血浆可溶型人类白细胞抗原-G在系统性红斑狼疮患者中的表达分析

目的 检测系统性红斑狼疮(SLE)患者血浆可溶性人类白细胞抗原-G(sHLA-G)水平,并分析其与SLE脏器受累及疾病活动性的关系,探讨sHLA-G在SLE发病机制中的可能作用.方法 酶联免疫吸附法(ELISA)检测96例SLE患者血浆sHLA-G水平,并与74名健康体检者对照.采用t检验,直线相关回归方法 和X2检验,P<0.05为差异有统计学意义.结果血浆sHLA-G水平在SLE患者为(230±192)U/ml;显著高于健康体检者的(118±38)U/ml(t=5.07,P=0.0001);血浆sHLA-G水平与SLE疾病活动性指数(SLEDIA)无明显相关性(r=0.157,P=0.141);但血浆sHLA-G水平增高的SLE患者较血浆sHLA-G水平正常患者SLEDAI高(11±5与8±5,P=0.027),易出现中枢神经系统受累(24.2%与4.8%,P=0.007).结论 血浆sHLA-G水平增高SLE患者病情较重、中枢神经系统受累较多,提示sHLA-G在SLE病理过程中可能发挥重要作用.     

系统性红斑狼疮趋化因子CXCL13水平升高的临床意义

目的 探讨趋化因子CXCL13在系统性红斑狼疮(systemic lupus erythematosus,SLE患者血浆中的表达及临床意义。方法 收集SLE患者60例,健康对照20例,采用酶联免疫吸附法(ELISA)检测两组血浆中CXCL13的表达水平,并分析与SLE患者实验室指标及疾病活动度的关系;同时比较血浆CXCL13水平在狼疮性肾炎(lupus nephritis,LN)和非LN患者间的表达差异;受试者工作特征曲线(ROC曲线)判断血浆CXCL13对诊断LN的敏感性和特异性。采用t检验、Kruskal-Wallis H检验、Pearson相关分析进行统计学数据分析。结果 SLE患者血浆CXCL13为(272. 1±232. 7) pg/ml,明显高于健康对照组(52. 1±31. 0) pg/ml (P 0. 05)。LN患者血浆CXCL13水平为(340. 9±248. 6) pg/ml,明显高于非LN患者[(134. 5±106. 9) pg/ml; Z=3. 895,P 0. 01]。血浆CXCL13水平与SLE患者SLEDAI评分呈正相关(r=0. 267,P 0. 05),与补体C3 (r=-0. 294,P 0. 05)、外周血血红蛋白含量(r=-0. 299,P 0. 05)、血小板计数(r=-0. 300,P 0. 05)、淋巴细胞计数(r=-0. 309,P 0. 05)呈负相关。疾病活动组患者血浆CXCL13水平明显高于疾病稳定组[(335. 7±248. 2) pg/ml比(144. 9±127. 5) pg/ml,t=3. 223,P 0. 01]。抗ds DNA抗体阳性组血浆CXCL13水平明显高于抗ds DNA抗体阴性组[(367. 0±285. 4) pg/ml比(204. 3±158. 6) pg/ml,t=2. 824,P 0. 01]; AHA阳性组血浆CXCL13水平明显高于AHA阴性组[(375. 3±276. 8) pg/ml比(216. 5±186. 3) pg/ml; t=2. 645,P 0. 05]。LN患者血浆CXCL13水平与血清尿素氮呈正相关(r=0. 425,P 0. 01),与e GFR呈负相关(r=-0. 385,P 0. 05)。血浆CXCL13水平≥116. 95 pg/ml,对LN诊断的敏感性为92. 5%,特异性为60. 0%。结论 SLE患者血浆CXCL13水平明显升高,可能与自身抗体产生及血液系统和肾脏系统损害有关,CXCL13可作为判断SLE疾病活动性的指标之一。     

