系统性红斑狼疮患者血清β2-MG、PGRN、Gas6水平与疾病严重程度和肾脏损害的关系研究

摘要 目的：探讨系统性红斑狼疮患者血清β2-微球蛋白（β2-MG）、颗粒蛋白前体（PGRN）、生长停滞基因6（Gas6）水平与疾病严重程度和肾脏损害的关系。方法：选择2017年1月至2020年12月河北医科大学第二医院风湿免疫科收治的系统性红斑狼疮患者105例,根据系统性红斑狼疮疾病活动度指数(SLEDAI)将患者分为活动期组(SLEDAI≥5分)62例,缓解期组(SLEDAI ≤4分)43例。另取同期于河北医科大学第二医院接受体检的健康志愿者60例作为对照组。比较各组血清β2-MG、PGRN、Gas6、红细胞沉降率（ESR）、C反应蛋白（CRP）、血清补体、抗dsDNA抗体、血尿素氮（BUN）、血肌酐（Scr）,24 h尿蛋白（24h UTP）,并分析其相关性。结果：活动期组β2-MG、PGRN、ESR、CRP、抗dsDNA抗体、BUN、Scr、24 h UTP水平高于缓解期组、对照组,Gas6、血清补体C3、C4水平低于缓解期组、对照组;缓解期组β2-MG、PGRN、ESR、CRP、抗dsDNA抗体、BUN、Scr、24 h UTP水平均高于对照组,Gas6、血清补体C3、C4水平低于对照组,活动期组SLEDAI评分高于缓解期组（P＜0.05）。 Pearson相关性分析可得：系统性红斑狼疮患者血清β2-MG、PGRN与SLEDAI 、ESR、CRP、抗dsDNA、BUN、Scr、24h UTP呈正相关,与血清补体C3、补体C4呈负相关（均P＜0.05）,Gas6水平与SLEDAI、ESR、CRP、抗dsDNA、BUN、Scr、24h UTP呈负相关,与血清补体C3、补体C4呈正相关（均P＜0.05）。结论：系统性红斑狼疮患者血清β2-MG、PGRN水平异常升高,Gas6水平异常降低,且和患者疾病活动程度及肾脏损害密切相关,检测其水平可能为系统性红斑狼疮疾病的评估提供参考。     

系统性红斑狼疮患者血清中CD83与自身抗体的表达及其相互关系

目的：检测系统性红斑狼疮（systemic lupus erythematosus,SLE）患者血清中CD83（soluble CD 83,sCD 83）和多种自身抗体的表达水平,并探讨其相互关系。方法：ELISA检测患者可溶性CD 83和AnuA的表达,应用间接免疫荧光的方法检测抗cmDNA抗体,应用乳凝法检测血清中的DNP,采用胶体金标记和快速膜渗滤技术测定血清中的抗dsDNA抗体。结果：对照组患者血清中可溶性CD 83的表达为（0.26±0.10）ng/ml,实验组患者血清中可溶性CD 83的表达为（5.56±0.72）ng/ml。与对照组相比,实验组患者血清中可溶性CD 83的平均浓度明显升高。在抗dsDNA抗体阴性的51例系统性红斑狼疮患者中AnuA的阳性率明显高于抗DNP抗体和抗cmDNA抗体,同样在抗DNP抗体阴性的58例系统性红斑狼疮患者中AnuA的阳性率明显高于dsDNA抗体和抗cmDNA抗体。系统性红斑狼疮患者中可溶性CD83的水平（〈2.68 ng/ml）与各种自身抗体（抗dsDNA抗体、AnuA、抗DNP抗体和抗cmDNA抗体）水平的相关系数分别为（r=0.542,0.613,0.489和0.367）。具有高水平可溶性CD83的系统性红斑狼疮患者（≥2.68 ng/ml）,与各种自身抗体（抗dsDNA抗体,AnuA,抗DNP抗体和抗cmDNA抗体）水平的相关系数分别为（r=0.711,P〈0.05）、（r=0.845,P〈0.01）、（r=0.862,P〈0.01）和（r=0.724,P〈0.051）。结论：可溶性CD83通过活化DC细胞并激活补体系统,参与系统性红斑狼疮的发生发展,联合可溶性CD83和多种自身抗体的检测,能更明确系统性红斑狼疮患者病情的严重程度,有利于SLE的诊断和治疗。     

