IntroductionThe balance between T helper 17 (Th17) and regulatory T cells (Treg) is a new paradigm in the pathogenesis of systemic lupus erythematosus (SLE). Currently, there are no drugs that able to modulate Th17/Treg balance specifically in SLE. Curcumin is a bioactive agent that has a specific action against hyperproliferative cells. However, its role in modulating Th17/Treg balance in SLE is still unknown. This research aimed to investigate the role of curcumin in modulating Th17/Treg balance on CD4+ T cell cultures of SLE patients.Material and methodsCD4+ T cells from SLE 6 untreated patients and 6 healthy subjects were collected, stimulated with Th17 differentiating factors, and curcumin 0.1 and 1 µg/ml was added on cultures. After 72 hours incubation, cells were harvested and measured for Th17 and Treg percentages using flow cytometry and interleukin-17A (IL-17A) and transforming growth factor-β1 (TGF-β1) levels using ELISA.ResultsAdministration of low doses of curcumin (0.1 and 1 µg/ml) could decrease Th17 percentages (p = 0.000 and p = 0.000 compared to control), reduce IL-17A productions (p = 0.000 and p = 0.000 compared to control), increase Treg percentages (p = 0.001 and p = 0.000 compared to control), and increase TGF-β1 productions (p = 0.001 and p = 0.000 compared to control) on CD4+ T cells of SLE patients. Interestingly, these effects were not reproduced on CD4+ T cells cultures of healthy subjects.ConclusionsThese data suggest that curcumin can modulate Th17/Treg balance specifically on CD4+ T cells of SLE patients without affecting healthy subjects.

The aim of this study was to determine the role of vitamin A in modulating T helper 17 (Th17) and regulatory T cell (Treg) balance in systemic lupus erythematosus (SLE) patients. Sixty-two female SLE patients and sixty-two female controls were measured for vitamin A levels from serum by enzyme-linked immunosorbent assay (ELISA) and percentages of Th17 and Treg from peripheral blood mononuclear cells (PBMC) by flow cytometry. We also performed an in vitro study to evaluate the effects of retinoic acid treatment (0, 0.1, 0.2, and 0.3 μg/ml) in modulating Th17/Treg balance in CD4(+) T cell culture from hypovitaminosis A SLE patients. Th17 and Treg percentages from cell cultures were measured by flow cytometry. Vitamin A levels in the SLE patients were lower compared to those in the healthy control (46.9 ± 43.4 vs. 75.6 ± 73.1 ng/ml, p = 0.015). Vitamin A levels also had a negative correlation to Th17 percentages in the SLE patients (p = 0.000, R = -0.642). Th17 percentages in the hypovitaminosis A SLE patients were higher compared to those SLE patients with normal vitamin A levels (10.9 ± 5.3 vs. 2.9 ± 2.2 %, p = 0.000). Treatment of 0.3 μg/ml of retinoic acid could increase Treg differentiation (33.9 ± 1.6 vs. 21.8 ± 1.1 %, p = 0.000) and decrease Th17 differentiation (27.2 ± 2.5 vs. 37.4 ± 1.3 %, p = 0.000). In conclusion, vitamin A has important roles in modulating Th17/Treg balance in the SLE patients shown by the significant decrease of vitamin A levels in the SLE patients which negatively correlate with Th17 population, and treatment of retinoic acid could decrease Th17 and increase Treg percentages in CD4(+) T cells cultures.

Aims: Cognitive impairment is common in systemic lupus erythematosus (SLE) patients with substantial adverse effects on function and quality of life. One hypothesis to understand the mechanisms of cognitive impairment in SLE is accelerated immunosenescence. The aim of this study is to observe the correlation between immunosenescence with cognitive impairment in patients with SLE. Methods: Sixty-one female SLE patient were measured for CD4 and CD8 T cellassociated senescence markers, including percentage of end-stage differentiated T cells (CD4 and CD8 T cells expressing CD57 + or loss of CD28 expression), of naïve T cells (CD4 + CD45RA + and CD8 + CD45RA + ), memory T cells (CD4 + CD45RO + and CD8 + CD45RO + ), and antigen-experienced T cells (CD4 + KLRG1 + and CD8 + KLRG1 + ) which were measured using flow cytometry. One hallmark of immunosenescence called immune risk profile (IRP) was defined by an inverted ratio of CD4 and CD8. Cognitive functions were measured by Mini-Mental State Examination (MMSE) and Montréal Cognitive Assessment (MOCA) questionnaire. Results: Thirty-six (59.1%) SLE patients who had IRP develop significantly lower attention and recall from both MMSE (P = .005 and P = .000) and MOCA (P = .017 and P = .000) examinations. Decreased visuospatial ability was also found in patients with IRP measured by MOCA (P = .046). There was a negative correlation between memory CD4 + CD45RO + T cells with recall and visuospatial domain (R = −0.204, P = .039 and R = −0.250, P = .033; respectively), and negative correlation between CD8 + CD28 -T cells with recall and attention domain (R = −0.249, P = .027 and R = −0.145, P = .048, respectively). Conclusion: Systemic lupus erythematosus patients develop an accelerated immunosenescence which contributes to cognitive dysfunction, especially in attention, recall, and visuospatial domains. K E Y W O R D S immunosenescence, lupus-associated brain fog, systemic lupus erythematosus | 621 KALIM et AL.

