半乳糖缺陷型IgA1在IgA肾病中的研究进展

IgA肾病（IgA nephropathy,IgAN）是全球最常见的原发性肾小球肾炎并且可进展至终末期肾病,IgA1分子沉积在肾小球系膜是其区别于其他原发性肾小球肾炎的明显特征。近年来,IgAN在机制研究、基因组学、临床研究等方面取得了不错的进展,并发现半乳糖缺陷型IgA1（galactose deficient-Ig...     

IgA肾病

ＩｇＡ肾病在亚太地区为肾小环原发性疾病中发病率最高的疾病之一，本文通过对以往该病在病因、病机、病理、临床表现、实验室检查，治疗及预后等方面的文献进行总结归纳，使我们能更全面地了解该病，并指导我们对该病的诊断和治疗。     

尿半乳糖缺陷IgA1水平与IgA肾病严重程度的相关性

探讨IgA肾病（IgA nephropathy,IgAN）患者血清及尿液半乳糖缺陷IgA1（galactose-deficient IgA1,Gd-IgA1）水平与临床病理及肠黏膜屏障损伤指标的相关关系。酶联免疫吸附测定法检测血尿Gd-IgA1、炎性因子及肠黏膜屏障损伤指标水平。IgAN组45例,健康对照组25例。结果...     

外周血B淋巴细胞β1,3半乳糖基转移酶及其伴侣蛋白核酸表达和IgA肾病的关系

IgA肾病（IgAN）是全球范围内最常见的肾小球疾病,近期发现IgA1分子糖基化异常可能是其关键发病机制。IgAN患者外周血B细胞β1,3半乳糖基转移酶（β1,3GT）活性较健康人显著下降。β1,3GT具有特殊的蛋白伴侣Cosmc（核心Ⅰβ3-半乳糖基转移酶特异性分子伴侣）。本研究观察IgAN患者外周血B淋巴细胞核心β1,3GT基因C1GALT1和Cosmc表达水平,进一步了解其发病机制。     

IgA肾病患者扁桃体B1a细胞和IgA1阳性细胞表达及相关因素分析

目的 研究B1a和IgA1阳性细胞在IgA肾病患者扁桃体中的表达及B1a细胞与血尿、蛋白尿和病理Lee分级的关系。 方法 肾活检确诊为原发性IgA肾病及非肾炎慢性扁桃体炎患者各8例为对象,用免疫荧光法和激光共聚焦显微镜对其扁桃体组织进行B1a及IgA1细胞定位和定量计算,并按蛋白尿程度和Lee分级标准与IgA肾病组B1a细胞数量行统计学分析。 结果 B1a细胞主要分布在扁桃体生发中心和小结帽;IgA1细胞主要分布在上皮内、上皮下,以上皮和淋巴组织交界区为多。与慢性扁桃体炎组比较,IgA肾病组两种细胞表达明显增多（P < 0.01）,且呈正相关（r = 0.778,P = 0.023）。在血尿伴蛋白尿和Lee≥Ⅲ级组B1a细胞显著高于单纯血尿和Lee<Ⅲ级组（P < 0.05）。 结论 IgA肾病患者扁桃体中IgA1可能是B1a细胞分泌的。B1a细胞数量随着患者蛋白尿的出现和病理严重程度的加重而增加,可能在疾病发生和进展过程中起着重要的作用。     

尿半乳糖缺陷IgA1水平与IgA肾病严重程度的相关性

探讨IgA肾病(IgA nephropathy, IgAN)患者血清及尿液半乳糖缺陷IgA1(galactose-deficient IgA1, Gd-IgA1)水平与临床病理及肠黏膜屏障损伤指标的相关关系。酶联免疫吸附测定法检测血尿Gd-IgA1、炎性因子及肠黏膜屏障损伤指标水平。IgAN组45例, 健康对照组25例。结果显示IgAN组患者血清炎性因子肿瘤坏死因子α和白细胞介素6及血尿Gd-IgA1水平高于健康对照组人群(均P<0.05);Spearman秩相关分析结果显示尿Gd-IgA1水平与血肌酐、24 h尿蛋白量及肾脏损伤程度呈正相关(均P<0.05);IgAN组患者肠道黏膜屏障损伤指标细胞黏附分子1、D-乳酸、脂多糖、二胺氧化酶水平高于健康对照组人群(均P<0.05), 且与尿Gd-IgA1水平呈正相关(均P<0.05)。本研究结果提示尿Gd-IgA1水平与IgAN严重程度及肠道黏膜屏障损伤指标相关。     