血β2微球蛋白水平在系统性红斑狼疮中的临床意义

目的：探讨系统性红斑狼疮（systemic lupus erythematosus,SLE）患者血β2-MG水平与疾病活动的相关性及其临床意义。方法：随机抽取2012年2月-2012年7月我科收治的62例SLE患者（SLE组）和同期在我院门诊体检的健康体检者40例（对照组）,检测和比较两组血清β2-MG、自身抗体、补体水平,并对SLE患者进行SLEDAI评分,分析SLE患者血清β2-MG水平与自身抗体、补体水平和SLEDAI评分的相关性。结果：SLE组血β2-MG水平（3．11±0．40μg／mL）显著高于对照组（2．23±0．23μg/mL）,差异有统计学意义（P〈0．05）;其中发生口腔溃疡、浆膜炎及蛋白尿的SLE患者的血β2-MG水平与无此三种表现的患者相比显著升高,差异有统计学意义（P〈0．05）。SLE患者的血β2-MG水平与抗ds—DAN抗体、SLEDAI均呈显著正相关（分别为r=0．289,r=0．361,P〈0．01）,与C3呈负相关（r=-0．271,P〈0．05）。结论：SLE患者血β2-MG水平高于正常,可作为SLE疾病活动指标用于监测疾病活动。     

FcγRb和Clq抗体的变化在系统性红斑狼疮中的意义

目的探讨系统性红斑狼疮(SLE)患者外周血单个核细胞FcγRb及血清Clq抗体的表达在SLE发病机制中的意义。方法41例SLE和30例正常人外周血粒细胞、淋巴细胞和单核细胞FcγRb的表达,采用流式细胞仪测定,血清Clq抗体采用ELISA法测定,FcγRb和Clq抗体的表达,分别与抗核抗体(ANA)、dsDNA抗体及SLEDAI评分作相关性分析。结果SLE患者外周血粒细胞、淋巴细胞和单核细胞FcγRb的表达均减少,以粒细胞和单核细胞为主,血清Clq抗体水平明显增高,FcγRb和Clq抗体与ANA、抗dsDNA及系统性红斑狼疮活动指数(SLEDAI)评分,分别呈负相关和正相关;FcγRb与Clq抗体呈低-中度负相关。结论SLE患者外周血单个核细胞FcγRb表达缺陷和血清Clq抗体水平升高,使免疫复合物的清除功能下降,在SLE的免疫发病机制中起重要作用,FcγRb和Clq抗体是判断病情活动性的重要指标。     

FcγRⅡb和Clq抗体的变化在系统性红斑狼疮中的意义

目的探讨系统性红斑狼疮(SLE)患者外周血单个核细胞FcγRⅡb及血清Clq抗体的表达在SLE发病机制中的意义。方法41例SLE和30例正常人外岗血粒细胞、淋巴细胞和单核细胞FcγRⅡb的表达。采用流式细胞仪测定,血清Clq抗体采用ELISA法测定,FcγRⅡb和Clq抗体的表达．分别与抗核抗体(ANA)、dsDNA抗体及SLEDAI评分作相关性分析。结果SLE患者外周血粒细胞、淋巴细胞和单核细胞FcγRⅡb的表达均减少,以粒细胞和单核细胞为主,血清Clq抗体水平明显增高FcγRⅡb和Clq抗体与ANA、抗dsDNA及系统性红斑狼疮活动指数(SLEDAI)评分。分别呈负相关和正相关;FcγRⅡb与Clq抗体呈低一中度负相关。结论SLE患者外周血单个核细胞FcγRⅡb表达缺陷和血清Clq抗体水平升高。使免疫复合物的清除功能下降,在SLE的免疫发病机制中起重要作用,FcγRⅡb和Clq抗体是判断病情活动性的重要指标。     