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Objectives: This study aims to investigate the relationship between systemic lupus erythematosus and pregnancy in pristane induced lupus mice model, including the pregnancy outcome for mothers and neonates. Materials and methods: Sixteen female Balb/c mice 6-8 week-old were separated into two groups: pristane induced lupus (PIL) mice group that received a single intraperitoneal injection of 0.5 ml of pristane and healthy control (HC) group that received phosphate-buffered saline injection. At one month after injection, all mice were mated with 8-10 week-old male Balb/c mice. All mice from both groups were observed for body weight and survival. On the day of births; number of neonates born, birth weight, and length of neonates were calculated. Neonates were also monitored for survival rate and their ages along the study. Results: There was no statistically significant difference in body weight before and after delivery, survival rate during pregnancy, number of neonates born, and gestational ages of mothers from both groups. Mothers began to die in the postpartum period. On third day after delivery, 0% of mothers from PIL group survived whereas 100% mothers from HC group survived (p=0.000). Of neonates born from PIL group, 15% survived at the end of fifth day after birth whereas 100% of neonates from HC group still survived (p=0.000). Neonates from PIL group also had significantly lower body weight and body length at birth compared to HC group (p=0.000 and p=0.000, respectively). Conclusion: Maternal and neonatal death, low birth weight, and low birth length are complications of systemic lupus erythematosus at pregnancy in pristane induced lupus mice model.

Active immunization with IL-17A coupled to KLH was able to induce a high titer of neutralizing antibodies against IL-17A and inhibit B cell functions without increasing the risk of infection in a pristane-induced lupus mice model.

IntroductionSystemic lupus erythematosus (SLE) patients are predisposed to chronic immune activation, leading to accelerated immunosenescence. The aging of the immune system causes the T cells to express several senescence markers such as CD57 and KLRG1, which produce pro-inflammatory cytokine interferon  (IFN-). Immunosenescence was associated with high morbidity and mortality in other diseases. This research was conducted to prove the association between senescent T cells and SLE disease activity.Material and methodsThis research was an observational cross-sectional study on 53 women aged 16–45 years diagnosed with SLE based on SLICC 2012 criteria. All subjects were recorded for demographic and clinical data, and their SLE disease activity index (SLEDAI) score was measured to evaluate disease activity. Active disease was defined as SLEDAI score ≥ 3. The CD57 antigen and KLRG1 expression on CD4+ and CD8+ T cells were calculated from peripheral blood mononuclear cells (PBMC) by flow cytometry. Interferon  was measured from serum using ELISA. The comparison was done using the Mann-Whitney test, and correlation was tested using the Spearman test. Associations between variables were calculated using linear regression models.ResultsSystemic lupus erythematosus patients with active disease had markedly higher CD4+KLRG1+ (3.1 [1.3–5.5]% vs. (0.3 [0.1–0.5]%), CD8+CD57+ (11.6 ±7.1% vs. 2.4 ±2.0%, p = 0.000), and CD8+KLRG1+ T cell percentages (13.7 ±7.5% vs. 0.3 ±0.1%, p = 0.000), and IFN- levels (208.9 [148.3–233.8] vs. 146.7 [130.2–210.8] pg/ml, p = 0.048), compared to the inactive patients. Positive correlation and association was found between the CD8+CD57+ and CD8+KLRG1+ percentages with the SLEDAI score (p = 0.007 and p = 0.007, for the linear regression analysis, respectively).ConclusionsSystemic lupus erythematosus patients showed significantly higher senescence T cell markers compared to controls, and the increase of T cell senescence, especially in the CD8 compartment, has some association with increased disease activity in patients with SLE.