TNF检测在环磷酰胺治疗狼疮性肾炎中的价值

目的 探讨肿瘤坏死因子（ＴＮＦ）检测在大剂量环磷酰胺静脉冲击治疗狼疮性肾炎（ＬＮ）中的价值。方法 用ＥＬＩＳＡ双抗体夹心法检测５１例ＬＮ患者环磷酰胺静脉冲击治疗（ＩＶ－ＣＴＸ）前后血清和尿ＴＮＦ水平。结果 活动期ＬＮ患者血清和尿ＴＮＦ水平显著高于稳定性（Ｐ〈０．００１）。血甭ＴＮＦ水平与血沉呈显著正相关（ｎ＝５１,ｒ＝０．３８６,Ｐ〈０．０５）。轻度肾功不全患者血清ＴＮＦ显著高于肾功正常（Ｐ,０．     

外周血单个核细胞在狼疮性肾炎病人体内高效表达…

为了确定狼疮性肾炎（ＬＮ）病人体内是否存在内源性ＩＬ－６表达增高及其来源，作者应用ＥＬＩＳＡ法检测５８例ＬＮ病人的血清及外周血单个核细胞（ＰＢＭＣ）内ＩＬ－６蛋白含量，用原位杂交方法结合ＩＢＡ２．０图像分析系统，检测其中２０例ＬＮ病人ＰＢＭＣ在未受任何刺激时ＩＬ－６ｍＲＮＡ表达强度，并分析三者之间的关系，结果表明该三者水平在ＬＮ病人体内均异常增高，活动期尤其明显，三者之间互呈直线正相关，提示ＬＮ病     

环磷酰胺冲击疗法对狼疮性肾炎血清IL—6的影响

目的探讨白介素-6(IL-6)在狼疮性肾炎(LN)发病中的作用及大剂量环磷酰胺静脉给药(IV-CTX)对IL-6产生的影响.方法应用ELISA双抗体夹心法对IV-CTX治疗前后LN患者血清IL-6水平进行检测.结果活动期LN血清IL-6水平显著高于非活动期及健康人(P＜0.001),血清IL-6水平与血沉呈显著正相关(n=22,r=0.570,P＜0.01);抗ds-DNA抗体阳性且血清IgG＞16g/L的LN患者有更高的血清IL-6水平(P＜0.05);活动期LN治疗4w后血清IL-6水平显著下降(P＜0.001).结论LN的B细胞过度活化和自身抗体产生可能与IL-6分泌过量有关.IV-CTX可能通过抑制IL-6的产生而减轻免疫损伤,血清IL-6检测有助于监视狼疮活动和免疫抑制剂疗效.     

白细胞介素17 在狼疮性肾炎小鼠中的表达及抗白细胞介素17抗体的干预作用

 目的:探讨白细胞介素17（IL-17）在狼疮性肾炎(LN）小鼠中的表达及抗IL-17抗体的干预作用。方法:11周龄的雌性MRL/lpr小鼠36只随机分为实验组和干预组,另有同龄雌性昆明小鼠18只为对照组。干预组每只小鼠腹腔注射抗小鼠IL-17多克隆抗体20 μg,每2周1次,至实验观察点结束。各组分别于第1次给药后的24 h、14 d及28 d处死6只小鼠。光镜下观察肾脏病理情况,ELISA法检测小鼠血清IL-17的含量,免疫组化法检测肾组织IL-17的表达水平。结果:MRL/lpr小鼠肾小球系膜细胞及基质弥漫增生,肾小管上皮细胞颗粒及空泡变性,灶状萎缩,肾间质淋巴及单核细胞浸润伴纤维化;而干预组肾脏病理改变较实验组为轻。MRL/lpr小鼠的血清IL-17含量在实验组各时点均显著高于对照组（P<0.05）,而在干预组各时点均显著低于实验组（P<0.05）。IL-17在实验组小鼠肾小管上皮细胞中的表达明显增强,在各时点均显著高于对照组（P<0.05）;在干预组,IL-17在各时点的表达均显著低于实验组（P<0.05）。结论:IL-17在MRL/lpr小鼠血清与肾组织中的表达显著增加,而抗IL-17抗体可通过抑制IL-17的表达而抑制LN的炎症免疫反应,减轻肾脏病理损害。     

Th17/Treg在早期判断狼疮性肾炎治疗反应中的应用价值

目的:了解外周血辅助性T细胞(helper T cell,Th)17 /调节性T细胞(regulatory T cells,Treg)和相关细胞因子在狼疮性肾炎(lupus nephritis,LN)治疗前后的变化和意义,并评估Th17/Treg在预测LN治疗反应中的价值。方法:选取2016年2月至2018年10月于复...     