系统性红斑狼疮患者外周血白细胞介素-17与辅助T细胞17的检测及其意义

目的 研究系统性红斑狼疮(SLE)患者外周血白细胞介素(IL)-17蛋白和mRNA水平、辅助T细胞(Th17)细胞表达比例,探讨其临床意义.方法 用酶联免疫吸附试验检测SLE患者及对照者血浆中IL-17的蛋白水平;采用实时荧光定量反转录-聚合酶链式反应(RT-PCR)检测2组外周血中IL-17 mRNA表达水平;运用流式细胞术检测SLE患者外周血单个核细胞(PBMCs)中Th17细胞比例,进一步分析IL-17/Th17细胞与SLE临床实验室指标的相关性.计量资料组间比较采用t检验,相关性分析采用Spearman秩和相关分析.结果 SLE组患者血浆IL-17含量明显高于健康对照组,SLE组患者外周血IL-17 mRNA表达水平[(28.3±11.7)×10-5]高于对照组[(9.8±2.2)×10-5](P均＜0.01).SLE患者PBMCs中Th17细胞比例(2.5±1.5)%及IL-17荧光强度(1937±1022)显著高于对照组[(1.5±0.7)%,(1245±413)],且SLE活动期患者Th17细胞百分比高于非活动组,SLE肾病组Th17细胞比例较无肾病组明显升高(P均＜0.05).SLE患者血浆IL-17水平、Th17细胞数与SLE疾病活动性指数(SLEDAI)呈正相关(r=0.681,P＜0.01;r=0.426,P=0.034).结论 SLE患者体内IL-17蛋白分泌及基因表达水平存在明显异常,外周血Th17细胞比例亦显著升高,且与疾病活动性有明显相关,提示IL-17/Th17细胞可能在SLE发病中起着重要作用.     

系统性红斑狼疮患者外周血单个核细胞微管相关蛋白1轻链3 mRNA表达水平及其意义

目的 通过检测系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMCs)中微管相关蛋白1轻链3 (LC3)表达,探讨其与SLE发病的关系.方法 选56例SLE患者(SLE组)和45例健康体检者(对照组),应用实时定量PCR检测2组受试者PBMCs中LC3 mRNA表达水平,同时采用流式细胞术检测2组受试者PBMCs自噬发生情况,进一步分析LC3 mRNA表达水平与自噬发生、SLE患者临床特点及病情活动度的相关性.结果 SLE患者PBMCs中LC3 mRNA表达水平为1.30±0.10,低于对照组(1.35 ±0.09;P =0.029).SLE患者PBMCs自噬发生率为(2.21±1.07)％,显著低于对照组[(9.91±4.01)％;P=0.047].PBMCs中LC3 mRNA表达水平与PBMCs自噬发生率存在相关性(r=0.735,P=0.003).PBMCs中LC3 mRNA表达水平＜1.351者SLE疾病活动指数为10.7±2.8,85.2％(23/27)的患者出现肾脏受累,而关节炎、浆膜炎和血液系统损害发生率虽有增高趋势,但差异无统计学意义.结论 SLE患者PBMCs中LC3 mRNA表达减少,导致自噬形成障碍,致使不能有效清除衰老、变性的生物分子,提示自噬在SLE发病及病情进展中发挥重要作用.     

干扰素调节因子5在系统性红斑狼疮的表达及临床相关性研究

目的 比较干扰素调节因子5(IRF5)mRNA在系统性红斑狼疮(SLE)患者和健康对照组的表达水平,分析IRF5表达与SLE疾病活动性及自身抗体和临床症状的相关性.方法 Ficoll密度梯度离心法分离SLE患者及健康对照外周血单个核细胞(PBMC),Trizol法分离提取总RNA,反转录mRNA为eDNA;实时定量聚合酶链反应(PCR)法测定SLE患者和正常对照组IRF5表达量;并分析SLE患者IRF5表达量与疾病活动性及临床症状的相关性.结果 SLE组IRF5表达量(2.1+2.2)高于正常对照组(1.5±1.2),但差异无统计学意义(P=0.161);SLE患者IRF5表达量与其疾病活动指数(SLEDAI)显著相关(r=0.616,P<0.01);SLE患者中抗dsDNA抗体阳性组IRF5表达量(3.2±2.8)明显高于抗体阴性组(1.3±1.6).差异有统计学意义(P=0.018);SLE患者有发热、神经精神症状者IRF5表达量明显高于无此类临床症状者.结论 IRF5在SLE患者中表达偏高,且与SLEDAI显著相关,其可能通过调节下游基因的转录表达诱一导免疫失调,并由此参与SLE的发病过程.     