肾移植术后IgA肾病复发

IgA肾病（IgAN）是常见的原发性肾小球肾炎之一,也是导致终末期肾病的重要危险因素。肾移植是IgAN导致的终末期肾病患者的首选治疗方式,但肾移植术后仍存在IgAN复发风险。目前有关肾移植术后IgAN复发的相关研究进展缓慢。IgAN复发的发病机制尚未明确,其病理表现不具备特异性,确诊仍依赖于肾活组织检查,且尚未见有效的复发性IgAN防治方案。本文主要从肾移植术后IgAN复发的发病机制、诊断、危险因素及治疗手段等方面介绍肾移植术后IgAN复发的最新进展,以期为临床肾移植术后IgAN复发的防治提供参考,改善肾移植受者的预后。     

重视延缓IgA肾病进展的基础和临床研究

免疫球蛋白A(IgA)肾病是以肾小球系膜区IgA沉积为特征的免疫复合物肾小球肾炎,是世界范围内最常见的原发性肾小球疾病,也是慢性肾脏病(CKD)的主要类型,约占我国原发性肾小球疾病的30%～40%。过去认为IgA肾病是预后良好的疾病,现在已明确IgA肾病是进展性疾病,诊断后每10年约有20%的患者进展到慢性肾功能衰竭,IgA肾病现在仍然是我国慢性维持性血液透析的首位原发病。因此,我们应该重视探索IgA肾病的病因和发病机制,尽最大可能延缓IgA肾病肾功能的恶化,减少尿毒症的发生。一、对IgA肾病发病及进展机制的认识到目前为止,关于原发性IgA…     

IgA肾病患者IgA1对足细胞nephrin mRNA表达的影响

近年研究发现IgA肾病患者的血清IgA1与正常人相比具有明显的异质性,其中起致病作用的主要是聚合型IgA1（polymeric IgA1,pIgA1）。新近研究也发现IgA肾病（IgAN）不仅是系膜细胞受累的疾病,而且在疾病的发生发展过程中也存在着足细胞的破坏。目前关于患者血清IgA1分子异常和足细胞损伤之间有何关系尚不清楚,我们亦未检索到相关报道。本研究拟观察IgAN患者血清IgA1对足细胞分子nephrin表达的影响。     

Increased expression of HLA-DR molecule on peripheral blood Th lymphocytes from patients with IgA nephropathy

Background. IgA nephropathy is the commonest type of glomerulonephritis. Recent studies have shown a decrease in the expression of HLA class I antigens on peripheral blood mononuclear leukocytes (PBML) from patients with HLA class II-associated autoimmune diseases. In this study, the expression of HLA molecules on T cells from patients with IgA nephropathy was examined in order to investigate the immunological events contributing to the pathogenesis of this disorder. Methods. Thirty Japanese patients with IgA nephropathy were studied. Nine patients with membranous nephropathy and 21 sex- and age-matched healthy individuals were enrolled as controls. Heparinized PBML with or without stimulation by an anti-CD3 monoclonal antibody were analyzed in regard to the expression of HLA-class I, HLA-DR, CD4, CD8, CD11a, CD11b, and CD56, by two-color fluorescence flow cytometry. Results. The expressions of HLA-class I, HLA-DR, CD11a, CD11b, and CD56 on resting CD3-positive, CD4-positive, CD8-positive, or CD20-positive cells from patients with IgA nephropathy were found to be comparable with those from the controls. However, after stimulation by anti-CD3 antibody, the expression of HLA-DR on CD4-positive cells from these patients was significantly higher than that from the controls. Further, the expression of HLA-DR on CD4-positive cells from patients with proteinuria of more than 1 g/day was much higher than that in patients with proteinuria of less than 1 g/day. Conclusions. In this study, the expression of HLA-DR on stimulated Th cells from IgA nephropathy patients was shown to be significantly higher than the expression in the stimulated T cells from the controls. This finding suggests that Th cells may acquire antigen-presenting activity by HLA-DR expression, present antigens to other Th cells, promote B cells to produce antibodies, and, presumably, lead to the development of IgA nephropathy. Received: October 26, 1998 / Accepted: February 16, 1999     