系统性红斑狼疮患者血小板参数、血脂、补体C3、C4水平与病情活动度的关系分析

摘要 目的：研究系统性红斑狼疮（SLE）患者血小板参数、血脂、补体C3、C4水平与病情活动度的关系。方法：将从2011年1月～2018年1月我院收治的100例SLE患者纳入研究,将其按照SEL疾病活动指数（SLEDAI）评分的不同分成活动组（SLEDAI评分≥10分）36例,非活动组（SLEDAI评分<10分）64例,另取同期于我院进行体检的健康志愿者100例作为对照组。比较三组各项血小板参数、血脂指标以及补体C3、C4水平,采用Pearson相关性分析SLE患者SLEDAI评分与各项指标的相关性。结果：活动组、非活动组血小板计数（PLT）、血小板压积、大血小板百分率低于对照组,且活动组PLT、大血小板百分率低于非活动组（P<0.05）。活动组、非活动组血小板平均容积（MPV）、血小板体积分布宽度（PDW）高于对照组,且活动组高于非活动组（P<0.05）。活动组、非活动组低密度脂蛋白胆固醇（LDL-C）均高于对照组,高密度脂蛋白胆固醇（HDL-C）均低于对照组（P<0.05）,活动组HDL-C低于非活动组（P<0.05）。活动组、非活动组补体C3、C4水平均低于对照组,且活动组补体C3、C4水平均低于非活动组（P<0.05）。经Pearson相关性分析发现：SLE患者SLEDAI评分与PLT、大血小板百分率、HDL-C以及补体C3、C4水平呈负相关,与MPV、PDW呈正相关（P<0.05）。结论：SLE患者血小板参数PLT、大血小板百分率、血脂指标HDL-C以及补体C3、C4水平与SLEDAI评分密切相关,可能作为SLE患者疾病活动性的评估指标。     

系统性红斑狼疮患者血清中CD83 与自身抗体的表达及其相互关系

目的:检测系统性红斑狼疮(systemic lupus erythematosus,SLE)患者血清中 CD83(soluble CD 83,sCD 83)和多种自身抗体的表达水平,并探讨其相互关系.方法:ELISA 检测患者可溶性 CD 83 和AnuA的表达,应用间接免疫荧光的方法检测抗cmDNA 抗体,应用乳凝法检测血清中的DNP,采用胶体金标记和快速膜渗滤技术测定血清中的抗 dsDNA 抗体.结果:对照组患者血清中可溶性 CD83 的表达为(0.26±0.10)ng/ml,实验组患者血清中可溶性 CD83 的表达为(5.56±0.72)ng/mI.与对照组相比,实验组患者血清中可溶性CD 83的平均浓度明显升高.在抗dsDNA抗体阴性的 51 例系统性红斑狼疮患者中 AnuA 的阳性率明显高于抗DNP 抗体和抗 cmDNA 抗体,同样在抗 DNP 抗体阴性的 58 例系统性红斑狼疮患者中 AnuA 的阳性率明显高于 dsDNA 抗体和抗 cmDNA 抗体.系统性红斑狼疮患者中可溶性 CD83 的水平(<2.68 ng/ml)与各种自身抗体(抗 dsDNA 抗体、AnuA、抗DNP抗体和抗 cmDNA 抗体) 水平的相关系数分别为(r＝0.542,0.613,0.489和0.367).具有高水平可溶性CD83的系统性红斑狼疮患者( ≥2.68 ng/ml),与各种自身抗体(抗dsDNA抗体,AnuA,抗 DNP 抗体和抗cmDNA 抗体)水平的相关系数分别为(r＝0.711,P<0.05)、(r＝0.845,P<0.01)、(r=0.862,P<0.01)和(r=0.724,P<0.051).结论:可溶性CD83通过活化DC细胞并激活补体系统,参与系统性红斑狼疮的发生发展,联合可溶性 CD83 和多种自身抗体的检测,能更明确系统性红斑狼疮患者病情的严重程度,有利于 SLE 的诊断和治疗.     