趋化因子CXCL12-3’G801A多态性与系统性红斑狼疮的相关性

目的检测系统性红斑狼疮(systemic lupus erythematosus,SLE)患者趋化因子CXCL12-3’G801A基因型分布,探索该基因变异对SLE的易感性及临床表现、自身抗体生成等的影响。方法用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测298例中国汉族SLE患者及243名健康对照者的CXCL12-3’G801A基因型,进行Hardy-Weinberg平衡、组间等位基因及基因型频率比较,分析不同基因型SLE患者的临床特征及实验室检查结果。结果 CXCL12-3’801G/G纯合子频率在SLE患者中明显增高(P=0.015),同时携带该基因型的SLE患者易出现光敏感(P=0.014)及肾脏损害(P=0.009),且SLE疾病活动性积分显著增高(P=0.048),抗dsDNA抗体(P=0.004)、抗核小体抗体(P=0.003)阳性率亦明显高于其他基因型患者。结论 CXCL12-3’G801A基因变异参与中国汉族人群SLE疾病易感性过程,并可通过影响自身抗体的生成而影响SLE患者的临床表现及疾病活动性。     

趋化因子积分是系统性红斑狼疮活动和损伤的生物标志物

目的 探讨趋化因子积分与系统性红斑狼疮(SLE)临床特征的相关性.方法 采用实时定量聚合酶链反应(PCR)技术检测60例SLE患者,20例类风湿关节炎(RA)患者及23名健康对照外周血白细胞中7个趋化因子[RANTES、单核细胞趋化因子(MCP)-1、CCL19、MIG、IP-10、CXCL11和白细胞介素(IL)-8]的mRNA表达水平,计算趋化因子积分,并将其与相应的临床资料进行统计学分析.结果 趋化因子积分在SLE患者中较疾病和健康对照显著增高(P=0.0112和P=0.0019);趋化因子积分与SLEDAl积分呈正相关(P=0.0061),与补体C3水平呈负相关(P=0.003);与无肾炎病史患者相比,趋化因子积分在活动性狼疮肾炎(LN)患者中显著增高,特别在泼尼松用量＜30 mgCd时(P=0.0418及P=0.002);趋化因子积分还与慢性损伤指数(SDI)相关;此外,在抗Sm、抗RNP抗体阳性的患者中也存在趋化因子积分显著升高.结论 趋化因子积分与SLE的疾病活动性、脏器损伤的出现和严重程度以及特定的自身抗体表型相关,是SLE新的生物标志物.     

系统性红斑狼疮患者外周血单个核细胞中微管相关蛋白轻链3和溶酶体相关膜蛋白2基因表达及其临床意义

目的检测系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMCs)中巨自噬标志性分子微管相关蛋白轻链3 (LC3)和分子伴侣介导的自噬(CMA)标志性分子溶酶体相关膜蛋白2(LAMP-2)基因表达,探讨其与SLE发病的关系。方法纳入2017年11月至2018年3月在川北医学院附属医院风湿免疫科诊治的88例SLE患者(SLE),采用密度梯度离心法分离外周血单个核白细胞(PBMCs);采用实时荧光定量PCR法测定患者PBMCs中LC3和LAMP-2在mRNA水平的表达量;采用SLE疾病活动指数(SLEDAI)评分判断疾病活动度,分析LC3和LAMP-2表达与SLE患者临床特点及病情活动度的相关性。同期纳入年龄匹配的40例健康体检者作为正常对照组。结果正常对照组受检者PBMCs中LC3 mRNA和LAMP-2 mRNA相对表达量分别为1. 021±0. 551和1. 015±0. 667,SLE组患者分别为0. 783±0. 435和2. 402±2. 233,组间比较差异均有统计学意义(P=0. 020、0. 000)。SLE患者PBMCs中LAMP-2 mRNA表达水平与SLEDAI呈明显正相关(rs=0. 312,P=0. 003),LC3mRNA表达水平与SLEDAI无明显相关性(rs=-0. 175,P=0. 103)。LAMP-2 mRNA表达量升高患者肾脏损害发生率明显高于非升高患者(40. 7%vs. 16. 3%),LC3 mRNA表达量降低患者的血液系统受累率明显高于无LC3 mRNA表达降低患者(65. 2%vs. 32. 3%),差异均有统计学意义(P=0. 013、0. 006)。不同LC3 mRNA和LAMP-2 mRNA表达水平组实验室检查指标和治疗效果的患者分布差异均无统计学意义(均P0. 05)。结论 SLE患者LC3 mRNA表达水平下调,LAMP-2 mRNA表达水平上调,提示SLE患者存在巨自噬功能不足。SLE患者CMA功能增强,并且与肾脏和血液系统受累有关。     