MicroRNAs in IgA nephropathy

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is considered that the pathogenesis of IgAN involves the ‘multiple hit theory’ and the immune-inflammatory mechanism; however, these theories have certain limitations. The gold standard for diagnosing IgAN is still renal biopsy. Although renal biopsy is accurate, it is traumatic and is associated with some risks and limitations, so there is a need for non-invasive diagnostic methods. According to recent studies, microRNAs (miRNAs) play important roles in the occurrence and development of IgAN; thus, they provide the possibility of the noninvasive diagnosis of IgAN and also have some value in predicting prognosis. This review summarizes the current research status of miRNAs in the occurrence, development, diagnosis, and prognosis of IgAN. We also highlight some interesting and challenging points that require further study.     

Specific binding of circulating IgA antibodies in patients with IgA nephropathy

Detection of circulating IgA antibodies which are specific in patients with IgA nephropathy is described. Freeze and thawed extracts of pharyngeal cells obtained from patients with IgA nephropathy, other glomerular diseases, and healthy adults were cultured with fibroblasts such as Vero or Hel cells at 37 degrees C for 2 weeks. Serum samples were obtained from these patients and healthy adults. The cultured fibroblasts were fixed on slide glasses, and then incubated with the serum samples from the same or other patients with IgA nephropathy. The cells were stained with FITC-labeled heavy-chain specific anti-human IgA antiserum and then examined with a fluorescent microscope. It was demonstrated that the IgA antibodies in sera obtained from patients with IgA nephropathy or HSP nephritis were bound with the nuclear regions of such fibroblasts. It was suggested that IgA antibodies in sera could be bound with some antigenic substances which were transferred from pharyngeal cells of patients with IgA nephropathy to fibroblasts in vitro.     

贫血加重IgA肾病患者的临床和病理改变

目的 分析IgA肾病合并贫血患者的临床病理特征.方法 收集经肾活检确诊的IgA肾病患者临床资料409例,按照贫血与否分为非贫血组和贫血组,回顾性分析两组患者的临床和病理资料.结果 与非贫血组比较,贫血组患者的肾小球损伤和肾小管间质萎缩程度较重、24 h尿蛋白增多和eGFR降低.Spearman相关分析结果显示,血红蛋白、eGFR与肾脏病理损伤呈负相关(P＜0.05),血尿酸、24h尿蛋白与肾脏病理损伤呈正相关(P＜0.05).多因素Logistic回归分析发现贫血是肾小管间质萎缩的独立危险因素.结论 IgA肾病合并贫血患者的临床和病理损伤重于IgA肾病非贫血的患者,贫血参与IgA肾病的进展.     

可溶性血管内皮生长因子受体1在IgA肾病中的临床意义

目的 探讨可溶性血管内皮生长因子受体1 （soluble fms-like tyrosine kinase-1,sFlt-1）在IgA肾病中表达变化的临床意义与病理类型之间的关系.方法 选取2005年1月至2013年3月期间内蒙古自治区医院经肾活检确诊为IgA肾病的80例患者作为病例组,选30名健康献血者作为对照组,测定两组所有人员血浆中sFlt-1表达水平.将80例病例组患者按IgA肾病病理表现分为新月体形成组（36例）及硬化肾小球组（20例）,另有24例IgA肾病患者同时存在新月体形成及硬化肾小球,对比sFlt-1在新月体形成组和硬化肾小球组的相关性.结果 病例组血浆sFlt-1明显高于对照组（P＜0.01）;病例组中新月体形成组的患者血浆中sFlt-1含量明显升高,硬化肾小球组患者血浆中sFlt-1含量相对偏低,sFlt-1与新月体比例呈正相关,而与硬化肾小球比例不相关.结论 检测sFlt-1在IgA肾病中有重要的临床意义,sFlt-1与IgA肾病病理类型有相关性.     