CXCR1和CXCR2在系统性红斑狼疮中的表达及意义

目的:检测白介素-8受体CXCR1和CXCR2在系统性红斑狼疮(SLE)患者外周血CD14+单核细胞上的表达,探讨其与SLE疾病活动的相关性和可能涉及的SLE炎症发病机制.方法:36例活动期SLE患者和34例健康志愿者,采用流式细胞术(FCM)检测CXCR1、CXCR2在SLE患者和健康志愿者外周血CD14+单核细胞上的MFI表达.结果:CXCR2在SLE组外周血CD14+单核细胞上MFI表达(195.75±52.76)与对照组(298.82±51.86)相比明显降低(P＜0.01);CXCR2在SLE患者外周血CD14+单核细胞上MFI表达下降与C3存在着正相关关系(rs=0.421,P=0.022),与dsDNA、SLEDAI存在着负相关关系(分别为rs=-0.390,P=0.032;rs=-0.463,P=0.011).结论:SLE患者外周血CD14+单核细胞CXCR2的表达异常,提示CXCR2可能参与了SLE的发病过程.检测SLE患者外周血CD14+单核细胞的CXCR2表达水平,可能是评价SLE疾病活动性有价值的潜在的生物学标志之一.     

GPⅡb/Ⅲa抗体及ACA在系统性红斑狼疮血小板减少患者中临床意义探讨

目的:探讨血小板膜糖蛋白(GP) Ⅱb/Ⅲa抗体及抗心磷脂抗体(ACA)在系统性红斑狼疮血小板减少(SLE-TP)患者中的临床意义.方法:采用酶联免疫吸附试验(ELISA)法检测SLE血小板减少组35例、非血小板减少组27例、ITP组14例及健康对照组16例血清中抗GP Ⅱb/Ⅲa抗体及ACA的水平,分析其与SLE-TP患者临床、实验室指标及SLEDAI评分的相关性;统计方法采用x2检验、Fisher确切概率法.结果:①SLE血小板减少组抗GP Ⅱb/Ⅲa抗体表达水平显著高于非血小板减少组及健康对照组(P＜0.01);②抗GP Ⅱb/Ⅲa抗体在SLE血小板减少组与ITP组间的表达差异无统计学意义;③各组间ACA阳性率差异无统计学意义;④在SLE血小板减少组,抗GP Ⅱb/Ⅲa抗体与SLEDAI评分等级有显著关联(P＜0.05),与血小板减少程度、皮疹、光过敏、脾大、关节炎、粒细胞减少、肾脏及神经系统受累等临床指标无相关性,与dsDNA、Sm、SS-A、C3、C4、Coombs实验及ACA无显著关联.结论:SLE-TP患者血清中抗GP Ⅱb/Ⅲa抗体高表达,且与疾病的活动呈正相关,可能在SLE-TP的发病过程中发挥了重要作用.     

系统性红斑狼疮外周血单个核细胞cFLIP—L mRNA和cFLIP—S mRNA表达的研究

目的探讨系统性红斑狼疮（system lupus erythematosus,SLE）患者外周血单个核细胞（peripheral blood monouuclear cells,PBMC）中细胞型Fas相关死亡域样白介素-1β转换酶抑制蛋白（cFLIP）表达的意义。方法应用半定量RT—PCR方法检测38例SLE患者和21名正常人PBMC中cFLIP—L mRNA和cFLIP—S mRNA的表达水平,并与SLE疾病活动指数（SLEDAI）评分进行相关性分析。结果①SLE患者PBMC中cFLIP—L mRNA和cFLIP—S mRNA表达水平均明显高于正常对照组（P〈0．01）;SLE患者活动组cFLIP—L mRNA表达水平显著高于非活动组（P〈0．05）,cFLIP—S mRNA表达水平在SLE患者活动组与非活动组之间没有显著性差异（P〉0．05）。②SLE患者cFLIP—L mRNA表达水平与SLEDAI评分呈正相关（r=0．423,P〈0．01）;而eFLIP—S mRNA表达水平与SLEDAI评分无明显相关性（r=0．270,P〉0．05）。结论cFLIP—L mRNA和cFLIP—S mRNA可能在SLE发病机制中起重要作用。     

Deficiency of functional mannose-binding lectin is not associated with infections in patients with systemic lupus erythematosus