趋化因子CXCL9基因SNPrs2276886与系统性红斑狼疮相关性研究

目的 分析趋化因子CXCL9基因SNPrs2276886在中国汉族人群中的分布情况以及与系统性红斑狼疮(SLE)遗传易感性的关系.方法 ①抽提482例SLE患者[其中包括253例狼疮肾炎(LN)患者]外周血DNA,经聚合酶链反应(PCR)扩增后,通过Pyrosequeneing法进行等位基因分型.②80例患者同时留取RNA样本并反转录为cDNA,以实时荧光定量PCR方法检测NCXCL9基因的表达水平.结果 SLE组和LN组等位基因T的频率高于正常对照组(OR分别为1.346和1.347,P＜0.05),TT基因型的频率也显著高于正常人群(x2分别是6.397和3.941,P＜0.05).CXCL9 mRNA在rs2276886 TT型个体中的表达(3.9±2.0)高于CC型纯合子(2.5±2.1),P＜O.05.结论 证实了中国人群中CXCL9基因SNPrs2276886作为一种遗传因素影响对疾病的易感性,等位基因T对于SLE是一种遗传易感标记.该SNP可能从转录水平上决定了基因的分泌水平,从而参与SLE的发病.     

IKB激酶在系统性红斑狼疮患者中表达及与干扰素-α产生的关系

目的 研究系统性红斑狼疮(SEE)患者外周血白细胞中IKB激酶(IKK-α)、干扰素(IFN)-αmRNA的表达,并检测血浆中IFN-α的水平,以探讨SLE患者中IKK-α在IFN-α产生中的作用.方法 SYBR green dye I实时定量聚合酶链反应(PCR)方法检测外周血白细胞IKK-α和IFN-α的表达;酶联免疫吸附试验(ELISA)法检测血清IFN-α的水平.结果 ①SLE患者外周血IKK-α mRNA表达高于对照组(P<0.05);在活动组SLE患者中IKK-α mRNA的表达高于非活动组SLE患者(P<0.01).②SLE患者IFN-αmRNA的表达低于对照组(P<0.01),IFN-α mRNA的表达在非活动组SLE患者中低于活动组SLE患者(P<0.01).③SLE患者血清中IFN-α的水平高于对照组(P<0.01),其中,活动组SLE患者血浆IFN-α水平显著高于非活动组患者(P<0.05);SLE患者血浆中IFN-α浓度与抗双链DNA(dsDNA)抗体呈正相关(P=0.001),与补体C3水平呈负相关(P=0.005).④SLE患者IKK-α mRNA的表达与血浆中IFN-α的水平呈正相关(P=0.001).结论 SLE患者IKK-α mRNA的表达明显增高,且与血浆中IFN-α的水平呈正相关;而血浆中IFN-α的水平与SLE的发病及病情活动相关,提示IKK-α可能在SLE的发病中发挥重要的作用.     

