狼疮性肾炎治疗的研究进展

近年来细胞毒类药物、生物制剂、基因工程、骨髓干细胞移植及其它治疗LN药物和方法的研究取得较大进展，以致对LN的疗效进一步提高。     

FEN1基因突变在狼疮性肾炎发病机制中的作用

目的 探讨FEN1基因突变在狼疮性肾炎(Lupus nephritis,LN)患者发病机制中的作用.方法 收集43例LN患者和26例健康者的外周血标本,采用全血基因组DNA柱式试剂盒提取DNA,直接PCR方法扩增FEN1基因片段,扩增后PCR产物应用基因测序方法检测FEN1基因序列,并对测序结果与基因数据库中FEN1基因进行比较,搜索可能的突变位点.chi-square检验比较LN患者及健康者FEN1基因突变情况.结果 LN患者正向测序中存在946位碱基C缺失突变(p=0.046).结论 LN患者FEN1基因存在946位碱基C缺失突变.     

狼疮性肾炎发病机制研究进展

系统性红斑狼疮是一种原因不明的多器官炎症的自身免疫病，其重要特征是Ｔ和Ｂ淋巴细胞对自身核抗原的耐受性丧失，出现多种抗核抗原成分的自身抗体，特别是ＩｇＧ型抗－ＤＮＡ抗体，在狼疮性肾炎发病机制中有重要的地位。近年来，动物模型及人类系统性红斑狼疮研究表明，本病具有复杂的多基因遗传特性，主要组织相容性复合物和非组织相性复合物基因决定了本病的易感性，尤其是自身抗体的产生。凋亡为自身抗体的产生提供了可能的抗原     

狼疮性肾炎治疗的研究进展

近年来细胞毒类药物、生物制剂、基因工程、骨髓干细胞移植及其它治疗LN药物和方法的研究取得较大进展 ,以致对LN的疗效进一步提高     

狼疮性肾炎发病机制研究进展

系统性红斑狼疮是一种原因不明的多器官炎症的自身免疫病，其重要特征是Ｔ和Ｂ淋巴细胞对自身核抗原的耐受性丧失，出现多种抗核抗原成分的自身抗体，特别是ＩｇＧ 型抗－ ＤＮＡ 抗体，在狼疮性肾炎发病机制中有重要的地位。近年来，动物模型及人类系统性红斑狼疮研究表明，本病具有复杂的多基因遗传特性，主要组织相容性复合物和非组织相容性复合物基因决定了本病的易感性，尤其是自身抗体的产生。凋亡为自身抗体的产生提供了可能的抗原。阳离子抗－ ＤＮＡ抗体在介导狼疮性肾炎中发挥了重要的作用。     

狼疮性肾炎的生物标志物研究进展

敏感和特异的生物标志物在判断狼疮性肾炎(LN)活动性和严重性、预测其发作、监测治疗效果方面具有重要临床意义,近年在LN生物标志物研究中已有一些新发现,可能对LN非侵入性诊断和预后判断提供帮助,但目前尚未能替代传统的临床指标,并仍需大规模多中心前瞻性纵向队列研究进一步明确和论证.     

狼疮性肾炎的治疗新进展

目前对狼疮性肾炎的治疗已经开展了很多临床试验,然而直到现在没有那种药物可以单独成为治疗LN的新标准方案。对这些前瞻性和回顾性研究进行整合分析,注意到这些研究的局限性,提出更合理的治疗LN研究方案。在临床工作中要根据每例患者的临床表现、疾病的活动水平、病理改变、药物耐受程度、自愿度和前期治疗等进行个体化治疗是非常重要的。     

阻断协同刺激信号转导治疗狼疮性肾炎的实验研究进展

近年研究表明，两条主要的协同刺激信号转导途径：CD28、CTLA-4／B7、CD40／CD40L在狼疮性肾炎的发生发展中起着重要的作用，阻断协同刺激信号转导治疗狼疮性肾炎在动物实验中取得了明显的效果，有可能为临床治疗狼疮性肾炎提供新的方法。     

阻断协同刺激信号转导治疗狼疮性肾炎的实验研究进展

近年研究表明 ,两条主要的协同刺激信号转导途径 :CD2 8、CTLA -4 /B7、CD40 /CD40L在狼疮性肾炎的发生发展中起着重要的作用 ,阻断协同刺激信号转导治疗狼疮性肾炎在动物实验中取得了明显的效果 ,有可能为临床治疗狼疮性肾炎提供新的方法     

狼疮性肾炎的病因与诊断研究进展

狼疮性肾炎(LN)是系统性红斑猿疮(SLE)患者最严重的并发症和死亡的主要原因之一,确切病因至今尚未明确,但遗传缺陷、环境危险因子、性激素异常等三大因素是SLE、LN的主要发病因素.肾脏病变程度与SLE的预后密切相关.狼疮性肾炎的病理分型是临床诊治及预后判断的基础.     