Infection imposes a serious burden on patients with systemic lupus erythematosus (SLE). The increased infection rate in SLE patients has been attributed in part to defects of immune defence. Recently, the lectin pathway of complement activation has also been suggested to play a role in the occurrence of infections in SLE. In previous studies, SLE patients homozygous for mannose-binding lectin (MBL) variant alleles were at an increased risk of acquiring serious infections in comparison with patients who were heterozygous or homozygous for the normal allele. This association suggests a correlation between functional MBL level and occurrence of infections in SLE patients. We therefore investigated the biological activity of MBL and its relationship with the occurrence of infections in patients with SLE. Demographic and clinical data were collected in 103 patients with SLE. Functional MBL serum levels and MBL-induced C4 deposition were measured by enzyme-linked immunosorbent assay using mannan as coat and an MBL- or C4b-specific monoclonal antibody. The complete MBL-dependent pathway activity was determined by using an assay that measures the complete MBL pathway activity in serum, starting with binding of MBL to mannan, and was detected with a specific monoclonal antibody against C5b-9. Charts were systematically reviewed to obtain information on documented infections since diagnosis of SLE. Major infections were defined as infections requiring hospital admission and intravenous administration of antibiotics. In total, 115 infections since diagnosis of lupus, including 42 major infections, were documented in the 103 SLE patients (mean age 41 ± 13 years, mean disease duration 7 ± 4 years). The percentage of SLE patients with severe MBL deficiency was similar to that in 100 healthy controls: 13% versus 14%, respectively. Although deposition of C4 to mannan and MBL pathway activity were reduced in 21% and 43% of 103 SLE patients, respectively, neither functional MBL serum levels nor MBL pathway activity was associated with infections or major infections in regression analyses. In conclusion, SLE patients frequently suffer from infections, but deficiency of functional MBL does not confer additional risk.     

Deficiency of functional mannose-binding lectin is not associated with infections in patients with systemic lupus erythematosus

Infection imposes a serious burden on patients with systemic lupus erythematosus (SLE). The increased infection rate in SLE patients has been attributed in part to defects of immune defence. Recently, the lectin pathway of complement activation has also been suggested to play a role in the occurrence of infections in SLE. In previous studies, SLE patients homozygous for mannose-binding lectin (MBL) variant alleles were at an increased risk of acquiring serious infections in comparison with patients who were heterozygous or homozygous for the normal allele. This association suggests a correlation between functional MBL level and occurrence of infections in SLE patients. We therefore investigated the biological activity of MBL and its relationship with the occurrence of infections in patients with SLE. Demographic and clinical data were collected in 103 patients with SLE. Functional MBL serum levels and MBL-induced C4 deposition were measured by enzyme-linked immunosorbent assay using mannan as coat and an MBL- or C4b-specific monoclonal antibody. The complete MBL-dependent pathway activity was determined by using an assay that measures the complete MBL pathway activity in serum, starting with binding of MBL to mannan, and was detected with a specific monoclonal antibody against C5b-9. Charts were systematically reviewed to obtain information on documented infections since diagnosis of SLE. Major infections were defined as infections requiring hospital admission and intravenous administration of antibiotics. In total, 115 infections since diagnosis of lupus, including 42 major infections, were documented in the 103 SLE patients (mean age 41 +/- 13 years, mean disease duration 7 +/- 4 years). The percentage of SLE patients with severe MBL deficiency was similar to that in 100 healthy controls: 13% versus 14%, respectively. Although deposition of C4 to mannan and MBL pathway activity were reduced in 21% and 43% of 103 SLE patients, respectively, neither functional MBL serum levels nor MBL pathway activity was associated with infections or major infections in regression analyses. In conclusion, SLE patients frequently suffer from infections, but deficiency of functional MBL does not confer additional risk.     