系统性红斑狼疮患者血浆单核细胞化学吸引蛋白-1检测及其临床意义

目的 分析血浆单核细胞化学吸引蛋白-1(MCP-1)水平与系统性红斑狼疮(SLE)脏器受累及病情严重性的关系,探讨检测血浆MCP-1水平的临床意义.方法 采用酶联免疫吸附试验(ELISA)法检测95例SLE患者血浆MCP-1水平,并与21名健康体检者对照.结果 血浆MCP-1水平在SLE患者为(849±289)pg/ml,显著高于健康对照组的(426±266)pg/ml(P<0.01);在SLE患者,血浆MCP-1水平在有狼疮肾炎(LN)者明显高于无LN患者(P<0.01),并发狼疮脑病的患者也明显高于无中枢神经系统损害的患者(P相似文献   

Elevated levels of soluble fractalkine in active systemic lupus erythematosus: potential involvement in neuropsychiatric manifestations

OBJECTIVE: To determine levels of the soluble form of the chemokine fractalkine (sFkn) and its receptor, CX(3)CR1, in patients with systemic lupus erythematosus (SLE) with neuropsychiatric involvement (NPSLE) and in SLE patients without neuropsychiatric involvement, and to assess their relationship with disease activity and organ damage. METHODS: Levels of sFkn in serum and cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay. Expression of Fkn and CX(3)CR1 was quantified using real-time polymerase chain reaction. Surface expression of CX(3)CR1 on peripheral blood mononuclear cells (PBMCs) was determined by flow cytometry. Disease activity and organ damage were assessed using the SLE Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index, respectively. RESULTS: Serum sFkn levels were significantly higher in patients with SLE than in patients with rheumatoid arthritis (RA) or healthy controls. In addition, significant correlations between serum sFkn levels and the SLEDAI, the SLICC/ACR Damage Index, anti-double-stranded DNA and anti-Sm antibody titers, immune complex levels (C1q), and serum complement levels (CH50) were observed. Expression of CX(3)CR1 was significantly greater in PBMCs from patients with active SLE than in those from RA patients or healthy controls. Levels of sFkn were also significantly higher in CSF from untreated patients with newly diagnosed NPSLE than in SLE patients without neuropsychiatric involvement; treatment reduced both serum and CSF levels of sFkn in patients with SLE. CONCLUSION: Soluble Fkn and CX(3)CR1 may play key roles in the pathogenesis of SLE, including the neuropsychiatric involvement. Soluble Fkn is also a serologic marker of disease activity and organ damage in patients with SLE, and its measurement in CSF may be useful for the diagnosis of NPSLE and followup of patients with NPSLE.     

Dysregulated expression of CXCR4/CXCL12 in subsets of patients with systemic lupus erythematosus

Objective

CXCR4 is a chemokine with multiple effects on the immune system. In murine lupus models, we demonstrated that monocytes, neutrophils, and B cells overexpressed CXCR4 and that its ligand, CXCL12, was up‐regulated in diseased kidneys. We undertook this study to determine whether CXCR4 expression was increased in peripheral blood leukocytes from patients with systemic lupus erythematosus (SLE) and whether CXCL12 expression was increased in kidneys from patients with SLE.

Methods

Peripheral blood leukocytes from 31 SLE patients, 8 normal controls, and 9 patients with rheumatoid arthritis were prospectively analyzed by flow cytometry for CXCR4 expression. Biopsy samples (n = 14) from patients with lupus nephritis (LN) were immunostained with anti‐CXCL12 antibody.

Results

CD19+ B cells and CD4+ T cells from SLE patients displayed a >2‐fold increase (P = 0.0001) and >3‐fold increase (P < 0.0001), respectively, in median CXCR4 expression compared with that in controls (n = 7–8). Moreover, CXCR4 expression on B cells was 1.61‐fold higher in patients with SLE Disease Activity Index (SLEDAI) scores >10 (n = 8) than in patients with SLEDAI scores ≤10 (n = 16) (P = 0.0008), 1.71‐fold higher in patients with class IV LN (n = 5) than in patients with other classes of LN (n = 7) (P = 0.02), and 1.40‐fold higher in patients with active neuropsychiatric SLE (NPSLE) (n = 6) than in patients with inactive NPSLE (n = 18) (P = 0.01). CXCL12 was significantly up‐regulated in the tubules and glomeruli of kidneys in patients with LN (n = 14), with the percentage of positive cells correlating positively with the severity of LN.