IgA肾病患者肾脏组织中差异细胞因子的探索研究

目的筛选IgA肾病(IgAN)患者肾脏组织中的差异蛋白质-细胞因子,进一步探讨IgAN的发病机制。 方法入选年龄18～60岁,解放军总医院肾脏病科住院肾活检确诊为IgAN患者10例;泌尿外科行肾癌肾脏切除的患者10例,取癌旁6 cm以外正常肾脏组织作为对照。肾脏组织利用L-493细胞因子抗体芯片进行检测,筛选差异蛋白质,并对差异蛋白质进行基因本体论(GO)分析。以IL-33(白介素-33)利用酶联免疫吸附试验(ELISA)进行验证。采用IBM SPSS Statistics 19.0软件对结果进行统计分析,利用T检验对差异蛋白质进行筛选,P<0.05,并且差异蛋白质差异倍数>1.4认为是差异蛋白质。 结果L-493细胞因子抗体芯片检测,在20例患者中(IgAN组10例,对照组10例),发现了25种差异蛋白质,GO分析结果表明：这些蛋白质主要与应激、细胞粘附、蛋白质代谢、信号转导相关。ELISA验证结果显示：IgAN患者肾组织中IL-33表达水平显著高于对照组。 结论IgAN患者肾脏组织中差异表达蛋白质直接或间接调控着炎症、细胞增殖和凋亡及纤维化过程。IL-33可能与IgAN发病机制有关。     

家族性IgA肾病--777例中国IgA肾病回顾性调查分析

目的报道中国家族性IgA肾病(FIgAN)发生情况以及临床病理特征,提高对家族性IgA肾病的认识。方法利用肾脏疾病数据库IgA肾病子库中我院1988～2001年收集的777例IgA肾病患者,进行家族史调查,以及部分家庭成员中行尿常规肾功能检查确定FIgAN发病情况,比较家族性与家族史阴性的IgA肾病患者临床表型的差异。结果(1)在调查的777例IgA肾病患者中,35例患者同时合并薄基底膜肾病,另外742例患者中,65例IgA肾病患者家族史阳性,占8.7%,其中10例(1.3%)患者为FIgAN,55例(7.4%)为可疑家族性IgA肾病。(2)与家族史阴性的患者相比,FIgAN患者在发病年龄、性别、肾穿时的血压、血尿、蛋白尿、肾功能上差异无显著性意义。结论FIgAN在中国人并非少见,加强家系调查特别是在IgA肾病患者亲属中常规进行尿检查将有助于发现该病。家族性IgA肾病诊断应强调同时电镜检查以除外薄基底膜肾病和早期Alport综合征。初步研究提示,本组患者与家族史阴性的IgAN患者相比,其临床病理表现不具有特征性。     

IgA肾病患者IgA1糖基化异常及其致病机制

IgA肾病(IgAN)是导致终末期肾病最常见的原发性肾小球疾病。其病理特点为IgA1在肾小球系膜区沉积,IgA1分子的异常糖基化是导致IgAN发病的关键因素。多种与IgAN相关的基因位点已经被发现。这些基因编码的细胞因子参与了IgA1糖基化异常的发病机制。此外糖基化酶缺乏、分子伴侣甲基化异常都可能导致IgA1异常糖基化。异常糖基化的IgA1可通过自我聚集或形成免疫复合物沉积于系膜区,进而刺激系膜细胞增殖、分泌系膜基质、细胞因子、趋化因子、生长因子等,导致肾小球损伤。对IgA1异常糖基化的深入研究有助于了解IgA肾病的发病机制并提供新的诊断与治疗措施。