The current study was to determine the predictors of survival in 491 Chinese patients with lupus nephritis (LN). All patients were evaluated and consecutively followed up from 2003 to 2010. The female: male ratio was 9.5:1, with a median age of 31.1 ± 12 years. Forty-nine (10.0%) patients were lost to follow-up and 47 (10.3%) patients died. The overall cumulative probability of survival at 5, 10, 15 and 20 years by Kaplan-Meier analysis was 88%, 77%, 53% and 45%, respectively. The log-rank test showed that the probability of survival was significantly decreased in the late-onset patients (≥50 years) (P = 0.036), patients with hypoproteinaemia (≤35 g/l) (P = 0.014), patients with increased creatinine (≥1.5 mg/dl) (P = 0.002) and patients with massive proteinuria (≥3.5 g/24 h) (P = 0.009). However, the probability of survival was significantly higher in patients treated with hydroxychloroquine (HCQ) (P = 0.003) than those not treated with it. Based on a multivariate model, increased creatinine (hazard ratio (HR) = 2.041; P = 0.017) and proteinuria ≥3.5 g/24hours (HR=1.716; P = 0.016) were independent risk factors. Glucocorticoid (HR = 0.457; P = 0.01) and HCQ (HR=0.197; P = 0.026) were independent protective factors. Our findings suggest that renal dysfunction and massive proteinuria are independent risk factors for mortality. HCQ could improve the survival of patients with LN.

Interferon-γ (IFN-γ), a pleiotropic lymphokine, has important regulatory effects on many cell types. Although IFN-γ is essential for the initiation of uterine vascular modifications and maintenance of decidual integrity, IFN-γ administration can also cause pregnancy failure in many species. However, little is known about the effector mechanisms involved. In this study, using an IFN-γ-induced abortion mouse model, we reported that no Dolichos biflorus agglutinin lectin-positive uterine natural killer (uNK) cells were observed in the uteri from IFN-γ-induced abortion mice. By contrast, the percentage of CD3−CD49b+ NK cells in the uterus and blood from a foetal resorption group was significantly higher than that of the control group. Similarly, significantly upregulated expression of CD49b (a pan-NK cell marker), CX3CL1 and CX3CR1 (CX3CL1 receptor) was detected in the uteri of IFN-γ-induced abortion mice. Using isolated uterine stromal cells, we showed that upregulated expression of CX3CL1 by IFN-γ was dependent on a Janus family kinase 2-signal transducers and activators of transcription 1 (JAK2-STAT1) pathway. We further demonstrated the chemotactic activity of CX3CL1 in uterine stromal cell conditioned medium on primary splenic NK cells. Finally, we observed increased recruitment of CD49b+ NK cells into the endometrium after exogenous CX3CL1 administration. Collectively, our findings indicate that IFN-γ can significantly increase uterine CX3CL1 expression via activation of the JAK2-STAT1 pathway, thus inducing CD49b+ NK cell uterine homing, and eventually provoke foetal loss. Thus, we provide a new line of evidence correlating the deleterious effects of IFN-γ on pregnancy with the aberrant regulation of CX3CL1 and CD49b+ NK cells.

No abstract