白细胞介素—1受体拮抗剂基因多态性与狼疮性肾炎临床病…

白细胞介素－１受体拮抗剂（ＩＬ－１ｒａ）基因多态性被认为与血浆ＩＬ－１ｒａ浓度有关，为探讨ＩＬ－１ｒａ基因多态性与狼疮性肾炎（ＬＮ）之间的关系，应用ＰＣＲ方法对９８例ＬＮ患者和９８名正常人的ＩＬ－１ＲＡ基因多态性的分布进行了观察，并结合临床病理特点和随访资料进行了分析。结果：（１）ＬＮ患者与正常对照组ＩＬ１ＲＮ＾＊２等位基因携带率无统计学差异（Ｐ〉０．０５）；（２）ＬＮ患者携带ＩＬ１ ＲＮ＾＊２者     

慢性肾炎患者血清sIL—2R和IL—8的变化及意义

本研究用ＥＬＩＳＡ双抗体夹心法对慢性肾炎肾功能不全各期患者血清ｓＩＬ－２Ｒ和ＩＬ－８水平进行了测定。结果显示：（１）肾功能不全代偿期ｓＩＬ－２Ｒ水平显著高于健康人，提示此期存在Ｔ细胞异常活化。（２）氮质血症期ｓＩＬ－２Ｒ水平显著高于健康人和代偿期，与Ｓｃｒ呈显著正相关提示血清ｓＩＬ－２Ｒ水平可作为肾小球肾炎恶化的重要指标。     

红细胞白介素—8受体研究进展

ＩＬ－８是很强的中性粒细胞调节因子，它具有趋化、激活中性粒细胞等作用，与急、慢性炎症有密切关系。许多细胞经细胞因子（ＩＬ－１的ＴＮＦ）或脂多糖（ＬＰＳ）刺激后释放ＩＬ－８。中性粒细胞、单核细胞上有ＩＬ－８受体已为人所知，近来发现红细胞上也存在大ＩＬ－８受体，该受体能将全血中的ＩＬ－８等趋化因子迅速地从血浆中清除掉，它在调节炎症过程中以及疟疾发展上都发挥着重要作用。本文概述了红细胞ＩＬ－８受体的基因     

抗核抗体系列检测对狼疮性肾炎进行鉴别诊断的临床意义

目的探讨抗核抗体(ANA)系列指标在狼疮性肾炎(LN)患者中的表达情况及临床意义.方法对406例系统性红斑狼疮(SLE)患者(其中LN 122例)和74例其他自身免疫病患者及120例健康体检者采用间接免疫荧光法测定ANA,应用欧蒙印迹法测定ANA系列.结果 SLE患者ANA阳性率为94.49%,其他自身免疫病组ANA阳...     

Clinical and functional consequences of anti-properdin autoantibodies in patients with lupus nephritis

Properdin is the only positive regulator of the complement system. In this study, we characterize the prevalence, functional consequences and disease associations of autoantibodies against properdin in a cohort of patients with autoimmune disease systemic lupus erythematosus (SLE) suffering from lupus nephritis (LN). We detected autoantibodies against properdin in plasma of 22·5% of the LN patients (16 of 71) by enzyme-linked immunosorbent assay (ELISA). The binding of these autoantibodies to properdin was dose-dependent and was validated by surface plasmon resonance. Higher levels of anti-properdin were related to high levels of anti-dsDNA and anti-nuclear antibodies and low concentrations of C3 and C4 in patients, and also with histological signs of LN activity and chronicity. The high negative predictive value (NPV) of anti-properdin and anti-dsDNA combination suggested that patients who are negative for both anti-properdin and anti-dsDNA will not have severe nephritis. Immunoglobulin G from anti-properdin-positive patients’ plasma increased the C3b deposition on late apoptotic cells by flow cytometry. Nevertheless, these IgGs did not modify substantially the binding of properdin to C3b, the C3 convertase C3bBb and the pro-convertase C3bB, evaluated by surface plasmon resonance. In conclusion, anti-properdin autoantibodies exist in LN patients. They have weak but relevant functional consequences, which could have pathological significance.     

Important considerations in pregnant patients with lupus nephritis

Introduction: In the last few decades, identification of predictors of pregnancy outcome and appropriate pregnancy planning have significantly reduced the maternal and fetal risks in pregnant women with lupus nephritis.