系统性红斑狼疮并发低T3综合征的影响因素分析

目的:探讨系统性红斑狼疮并发低T3综合征的影响因素。方法:选择2102年6月~2013年6月于我科住院的SLE女性患者60例,其中伴有低T3综合征的30例(排除具有原发性甲状腺疾病的病例),甲状腺功能正常的30例,分析和比较伴有低T3综合征的SLE患者与甲状腺功能正常的SLE患者入院时的血常规、C反应蛋白、血沉、肝功能、肾功能、补体C3、补体C4、24小时尿蛋白等实验室指标和临床特征,并通过单因素和多因素Logistic回归分析探讨系统性红斑狼疮并发低T3综合征的影响因素。结果:伴有低T3综合征的SLE患者SLEDAI积分、红细胞计数、血红蛋白、血小板、补体C3、白蛋白、谷丙转氨酶、尿素、24小时尿蛋白定量与甲状腺功能正常的SLE患者比较均有统计学差异(P0.05);Logistic回归分析显示SLEDAI积分(OR=2.194,1.045~4.606,P=0.038)、血红蛋白(OR=0.719,0.518~0.998,P=0.049)、谷丙转氨酶(OR=2.417,1.071~5.457,P=0.034)、白蛋白(OR=0.313,0.105~0.934,P=0.037)是系统性红斑狼疮并发低T3综合征的影响因素。结论:SLEDAI积分和谷丙转氨酶水平是系统性红斑狼疮并发低T3综合征的危险性因素,而血红蛋白和白蛋白水平是其保护性因素。     

MBL在结肠直肠癌中的基因分型

目的：MBL是补体激活凝集素途径的关键因素。MBL基因多态性影响MBL血清水平。结肠直肠癌患者血清MBL水平升高。低水平的MBL则预示着术后肺炎的发生,目前还不清楚此相关性是否与遗传相关。本实验分析调查了结肠直肠癌患者和健康对照者的MBL基因分型,评估基因分析和复发率、生存率之间潜在的相关性。方法：使用TaqMan基因分型分析法和实时定量PCR分析MBL基因的4个SNP、启动子区2个SNP、非编码区1个SNP;ELISA测定标本血清MBL含量。结果：所有标本中发现了8种不同的MBL单体型,它们在患者和健康者中出现频率几乎是完全一样的;YA/YA基因型与高水平的MBL相关,YO／YO与低水平的MBL水平相关,6种不同基因型CRC患者的MBL水平存在着明显不同。结论：MBL基因型与血清MBL浓度显薯相关（P〈0．0001）;突变型B,C,D和启动子单体型Y,X对MBL含量的影响起主要作用;MBL基因型和术后感染并发症没有明显相关性（P=0．33）,与复发癌和存活时间也没有明显相关性（P=0．74）。因此,从基因水平还不能解释为何结肠直肠癌患者血清MBL水平增加。对比已经检测出的血清MBL水平,其基因型还不能预测结肠直肠癌患者的疾病进程。     

Mannose binding lectin: a biomarker of systemic lupus erythematosus disease activity

Introduction

A role for mannose binding lectin (MBL) in autoimmune diseases has been demonstrated earlier and elevated level of MBL has been shown in systemic lupus erythematosus (SLE) patients. In the current study, we investigated MBL as a potential biomarker for disease activity in SLE.

Methods

In a case control study SLE patients (93 females) and 67 age, sex, ethnicity matched healthy controls were enrolled. Plasma MBL levels were quantified by enzyme linked immunosorbent assay (ELISA). Clinical, serological and other markers of disease activity (C3, C4 and anti-dsDNA) were measured by standard laboratory procedures.

Results

Plasma MBL levels were significantly high in SLE patients compared to healthy controls (P < 0.0001). MBL levels were variable in different clinical categories of SLE. Lower levels were associated with musculoskeletal and cutaneous manifestations (P = 0.002), while higher and intermediate MBL levels were significantly associated with nephritis in combination with other systemic manifestations (P = 0.01 and P = 0.04 respectively). Plasma MBL correlated with systemic lupus erythematosus disease activity index (SLEDAI) (P = 0.0003, r = 0.36), anti-dsDNA (P < 0.0001, r = 0.54), proteinuria (P < 0.0001, r = 0.42) and negatively correlated with C3 (P = 0.007, r = -0.27) and C4 (P = 0.01, r = -0.29).

Conclusions

Plasma MBL is a promising marker in the assessment of SLE disease activity.     