Treatment of lupus nephritis

Patients with lupus nephritis pose a therapeutic challenge and stimulate investigation of innovative treatment strategies. Although patient survival and renal function outcomes have improved over the last 4 decades, contemporary immunosuppressive regimens are not consistently effective and often require extended courses associated with insidious toxicities. Several strategies are under investigation to induce remissions more rapidly and to reduce the risk of long courses of cytotoxic drug therapy. The combination of pulse methylprednisolone and pulse cyclophosphamide may be more effective than pulse cyclophosphamide alone for patients with relatively severe proliferative lupus nephritis. Ongoing clinical studies evaluate the risk/benefit of other intensive induction regimens (eg, combination fludarabine with relatively low-dose pulse cyclophosphamide). A particularly vigorous strategy employs immunoablative cyclophosphamide with or without stem cell rescue. Several studies of sequential immunosuppressive therapy are in progress. It is anticipated that long-term toxicities can be lessened by substituting various maintenance agents (eg, azathioprine or mycophenolate mofetil) after initial cyclophosphamide therapy has induced a renal response. Additional information is needed to determine the role of this strategy. Furthermore, a number of standard and experimental immunosuppressive regimens (that do not include cyclophosphamide) are under investigation as well. Innovative approaches (eg, costimulatory blockade) offer the hope of more effective treatments without the risks of contemporary regimens.     

人类白细胞抗原DR基因与狼疮性肾炎相关性的探讨

目的 从基因水平探讨人类白细胞DR抗原(HLA-DR)基因与中国北方汉人狼疮性肾炎(LN)的相关性。方法 采用特异性引物-聚合酶链式反应(PCR-SSP)方法,检测89例系统性红斑狼疮(SLE)患者及106例健康者HLA-DRB1基因类型,进行临床相关性分析。结果 SLE患者的HLA-DR2及DR9基因频率明显高于对照组(0.36/0.20,RR=2.36,P<0.001;0.27/0.18,RR=1.69,P<0.05);DR2及DR9同时阳性的35例患者中,LN的发病率明显高于其它患者(RR=4.93,P<0.005),而且抗dsDNA抗体的阳性率也较高(RR=2.66,P<0.05)。结论 中国汉人HLA-DR2及DR9基因可能与SLE的遗传易感性有关,两者有相加作用,DR2及DR9同时阳性的SLE患者易患LN。     

Good response of membranous lupus nephritis to tacrolimus

A 22-year-old woman hospitalized for polyarthralgia was diagnosed with systemic lupus erythematosus (SLE). She was treated with prednisolone, and her clinical manifestations improved. However, she was re-admitted for renal biopsy because of persistent hypocomplementemia and development of proteinuria. The biopsy revealed segmental spike formation of basement membrane and subepithelial immune complex deposition, and membranous lupus nephritis (class V) was diagnosed. When tacrolimus was added to prednisolone, the serum complement titer quickly improved and proteinuria disappeared after about 11 months. Nevertheless, when tacrolimus was replaced examination showed cyclosporine due to gastrointestinal symptoms, she complained about arthralgia. Examination showed drop in the serum complement titer and recurrence of proteinuria. Renal biopsy at the time of recurrence showed increased subepithelial immune complex deposition in the capillary loops as compared to the first biopsy, a high degree of thickening of the basement membrane, and segmental circumferential interposition in some of the glomeruli. Membranous lupus nephritis (classes V + III) was diagnosed. By changing to tacrolimus and higher doses of steroids, the serum complement titer improved and proteinuria disappeared. This case indicates that tacrolimus can be an effective therapeutic agent for membranous lupus nephritis.     

Focal segmental lupus nephritis

Nineteen renal biopsies and one autopsy from fifteen patients with focal segmental lupus nephritis were examined by light and electron microscopy, and seven biopsies also by immunofluorescence microscopy. Histopathologic data were correlated with clinical course. Patients were selected on the basis of strict histologic criteria, and had to have a minimum of 2 years clinical follow-up after biopsy. All patients were treated with steroids. It could be demonstrated by light and electron microscopy that segmental lesions go through several stages of evolution, starting with mesangial proliferation, followed by necrosis and terminating as a nodule composed mainly of collagen. The necrotic lobule sometimes contains electron dense deposits, but no wire loop lesions. Prognosis was generally good with an average of 6.3 year survival of 86%. Factors contributing to outcome include number of involved glomeruli, amount of mesangial deposits outside the segmental lesions, and the presence of vasculitis. The pathogenesis of segmental lesions probably differs from that of diffuse lupus nephritis, constituting a localized reaction, independent of immune deposits in the remainder of the glomerulus, and with a considerable tendency to heal, particularly when treated with steroids.     

Hydralazine and lupus nephritis

Renal involvement is uncommon in the hydralazine induced systemic lupus erythematosus syndrome. Six women with hypertension are described who developed an immune complex glomerulonephritis after taking 50-300 mg hydralazine daily for 6 months to 7 years. Associated features were anemia (100%), hypocomplementemia (50%), a positive antinuclear antibody test (100%) and antibodies to double-stranded DNA (66%). All patients were slow acetylators and four had HLA-DR 4 genotype. Renal function deteriorated in all cases. Cessation of hydralazine combined with immunosuppressive therapy resulted in amelioration of the disease. It is likely that the patients had a hydralazine induced lupus glomerulonephritis, or alternatively had an unmasking of an inherent tendency to idiopathic lupus nephritis by hydralazine.