Interferon λ3

干扰素 λ 3
  • 文章类型: Journal Article
    BACKGROUND: The clinical course of hemodialysis patients with COVID-19 still remains unclear.
    METHODS: Thirty-four hemodialysis patients were retrospectively enrolled. Patients were divided according to disease severity, and clinical symptoms and laboratory data at admission were compared.
    RESULTS: The serum C-reactive protein (CRP) level, D-dimer level, and white blood cell (WBC) count were significantly higher in the group with critical disease than in the group with mild to severe disease (P = 0.005, P = 0.039 and P = 0.045). The serum CRP level exceeded 10 mg/dL within 7 days of clinical onset in all the cases with critical disease.
    CONCLUSIONS: Hemodialysis patients with COVID-19 who have elevated serum CRP and D-dimer levels, and an elevated WBC count at admission and patients with serum CRP levels exceeding 10 mg/dL before day 7 after clinical onset should be carefully monitored for possible progression to critical disease. This article is protected by copyright. All rights reserved.
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  • 文章类型: Clinical Trial
    IFNL4多态性与循环IFN-λ3相关,较高的血浆IFN-λ3与HBV表面抗原(抗HBs)抗体的较高产量相关。响应HBV疫苗的IFNL4rs8099917T等位基因和抗HBs开发与血液透析(HD)患者的更好生存率相关。
    显示血浆IFN-λ3是否也是HD患者存活的预测因子。
    在135例HD患者中测量血浆IFN-λ3,随访2.6年。使用Kaplan-Meier方法和Cox比例风险模型测试生存概率。
    HD幸存者的血浆IFN-λ3(ng/L)为116.8(20.4-227.5)(n=89,65.9%),死亡患者75.1(36.0-228.8)(n=37,27.4%),接受肾脏移植的受试者(n=9,6.7%)和109.0(40.0-232.7)。死亡患者的IFN-λ3低于所有其余患者(P=0.039)和未进行移植的HD患者(P=0.028)。IFN-λ3和抗-HBs滴度相关(r=0.587,P<0.000001)。显示IFN-λ3>126.1ng/L(第三三分)的患者与第1位的IFN-λ3患者相比,生存率更高(<73.8ng/L,P=0.005)和第二(≥73.8-<126.1ng/L,P=0.013)三元率。每10ng/LIFN-λ3的减少与等于1.076的风险比相关(95CI1.015-1.140,P=0.013)。在多变量分析中,生存的独立预测因素是年龄(P=0.008),透析方式(P=0.038),循环IFN-λ3(P=0.044),糖尿病肾病(P=0.047),但不是性别,研究前的透析持续时间,平均动脉压,BMI,CRP,白蛋白,25(OH)D,或抗HBs。
    循环IFN-λ3是HD患者生存的有希望的预测因子。
    IFNL4 polymorphisms are associated with circulating IFN-λ3, and higher plasma IFN-λ3 are associated with higher production of antibodies to HBV surface antigen (anti-HBs). The IFNL4 rs8099917 T allele and anti-HBs development in response to HBV vaccine are associated with better survival in hemodialysis (HD) patients.
    To show whether plasma IFN-λ3 is also a predictor of survival in HD patients.
    Plasma IFN-λ3 was measured in 135 HD patients who were followed-up for 2.6 years. Survival probability was tested using the Kaplan-Meier method and the Cox proportional hazard model.
    Plasma IFN-λ3 (ng/L) was 116.8 (20.4-227.5) in survivors on HD (n=89, 65.9%), 75.1 (36.0-228.8) in deceased patients (n=37, 27.4%), and 109.0 (40.0-232.7) in subjects submitted to kidney transplantation (n=9, 6.7%). IFN-λ3 was lower in deceased patients than that in all remaining patients (P=0.039) and patients who continued HD without transplantation (P=0.028). IFN-λ3 and anti-HBs titers were correlated (r=0.587, P<0.000001). Patients showing IFN-λ3 >126.1 ng/L (3rd tertile) presented better survival compared with patients with IFN-λ3 in the 1st (<73.8 ng/L, P=0.005) and 2nd (≥73.8 - <126.1 ng/L, P=0.013) tertiles. Each decrease in IFN-λ3 per 10 ng/L was associated with a hazard ratio equal to 1.076 (95%CI 1.015-1.140, P=0.013). In multivariate analysis, the independent predictors of survival were age (P=0.008), dialysis modality (P=0.038), circulating IFN-λ3 (P=0.044), and diabetic nephropathy (P=0.047), but not gender, dialysis duration prior to the study, mean arterial pressure, BMI, CRP, albumin, 25(OH)D, or anti-HBs.
    Circulating IFN-λ3 is a promising predictor of HD patient survival.