Conclusion

CXCR4 appears to be up‐regulated in multiple leukocyte subsets in SLE patients. The heightened expression of CXCR4 on B cells in active NPSLE and of CXCL12 in nephritic kidneys suggests that the CXCR4/CXCL12 axis might be a potential therapeutic target for SLE patients with kidney and/or central nervous system involvement.

     

Elevation of serum CXCL13 in SLE as well as in sepsis

Recent studies have demonstrated that CXCL13 serum levels correlate significantly with systemic lupus erythematosus (SLE) disease activity. However, experimental studies show that CXCL13 production can also be induced by bacterial exposure as well as in response to inflammatory cytokines. This report asks whether CXCL13 serum levels are elevated in patients with evidence of bacterial infections and whether there is a correlation with the C-reactive protein (CRP) levels or the severity of illness in critically ill patients. CXCL13 levels were compared in 39 patients with active SLE (without concomitant infection), 40 non-SLE patients with sepsis, and 40 healthy controls by enzyme-linked immunosorbent assay (ELISA) methodology. We also tested storage conditions and freeze-thaw cycles for stability of CXCL13 in serum samples. Our studies demonstrated that the median CXCL13 serum levels were significantly elevated in patients with SLE [median 83?pg/ml (interquartile range 38-366)] or sepsis [359?pg/ml (151-459)] compared with healthy controls [32?pg/ml (27-41), p?相似文献   

系统性红斑狼疮患者血浆骨桥蛋白水平与疾病活动性及脏器损害的相关性研究

目的 检测系统性红斑狼疮(SLE)患者血浆中骨桥蛋白(OPN)的水平,分析其与SLE活动性及脏器损害间的关系.方法 选择68例SLE患者和36名健康体检者,采用酶联免疫吸附试验(ELISA)检测其血浆中的OPN水平.记录采血时患者的系统性红斑狼疮疾病活动指数(SLEDAI)、实验室指标等.结果 SLE患者OPN血浆水平明显高于正常对照组[(4.5±2.0)ng/ml与(1.6±0.7)ng/ml,P＜0.01 ].SLE疾病活动组高于非活动组[(5.3±2.0)ng/ml与(3.4±1.3)ng/ml,P＜0.01];SLE患者伴有肾脏损害组高于无肾脏损害组[(5.8±2.1)ng/ml与(3.5±1.3)ng/ml,P＜0.01],有肺间质病变、胃肠道病变和心包炎的高于无脏器损害[(4.8±1.2)、(6.3±1.4)、(5.4±2.6)ng/ml与(3.5+1.3)ng/ml,P＜0.05],抗心磷脂抗体阳性患者OPN水平高于抗心磷脂抗体阴性患者[(5.3±2.4)ng/ml与(4.2±1.7)ng/ml,P＜0.05].OPN血浆水平与SLEDAI呈正相关(r=0.523,P＜0.01),与尿蛋白定量(24 h)呈正相关r=0.403,P=0.001),与补体C3呈负相关r=-0.398,P=0.001),与红细胞沉降率(ESR)、抗dsDNA抗体、抗Sm抗体、IgG、IgA、IgM、球蛋白及关节炎等无相关性(P＞0.05) .结论 OPN可能参与SLE的发病,临床上可作为疾病活动及脏器损伤的观察指标.     

Abnormal expression of chemokine receptors on T-cells from patients with systemic lupus erythematosus