Areas covered: Successful pregnancies have been reported even in women with chronic renal disease and renal insufficiency. However, refractory hypertension and severe renal or cardiac chronic dysfunction are still considered contraindications to pregnancy. Pre-term delivery and fetal growth restriction may still occur in SLE patients more frequently than in healthy women, even in pregnancies regularly planned and monitored by a team of nephrologists and gynaecologists.

Expert commentary: Stable disease remission is the most important factor for a successful pregnancy. In case of flare-ups of lupus, timely diagnosis and appropriate management may ensure a successful outcome in the majority of pregnant women. The negative role of anti-phospholipid antibodies and of chronic arterial hypertension may be countered with appropriate anticoagulation and anti-hypertensive therapy. Further studies are needed to better assess the possible impact of pregnancy on the long-term outcome of lupus nephritis.     

Up-regulation of IL-18 and predominance of a Th1 immune response is a hallmark of lupus nephritis

There is evidence that nephritis is dominated by a Th1 immune response in systemic lupus erythematosus. Since IL-18 promotes polarization of the immune response toward Th1, we investigated the role of this cytokine in lupus nephritis (LN). A total of 133 lupus patients and 44 healthy subjects were enrolled. Demographic and clinical characteristics with renal biopsy data were recorded. IL-18 along with IFN-gamma and IL-4, two prototypical of Th1 and Th2 cytokines, were measured in serum by ELISA. Peripheral blood lymphocytes were analysed by flow cytometry for IFN-gamma and IL-4. IL-18 expression was determined by immunohistochemistry in 13 renal biopsy specimens from patients with LN and 2 controls. Serum IL-18 was higher in lupus patients than in controls. Levels of IL-18 correlated with urinary microalbumin and were increased in patients with LN when compared to those without LN. IL-18 expression was also increased within the glomeruli of nephritic patients and was primarily detected within the mesangial matrix and in infiltrating mononuclear cells. Measurement of IFN-gamma and IL-4 in either sera or peripheral blood lymphocytes showed high IFN-gamma along with low IL-4 expression in LN patients compared to patients without nephritis. A positive correlation between serum IL-18 and IFN-gamma levels was found. IL-18 may play a prominent role in the pathogenesis of LN by promoting a cytokine imbalance towards a Th1 immune response. Measurement of IL-18 may be helpful for the early identification of lupus patients with LN and may help gauge the response to treatment in patients with active LN undergoing treatment.     

白细胞介素-15在狼疮性肾炎活动病变中的临床意义

目的：检测狼疮肾炎(LN)患者外周血白细胞介素15（IL-15）水平，并进一步分析其与临床有关指标的关系及治疗前后的变化。方法：用酶联免疫吸附法（ELISA）方法检测外周血IL-15水平；采用梯度密度离心法分离外周血单个核细胞(PBMCs)；并研究地塞米松对体外培养的活动期LN患者PBMCs分泌IL-15、IgG和dsDNA抗体的影响。结果：（1）LN组患者血清IL-15水平显著高于正常对照组(P<0.01)，活动期LN患者血清IL-15水平显著高于缓解期患者(P<0.05)。（2）活动期LN患者血清IL-15水平与SLE活动性指数(SLEDAI)、抗dsDNA抗体、24 h尿蛋白排泄量呈正相关关系，与补体C3呈负相关关系，而与血肌酐无相关关系。（3）激素联合环磷酰胺系统治疗活动期LN患者12周，治疗后随病情缓解血清IL-15水平明显下降。（4）体外培养的活动期LN患者PBMCs分泌IL-15、IgG、dsDNA抗体均显著高于正常对照组，而且IL-15分泌与dsDNA抗体和IgG合成呈正相关关系；地塞米松可明显抑制活动期LN患者PBMCs合成IL-15、IgG、dsDNA抗体。结论：LN患者外周血IL-15水平显著增高,IL-15可能参与LN的病理生理过程；血清IL-15水平检测可作为判断LN是否活动的指标之一。     

雌激素刺激活动性狼疮肾炎外周血单个核细胞的IL-10表达

探讨性激素对活动性狼疮肾炎外周血单个核细胞 (PBMC)Th2细胞活化的影响。采用ELISA、RT PCR等方法检测了雌激素对 19例活动性狼疮肾炎和 16例健康人外周血单个核细胞 (PBMC)IL 10表达的调节作用。活动期狼疮肾炎PBMCIL 10mRNA和蛋白含量明显高于正常人 (P <0 0 5 ) ;与正常对照相比 ,雌激素明显提高了活动性狼疮肾炎PBMCIL 10蛋白和mRNA水平 (P <0 0 5 ) ,雄激素的加入明显抑制了雌激素诱导的活动性狼疮肾炎PBMCIL 10蛋白和mRNA水平 (P <0 0 5 )。雌激素、雄激素比例失调可能参与了活动性狼疮肾炎IL 10的高效表达     