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  • 文章类型: Journal Article
    干扰素λ-3(IFNλ3)(也称为IL28B)是III型干扰素的成员,其在结构上和遗传上不同于I型干扰素。这些干扰素诱导类似于I型干扰素的信号转导途径,其导致干扰素刺激基因(ISG)的激活。这组干扰素是组织特异性的,据报道具有抗病毒活性。在目前的通信中,我们报道了牛IFNλ3基因(编码成熟蛋白)在毕赤酵母中的表达,纯化表达的蛋白质并评价其生物活性。转化的毕赤酵母细胞表达约19kDa蛋白,分泌到培养基中,通过SP-Sepharose离子交换色谱用NaCl逐步梯度洗脱纯化蛋白质。蛋白质的特异性通过Western印迹证实。发现表达IFNλ3的毕赤酵母具有生物活性,当它诱导ISGs(Mx蛋白,牛PBMC中的OAS和PKR基因)。此外,还发现其调节受刺激的牛PBMC中的Th1/Th2细胞因子表达。
    Interferon lambda-3 (IFNλ3) which is also known as IL28B is a member of type III Interferons which are structurally and genetically different from type I Interferons. These Interferons induce signal transduction pathways similar to type I Interferons which results in the activation of Interferon Stimulated Genes (ISGs). This group of Interferons are tissue specific and reported to have antiviral activity. In the present communication, we report the expression of bovine IFNλ3 gene (coding for the mature protein) in Pichia pastoris, purification of the expressed protein and evaluation of its biological activity. About 19 kDa protein expressed by the transformed Pichia cells, secreted into the media and the protein was purified by SP-Sepharose ion exchange chromatography with NaCl stepwise gradient elution. Specificity of the protein was confirmed by Western blotting. Pichia expressed IFNλ3 was found to be biologically active, as it induced ISGs (Mx protein, OAS and PKR genes) in bovine PBMCs. Further it was also found to modulate Th1/Th2 cytokines expression in the stimulated bovine PBMCs.
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  • 文章类型: Journal Article
    背景:循环促炎细胞因子与相对死亡风险增加相关,而反映T细胞功能改善的免疫参数是血液透析(HD)患者生存的预测因子。我们在前瞻性研究中评估了T辅助细胞细胞因子相关基因的变异是否是HD患者死亡率的决定因素。
    方法:这项研究是在532名流行HD受试者中进行的,他们随访了7年。HRM分析用于IFNL3、IL12A、IL13和IL4R基因分型。CCL2,IL12B,使用PCR-RFLP分析对IL18进行基因分型。使用Kaplan-Meier方法和Cox比例风险模型进行生存分析。
    结果:在单变量分析中,在隐性遗传模型中,IFNL3rs8099917与全因死亡率相关(对数秩检验P=0.044),IL12Ars568408-在显性模型中(对数秩检验P=0.029)。IFNL3rs8099917中的次要纯合子(基因型GG)在研究期间显示出较短的生存期(3.6、1.0-7.0年vs4.7、0.1-7.0年,P=0.009)比主要等位基因(T)携带者。rs8099917GG患者的死亡风险高于其余患者(GT+TT)(OR1.94,95CI1.11-3.40,P=0.020)。IL12Ars568408中的主要纯合性(基因型GG)与较小等位基因(AAAG)携带者的死亡率更高(HR1.31,95CI1.02-1.69,P=0.035)。在多变量分析中,然而,上述多态性不是生存的独立预测因子.
    结论:IFNL3rs8099917和IL12Ars568408的多态性有助于HD患者的生存,但不是作为独立因素。
    BACKGROUND: Circulating pro-inflammatory cytokines were associated with increased relative mortality risk, while immune parameters reflecting improved T-cell function were predictors of survival in hemodialysis (HD) patients. We evaluated in the prospective study whether variants in T helper cell cytokine-associated genes are determinants of mortality in HD patients.
    METHODS: The study was carried out in 532 prevalent HD subjects who were followed-up for 7 years. HRM analysis was used for IFNL3, IL12A, IL13, and IL4R genotyping. CCL2, IL12B, and IL18 were genotyped using PCR-RFLP analysis. Survival analyses were conducted using the Kaplan-Meier method and the Cox proportional hazard model.
    RESULTS: In univariate analyses, IFNL3 rs8099917 was associated with all-cause mortality in recessive model of inheritance (log-rank test P = 0.044), IL12A rs568408 - in dominant model (log-rank test P = 0.029). Minor homozygotes (the genotype GG) in IFNL3 rs8099917 showed shorter survival during the study (3.6, 1.0-7.0 years vs 4.7, 0.1-7.0 years, P = 0.009) than the major allele (T) bearers. The rs8099917 GG patients demonstrated higher risk of death than the remaining patients (GT + TT) (OR 1.94, 95%CI 1.11-3.40, P = 0.020). Major homozygosity (the genotype GG) in IL12A rs568408 was associated with higher mortality than that shown in bearers of the minor allele (AA + AG) (HR 1.31, 95%CI 1.02-1.69, P = 0.035). In multivariate analyses, however, the mentioned polymorphisms were not independent predictors of survival.
    CONCLUSIONS: Polymorphisms of IFNL3 rs8099917 and IL12A rs568408 contribute to survival of HD patients, but not as independent factors.
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