目的:探讨系统性红斑狼疮(SLE)患者血清白细胞介素-2受体α(IL-2Rα)、5’-寡腺苷酸合成酶1(OAS1)、脱氧核糖核酸酶1Like3(DNase1L3)与疾病活动度和早期肾损伤的关系。方法:纳入我院2018年1月-2021年12月期间收治的113例SLE患者,根据SL...目的:探讨系统性红斑狼疮(SLE)患者血清白细胞介素-2受体α(IL-2Rα)、5’-寡腺苷酸合成酶1(OAS1)、脱氧核糖核酸酶1Like3(DNase1L3)与疾病活动度和早期肾损伤的关系。方法:纳入我院2018年1月-2021年12月期间收治的113例SLE患者,根据SLE疾病活动度评分(SLEDAI)将患者分为轻度组(n=48,SLEDAI评分0~9分)、中度组(n=28,SLEDAI评分10~14分)、重度组(n=37,SLEDAI评分≥15分)。根据患者肾小球滤过率(eGFR)将患者分为肾功能正常组[n=48,eGFR>90 m L/(min·1.73 m_(2))]和早期肾功能损伤组[n=65,eGFR为60~90 m L/(min·1.73 m_(2))]。对比轻度组、中度组和重度组的血清IL-2Rα、OAS1、DNase1L3水平。采用单因素及多因素Logistic回归分析SLE患者早期肾损伤的影响因素。结果:重度组、中度组的IL-2Rα、OAS1高于轻度组,且重度组高于中度组(P<0.05)。重度组、中度组的DNase1L3低于轻度组,且重度组低于中度组(P<0.05)。单因素分析结果显示,SLE患者早期肾损伤与年龄、SLEDAI评分、病程、三酰甘油(TG)、血小板(PLT)、血红蛋白(Hb)、血白蛋白(ALB)、超敏C反应蛋白(hs-CRP)、血尿素氮(BUN)、血肌酐(Scr)、C3、eGFR、血尿酸(UA)、β2微球蛋白(β2MG)、IL-2Rα、OAS1、DNase1L3有关(P<0.05)。多因素Logistic回归分析结果显示年龄、Scr、UA、β2MG、IL-2Rα、OAS1均是SLE患者早期肾损伤的影响因素(P<0.05)。结论:IL-2Rα、OAS1、DNase1L3参与着SLE的疾病进展,其中IL-2Rα、OAS1可与年龄、Scr、UA、β2MG等因素共同辅助评估早期肾功能损伤。展开更多
OASs play critical roles in immune response against virus infection by polymerizing ATP into 2-5 As,which initiate the classical OAS/RNase L pathway and induce degradation of viral RNA.OAS members are functionally div...OASs play critical roles in immune response against virus infection by polymerizing ATP into 2-5 As,which initiate the classical OAS/RNase L pathway and induce degradation of viral RNA.OAS members are functionally diverged in four known innate immune pathways(OAS/RNase L,OASL/IRF7,OASL/RIG-I,and OASL/cGAS),but how they functionally diverged is unclear.Here,we focus on evolutionary patterns and explore the link between evolutionary processes and functional divergence of Tetrapod OAS1.We show that Palaeognathae and Primate OAS1 genes are conserved in genomic and protein structures but differ in function.The former(i.e.,ostrich)efficiently synthesized long 2-5 A and activated RNase L,while the latter(i.e.,human)synthesized short 2-5 A and did not activate RNase L.We predicted and verified that two in-frame indels and one positively selected site in the active site pocket contributed to the functional divergence of Palaeognathae and Primate OAS1.Moreover,we discovered and validated that an in-frame indel in the C-terminus of Palaeognathae OAS1 affected the binding affinity of ds RNA and enzymatic activity,and contributed to the functional divergence of Palaeognathae OAS1 proteins.Our findings unravel the molecular mechanism for functional divergence and give insights into the emergence of novel functions in Tetrapod OAS1.展开更多
文摘目的:探讨系统性红斑狼疮(SLE)患者血清白细胞介素-2受体α(IL-2Rα)、5’-寡腺苷酸合成酶1(OAS1)、脱氧核糖核酸酶1Like3(DNase1L3)与疾病活动度和早期肾损伤的关系。方法:纳入我院2018年1月-2021年12月期间收治的113例SLE患者,根据SLE疾病活动度评分(SLEDAI)将患者分为轻度组(n=48,SLEDAI评分0~9分)、中度组(n=28,SLEDAI评分10~14分)、重度组(n=37,SLEDAI评分≥15分)。根据患者肾小球滤过率(eGFR)将患者分为肾功能正常组[n=48,eGFR>90 m L/(min·1.73 m_(2))]和早期肾功能损伤组[n=65,eGFR为60~90 m L/(min·1.73 m_(2))]。对比轻度组、中度组和重度组的血清IL-2Rα、OAS1、DNase1L3水平。采用单因素及多因素Logistic回归分析SLE患者早期肾损伤的影响因素。结果:重度组、中度组的IL-2Rα、OAS1高于轻度组,且重度组高于中度组(P<0.05)。重度组、中度组的DNase1L3低于轻度组,且重度组低于中度组(P<0.05)。单因素分析结果显示,SLE患者早期肾损伤与年龄、SLEDAI评分、病程、三酰甘油(TG)、血小板(PLT)、血红蛋白(Hb)、血白蛋白(ALB)、超敏C反应蛋白(hs-CRP)、血尿素氮(BUN)、血肌酐(Scr)、C3、eGFR、血尿酸(UA)、β2微球蛋白(β2MG)、IL-2Rα、OAS1、DNase1L3有关(P<0.05)。多因素Logistic回归分析结果显示年龄、Scr、UA、β2MG、IL-2Rα、OAS1均是SLE患者早期肾损伤的影响因素(P<0.05)。结论:IL-2Rα、OAS1、DNase1L3参与着SLE的疾病进展,其中IL-2Rα、OAS1可与年龄、Scr、UA、β2MG等因素共同辅助评估早期肾功能损伤。
基金supported by the National Key Research and Development Program of China(2016YFD0500202)the National Natural Science Foundation of China(31772587)the Plan 111(B12008)。
文摘OASs play critical roles in immune response against virus infection by polymerizing ATP into 2-5 As,which initiate the classical OAS/RNase L pathway and induce degradation of viral RNA.OAS members are functionally diverged in four known innate immune pathways(OAS/RNase L,OASL/IRF7,OASL/RIG-I,and OASL/cGAS),but how they functionally diverged is unclear.Here,we focus on evolutionary patterns and explore the link between evolutionary processes and functional divergence of Tetrapod OAS1.We show that Palaeognathae and Primate OAS1 genes are conserved in genomic and protein structures but differ in function.The former(i.e.,ostrich)efficiently synthesized long 2-5 A and activated RNase L,while the latter(i.e.,human)synthesized short 2-5 A and did not activate RNase L.We predicted and verified that two in-frame indels and one positively selected site in the active site pocket contributed to the functional divergence of Palaeognathae and Primate OAS1.Moreover,we discovered and validated that an in-frame indel in the C-terminus of Palaeognathae OAS1 affected the binding affinity of ds RNA and enzymatic activity,and contributed to the functional divergence of Palaeognathae OAS1 proteins.Our findings unravel the molecular mechanism for functional divergence and give insights into the emergence of novel functions in Tetrapod OAS1.