血钙对老年肺炎患者的严重程度及预后的影响

目的：研究血清钙离子浓度与老年肺炎患者的严重程度及预后的关系。方法：按照脓毒症的诊断标准将入住急诊ICU的老年肺炎患者206例,分为脓毒症组（155例）和非脓毒症组（51例）,脓毒症组又按照预后分为存活组（91例）和死亡组（64例）。分别测定血清钙离子浓度、血浆白蛋白、C-反应蛋白（CRP）、血白细胞计数等有关的实验室指标,比较2组指标的差别。结果：脓毒症组中血清钙离子浓度较非脓毒症组降低,CRP、血白细胞计数较非脓毒症组升高（P〈0．01）;亚组分析中,死亡组中血清钙离子浓度较存活组降低（P〈0．01）,CRP较存活组升高（P〈0．05）,血白细胞计数两组比较无明显差异（P〉0．05）;血清钙离子浓度与血浆白蛋白的浓度呈高度正相关。结论：血清钙离子浓度对判断老年肺炎患者的预后有一定的临床意义。     

Co-Positivity for Anti-dsDNA, -Nucleosome and -Histone Antibodies in Lupus Nephritis Is Indicative of High Serum Levels and Severe Nephropathy

ObjectiveTo characterize the significance of correlated autoantibodies in systemic lupus erythematosus (SLE) and its complication lupus nephritis (LN) in a large cohort of patients.MethodsClinical data were statistically analyzed in 1699 SLE patients with or without nephritis who were diagnosed and treated during 2002–2013 in the northeast region of China. Reactivity to a list of 16 autoantibodies was detected by the serum test Euroline ANA profile (IgG). Serum titers of the anti-nucleosome autoantibodies were measured by ELISA assays. Kidney biopsies were examined by pathologists. Immune complex deposition was identified by immunohistochemistry stain.ResultsSimultaneous positivity of anti-dsDNA, -nucleosome and -histone antibodies (3-pos) was prevalent in SLE patients with LN compared to Non-renal SLE patients (41% vs 11%, p< 0.001). Significant correlations were found between any two of the above three anti-nucleosome antibodies in LN patients. In comparison to non-3-pos cohorts, 3-pos patients with LN had significantly higher serum levels of the three antibodies and more active disease; was associated with type IV disease; suffered from more severe renal damages; received more intensive treatment and had worse disease outcome. The serum levels of these three autoantibodies in 3-pos LN patients were significantly decreased when they underwent clinical recovery.ConclusionsSimultaneous reactivity to anti-dsDNA, -nucleosome and -histone antibodies by Euroline ANA profile (IgG) may indicate severe nephropathy in patients with SLE.     

Type I Interferon-Mediated Skewing of the Serotonin Synthesis Is Associated with Severe Disease in Systemic Lupus Erythematosus

Serotonin, a highly pro-inflammatory molecule released by activated platelets, is formed by tryptophan. Tryptophan is also needed in the production of kynurenine, a process mediated by the type I interferon (IFN)-regulated rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO). The aim of this study was to investigate levels of serotonin in patients with the autoimmune disease systemic lupus erythematosus (SLE), association to clinical phenotype and possible involvement of IDO in regulation of serotonin synthesis. Serotonin levels were measured in serum and plasma from patients with SLE (n=148) and healthy volunteers (n=79) by liquid chromatography and ELISA, as well as intracellularly in platelets by flow cytometry. We found that SLE patients had decreased serotonin levels in serum (p=0.01) and platelets (p<0.0001) as compared to healthy individuals. SLE patients with ongoing type I IFN activity, as determined by an in-house reporter assay, had decreased serum levels of serotonin (p=0.0008) as well as increased IDO activity (p<0.0001), as determined by the kynurenine/tryptophan ratio measured by liquid chromatography. Furthermore, SLE sera induced IDO expression in WISH cells in a type I IFN-dependent manner (p=0.008). Also platelet activation contributed to reduce overall availability of serotonin levels in platelets and serum (p<0.05). Decreased serum serotonin levels were associated with severe SLE with presence of anti-dsDNA antibodies and nephritis. In all, reduced serum serotonin levels in SLE patients were related to severe disease phenotype, including nephritis, suggesting involvement of important immunopathological processes. Further, our data suggest that type I IFNs, present in SLE sera, are able to up-regulate IDO expression, which may lead to decreased serum serotonin levels.