell contact. Supernatant TGF-ß and IL-6 levels significantly increased, TNF-α significantly decreased, but IL-17A had no change after the co-culture. The addition of anti-TGF-ß antibody significantly abrogated the up-regulation of Treg, and the addition of PGE2 inhibitor significantly abrogated the down-regulation of Th17 cells. Both anti-IL-6 antibody and IDO inhibitor had no effects on Treg and Th17 cells. CONCLUSIONS: UC MSCs up-regulate Treg and down-regulate Th17 cells through the regulation of TGF-ß and PGE2 in lupus patients.