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INTRODUCTION: Existing therapies of systemic lupus erythematosus (SLE) are efficacious only in certain patients. Developing new treatment methods is urgent. This meta-analysis aimed to evaluate the efficacy and safety of low-dose IL-2 (LD-IL-2). METHODS: According to published data from PubMed, Web of Science, Embase, ClinicalTrials.gov, MEDLINE, MEDLINE, Web of Knowledge, Cochrane Library, and FDA.gov, eight trials were included. RESULTS: After the LD-IL-2 treatment, 54.8% of patients had distinct clinical remission. The SRI-4 response rates were 0.819 (95% confidence interval [CI]: 0.745-0.894), and the SELENA-SLEDAI scores were significantly decreased (SMD = -2.109, 95% CI: [-3.271, -0.947], p < .001). Besides, the proportions of CD4+ T (SMD = 0.614, 95% CI: [0.250, 0.979], p = .001) and Treg cells (SMD = 1.096, 95% CI: [0.544, 1.649], p < .001) were increased dramatically after LD-IL-2 treatment, while there were no statistical differences in the proportions of CD8+ T cells, Th1 cells, Th2 cells, and Th17 cells (p > .05). Besides, the proportions of Th17 (SMD = 1.121, 95% CI: [0.709, 1.533], p < .001) and Treg (SMD = 0.655, 95% CI: [0.273, 1.038], p = .001) were significantly increased after receiving subcutaneously 0.5 million IU of LD-IL-2 treatment per day for 5 days, but there were no statistical differences in the proportions of Treg after receiving 1 million IU every other day subcutaneously of LD-IL-2 treatment. Injection site reaction and fever were common side effects of IL-2, which occurred in 33.1% and 14.4% of patients. No serious adverse events were reported. CONCLUSION: LD-IL-2 was promising and well-tolerated in treating SLE, which could promote Treg's proliferation and functional recovery. Injecting 0.5 million IU of IL-2 daily can better induce the differentiation of Treg cells and maintain immune homeostasis than injecting 1 million IU every other day.
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Interleucina-2 , Lupus Eritematoso Sistémico , Humanos , Linfocitos T CD8-positivos , Diferenciación Celular , Interleucina-2/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Subgrupos LinfocitariosRESUMEN
AIM: To investigate the gender and socioeconomic disparities in the global burden of chronic kidney disease (CKD) due to glomerulonephritis from 1990 to 2019. METHODS: Data were extracted from the global burden of diseases (GBD) 2019 study, including incidence, prevalence and disability-adjusted life-years (DALYs). Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in age-standardized rate (ASR) of CKD due to glomerulonephritis. Paired t-test, paired Wilcoxon signed-rank test and Spearman correlation were performed to analyse the association and gender disparity in CKD due to glomerulonephritis. RESULTS: Globally, incident cases of CKD due to glomerulonephritis increased 81% from 9 557 397 in 1990 to 17 308 071 in 2019. The age-standardized incidence rate increased by 1.47 compared with 1990 and DALYs increased by 1.35 compared with 1990 (per 100 000). The number of patients with CKD due to glomerulonephritis in low-middle SDI (3829917) and middle SDI (6268817) regions accounts for more than 55% of the total cases. CKD due to glomerulonephritis caused a higher burden including the incidence rate (p < .0001) and DALY rate (p < .0001) in men compared to women. The age-standardized DALY rate was negatively correlated with SDI (ρ = -0.64, p < .001). In the analysis of risk factors for DALYs, male individuals had a larger burden of hypertension, high BMI and high sodium diet in the DALY rates than female subjects. CONCLUSION: The burden of CKD due to glomerulonephritis was more skewed towards developing and less developed economies and differed by gender, so certain nations should implement far more focused and targeted policies.
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Insuficiencia Renal Crónica , Disparidades Socioeconómicas en Salud , Humanos , Masculino , Femenino , Años de Vida Ajustados por Calidad de Vida , Salud Global , Carga Global de Enfermedades , IncidenciaRESUMEN
BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease. Several proinflammatory cytokines produced by T helper 17 (Th17) cells are involved in the pathogenesis of AS. We performed a meta-analysis to determine the levels of Th17 cells and serum Th17-associated cytokines in patients with AS. METHODS: We determined the levels of Th17 cells and Th17 cytokines in patients with AS using data extracted from published articles retrieved from the PubMed, Embase, Web of Science, Cochrane Library, MEDLINE, Web of Knowledge, Clinical Trials.gov, and FDA.gov. DATABASES: The effect estimates were pooled using a random-effects model. The review protocols were registered on PROSPERO (reference: CRD42021255741) and followed the PRISMA guideline. RESULTS: This meta-analysis included 138 studies. Compared to healthy controls (HCs), patients with AS had a higher proportion of Th17 cells (standardized mean difference [SMD] 2.23, 95% confidence interval [CI] 1.78-2.68; p < 0.001) and levels of proinflammatory cytokines, such as interleukin (IL)-17 (SMD 2.04, 95% CI 1.70-2.38; p < 0.001), IL-21 (SMD 1.77, 95% CI 0.95-2.59; p < 0.001), and IL-23 (SMD 1.11, 95% CI 0.78-1.44; p < 0.001). The subgroup analysis showed higher levels of IL-17+ Th17 cells among peripheral blood mononuclear cells (PBMCs) and CD4+ T cells in patients with AS compared to HCs (SMD 2.26, 95% CI 1.58-2.94 [p < 0.001] and SMD 1.61, 95% CI 0.55-2.67 [p = 0.003], respectively). Patients with AS had higher levels of CD4+IL-17+IFN-γ- Th17 in PBMCs and of CD4+CCR6+CCR4+Th17 in CD4+ T cells compared to HCs (SMD 1.85, 95% CI 1.06-2.64 [p < 0.001] and SMD 7.72, 95% CI 6.55-8.89 [p < 0.001], respectively). No significant differences were observed in the proportions of CD4+IL-17+IFN-γ- Th17 in CD4+ T cells and CD4+CCR6+CCR4+ Th17 in PBMCs (SMD - 0.11, 95% CI - 0.61 to 0.38 [p = 0.650] and SMD 1.32, 95% CI - 0.54 to 3.19 [p = 0.165], respectively). In addition, compared to stable AS, the levels of Th17 cells and IL-17 and IL-23 were significantly higher in active AS (SMD 1.58, 95% CI 0.30-2.85 [p = 0.016], SMD 3.52, 95% CI 0.72-6.33 [p = 0.014], and SMD 5.10, 95% CI 1.83-8.36 [p = 0.002], respectively). CONCLUSIONS: The levels of Th17 cells and serum IL-17, IL-21, and IL-23 were higher in patients with AS than in HCs and, compared with stable AS, they increased more significantly in active AS. These results suggest that Th17 cells and Th17-related cytokines play major roles in AS pathogenesis and are an important target for treatment.