Treatment of systemic lupus erythematosus in two patients with extreme B-cell lymphopenia: importance of immunomonitoring and avoidance of B-cell targeted therapy

Introduction:?Because dysfunction of the B-cell compartment is thought to be important in the pathogenesis of systemic lupus erythematosus (SLE), there has been a recent focus on therapies that target humoral immunity via multiple mechanisms. The aim of this paper was to demonstrate the importance of immunomonitoring in two cases with class II lupus nephritis on steroids who presented with a flare-up of disease. After a thorough work-up for infectious triggers of disease activity, conversion to another histopathological class of lupus nephritis was suspected. Deterioration of the patients’ clinical condition made kidney biopsy impossible, and as B-cell targeted therapy was considered, we decided to perform an immunophenotypic analysis and to tailor therapy to the results of the lymphocyte profile. As we incidentally found extremely low B-cell counts, any B-cell–targeted therapy was prohibited, and cyclophosphamide (Cy) was considered a viable therapeutic option.

Methods:?We performed flow-cytometric lymphocyte (Ly) phenotyping (CD19, CD3, CD3CD4, CD3CD8, CD56/16) on two patients with class II lupus nephritis before and after two intravenous (i.v.) Cy pulse administrations. During all this time, patients were on steroids.

Results:?Both patients showed extreme B-cell lymphopenia, a marker of active SLE, which was not greatly impacted by the treatment over the follow-up period.

Conclusions:?As current therapies are aimed at targeting the B cell, an important component of adaptive immunity, caution must be exercised before their use. In addition, monitoring of Ly subsets is essential due to the occurrence of extreme B-cell lymphopenia.     

抗核抗体系列及补体检测对狼疮性肾炎的诊断意义

目的 探讨抗核抗体系列及补体检测对系统性红斑狼疮(SLE)伴狼疮性肾炎(LN)诊断的意义.方法 对1 699例SLE患者和120例健康体检者采用间接免疫荧光法测定抗核抗体(ANA),应用欧蒙印迹法测定抗核抗体系列,应用散射比浊法测定补体C3、C4.结果 1699例SLE患者,LN组921例,ANA阳性率为97.4％;不伴LN组778例,ANA阳性率为98.2％;与对照组比较,r=0.983,P=0.001,差异有统计学意义.LN组的抗组蛋白抗体,抗核小体抗体,抗双链DNA抗体阳性率分别为49.3％、59.8％、63.3％;不伴LN组分别为21.5％、35％、47.9％;差异有统计学意义(r=0.452,P=0.007).抗线粒体-2抗体和抗着丝点抗体阳性率,LN组与不伴肾炎组比较差异有统计学意义(r=0.291,P=0.015).当抗组蛋白抗体+抗核小体抗体+抗双链DNA抗体同时阳性时,LN患者其补体C3,C4水平比这三种抗体非同时阳性时的水平均更低,差异有统计学意义(r=0.583,P=0.009).结论 抗核抗体系列及补体的血清学检测对诊断LN及其预后判断、疗效观察等具有重要意义.     

Association of miRNA-145 expression in vascular smooth muscle cells with vascular damages in patients with lupus nephritis

miRNAs have been found to contribute to the regulation of multiple cellular processes, including cell apoptosis, differentiation and proliferation. The patients with lupus nephritis (LN) exhibit thickened renal vascular membrane and highly proliferative vascular smooth muscle cells (VSMCs). Of various miRNAs discovered, miR-145 is essential to mediate the proliferation of VSMCs and the formation of atherosclerotic plaques. In this study, we studied the pathological and vascular damage of renal LN, and the correlation between miR-145 expression in VSMCs and the vascular damages. Serum, urine, and renal biopsies were obtained from 41 patients with active LN. The serum and urinary VEGF levels were examined to confirm the renal damage of each patient. Biopsies were stained to observe the glomerular segmental lesions, sclerosis, and to evaluate the vascular damages. The expression of miR-145 was also examined to determine the correlation between its expression and the vascular damages. The expression of miR-145 was mainly detected in the renal VSMCs and the epithelial cells of glomerular proximal convoluted tubule. Nevertheless, the expression of miR-145 reduced as the tunicae media vasorum ratios increased, indicating the development of LN inhibits the expression of miR-145. Furthermore, our studies revealed no significant correlation among renal interstitial vascular damage, glomerular damage and severity classification of LN. Therefore, we suggest the damage of renal interstitial vascular should be considered as one of the factors to evaluate the severity of the LN.