The expression of chemokine receptors on T-cells and chemokine levels in the blood was studied in 23 patients with SLE (ACR criteria), seven patients with rheumatoid arthritis (RA) and in 15 healthy controls using flow cytometry, RT-PCR and ELISA. The cell surface expression of the chemokine receptors CXCR5 and CCR6 was decreased in SLE patients compared with controls (P = 0.051 and P = 0.002, respectively). The decrease of CXCR5 was confined to SLE patients with inactive disease (SLEDAI < 6) compared with active disease (SLEDAI > 6) and controls. CXCR2 and CCR1 were increased in patients with active SLE compared with patients with inactive disease (P = 0.001 and P = 0.01, respectively) and with controls (P = 0.02 and P = 0.053, respectively). The levels of the chemokines MIP-1alpha MCP-1, SDF-1alpha, IP-10 and RANTES were significantly elevated in SLE patients compared with controls. Patients with renal involvement had increased surface expression of CXCR3 and CCR3 (P = 0.04 in both) and a lower level of soluble IP-10 compared with patients without renal disease (P = 0.025) and compared with controls (P = 0.001). The ratio between CCR5 and CCR3 was significantly increased in RA patients compared with SLE patients and controls supporting a Th1 overweight in RA. In conclusion, patients with SLE showed abnormal T-cell expression of several chemokine receptors and levels of soluble chemokines in their plasma/serum.     

Adrenomedullin--a potential disease activity marker and suppressor of nephritis activity in systemic lupus erythematosus

OBJECTIVES: To investigate whether plasma adrenomedullin (AM) level is elevated in lupus nephritis and to examine if plasma AM level is correlated with systemic lupus erythematosus (SLE) disease activity and severity of lupus nephritis after multivariate adjustment. METHODS: Consecutive SLE patients and healthy volunteers of age >/=16 were recruited from the rheumatology clinics of two hospitals in Hong Kong. SLE patients with nephritis fulfilled the American College of Rheumatology criteria for renal involvement and had percutaneous renal biopsy performed. Subjects were divided into three groups: (i) SLE patients with nephritis, (ii) SLE patients without nephritis and (iii) normal controls. The demographic and clinical variables were compared between these groups of patients and plasma AM level was determined by radioimmunoassay. Factors associated with plasma AM level were explored by regression analysis with adjustment of confounding factors. RESULTS: Sixty SLE patients (39 with nephritis and 21 without) and 23 normal subjects were studied. The plasma AM level of SLE patients was significantly higher than that of normal controls. SLE patients with nephritis had significantly higher plasma AM level than those without nephritis and normal controls (P<0.001). In regression analysis, proteinuria was negatively associated with plasma AM level (P=0.006) whereas SLE disease activity index was positively associated with plasma AM level after multivariate adjustment (P=0.002). CONCLUSIONS: Plasma AM is elevated in lupus nephritis, which correlates with lupus disease activity. It is negatively associated with urine protein excretion although it is unrelated to the type of renal pathology per se. Plasma AM may play a role to suppress the activity of lupus nephritis.     

Association of chemokine CXCL12-3'G801A polymorphism with systemic lupus erythematosus in a Han Chinese population

CXCL12, also known as stromal cell-derived factor (SDF-1), is a CXC chemokine. Recent reports have shown that CXCL12 might play key roles in a murine model of lupus and in patients with systemic lupus erythematosus (SLE). A common variant at position 801 in 3'-untranslated region in CXCL12 gene (designated CXCL12-3'G801A) has been reported in association with autoimmune diseases, such as type 1 diabetes and systemic sclerosis. We investigated the influence of CXCL12-3'G801A polymorphism on susceptibility to SLE by genotyping this single nucleotide polymorphism in 422 SLE patients and 374 healthy controls. The frequency of G/G homozygote was observed in 60.0% of SLE patients and in 52.7% of healthy individuals (χ(2?)=?4.275, p?=?0.039). Compared with patients with G/A and A/A genotype, SLE patients with G/G genotype were also more prone to developing photosensitivity (χ(2?)=?6.778, p?=?0.034), renal damage (χ(2?)=?6.388, p?=?0.041) and to producing antibodies against nucleosomes (χ(2?)=?8.341, p?=?0.015). Moreover, the plasma level of CXCL12α was also significantly increased in patients with G/G homozygote than in healthy controls carrying the same genotype [(4067.0?±?1092.3) pg/ml vs. (3278.5?±?547.4) pg/ml, p?=?0.002]. Our results suggest that polymorphism in CXCL12-3'G801A might be a genetic risk factor for developing SLE. The association of G/G homozygote with nephritis and skin damage developed in SLE patients might be due to its effects upon the production of auto-antibodies and CXCL12 protein.