IgA肾病患者临床与病理分析

目的探讨IgA肾病患者的临床表现和肾脏病理的特点及其相互关系。方法收集62例IgA肾病患者的临床资料及肾脏病理资料并进行统计学分析。结果病理类型中以系膜增生性、局灶节段增生性、局灶节段性硬化症三种最多，共占90．32％。Lee氏病理分级中以Ⅲ、Ⅳ级最多，共82．26％，随着Lee氏病理分级程度的增高。血压、血肌酐、血尿酸、24h尿蛋白量有不同程度的升高趋势（P〈0．05或P〈0．01）。Katafuchi积分与收缩压、血肌酐、血尿素氮、血尿酸、24h尿蛋白量呈显著正相关（P〈0．01）。结论IgA肾病肾脏病变与血压、肾功能、24h尿蛋白量等临床表现之间存在明显的相关关系。     

IgA肾病肾小球毛细血管内血浆蛋白淤积的临床病理意义

观察ＩａＡ肾病肾小球毛细血管内血浆蛋白平均吸光度变化与微血栓形成率、ＩｇＡ沉积量、临床表现及病理类型之间的关系。方法用图像分析仪定量测定５５例ＩｇＡＮ肾穿标本ＭＡＰＧ和ＩｇＡ沉积物,比较高ＭＡＰＧ组与低ＭＡＰＧ组之间微血栓形成率、ＩｇＡ沉积量、临床表现及病理类型的差异。     

Rapid Immunofluorescence Staining by Microwave Incubation in Patients with IgA Nephropathy

Abstract

The effect of microwave incubation on the immunofluorescence staining findings in renal tissues in patients with IgA nephropathy is described. Ten patients with IgA nephropathy were examined. The renal sections were incubated with FITC-labeled rabbit anti-human IgA, IgM, IgG, or C3 antisera in a microwave oven that was operated at 2,450 MHz with an output of 500 W. There was no significant difference in the distribution of IgA or C3 deposition in the glomeruli between incubation in the microwave for 3–7 sec and 4°C overnight incubation. However, the immunofluorescence intensity of IgA after microwave incubation was less than that after incubation at 37°C for 1 min to 2 hr or 4°C overnight incubation. The intensity or distribution of IgG and IgM deposition in the glomeruli was markedly less after microwave incubation than that after incubation of 4°C overnight. We conclude that rapid immunofluorescence by microwave incubation is useful in the examination of renal biopsy specimens, especially IgA and C3 staining findings in patients with IgA nephropathy. (The J Histotechnol 13:175, 1990)     

纤维连接蛋白及其受体在IgA肾病患者肾组织中的表达

为探讨纤维连接蛋白（ＦＮ）及其受体（ＦＮＲ）与ＩｇＡ肾病的关系，利用免疫组织化学和计算机图像分析的方法对４１例ＩｇＡ肾病患者和６例正常人肾组织中的纤维连接蛋白及其受体进行定量研究。结果表明，正常肾组织肾小球ＦＮ分布于系膜区，ＦＮＲ在肾小球系膜区毛细血管袢均有分布Ｉdisplay status     

IgA肾病中IgA1异常糖基化的致病机制

IgA肾病是最常见的原发性肾小球疾病,是发展为终末期肾病的主要病因,其病理机制复杂,临床表现多样化,组织形态学改变轻重不一。IgA肾病以肾小球系膜区IgA1沉积为病理特征,肾脏沉积的IgA1分子铰链区O-糖链半乳糖基减少,致使IgA1分子易于自身聚集并沉积在肾小球。糖基化酶缺乏、基因突变、免疫紊乱都可能导致IgA1异常糖基化的发生。IgA1分子的异常糖基化是IgA肾病发病的关键因素,但其具体产生原因和致病机制仍未明确,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治疗方向。     

Computer Imaging Analysis of Glomerular Extracellular Components in Patients with IgA Nephropathy

Computer imaging analysis was used for quantitative evaluation of the extents, amounts and distributions of glomerular extracellular components, such as the 7S and NC 1 domains of type IV collagen, laminin (LN), fibronectin (FN) and IgA, in glomeruli from patients with IgA nephropathy. Renal biopsy specimens from 13 patients with IgA nephropathy were incubated with mouse monoclonal antibodies against the FN or non collagenous (NC 1) domain of type IV collagen or polyclonal antiserum against the LN or 7S domain of human type IV collagen, and then stained with appropriate dilutions of FITC labeled anti mouse Ig antisera. Marked staining of the 7S or NC 1 domain of type IV collagen, LN or FN was detected in the glomerular capillary walls and/or mesangial areas in patients with IgA nephropathy. In particular, a prominent increase of FN was observed in the subendothelial regions of glomerular capillary walls, i.e. mesangial interposition, in the moderate or advanced stage of IgA nephropathy. Therefore, computer imaging analysis was shown to be useful for the quantitative determination of such components distributed in glomeruli from patients with IgA nephropathy. Acta Pathol Jpn 39: 296 305, 1989.     

IgA肾病中肾小动脉增厚及其临床评价

目的:目的观测IgA肾病肾小动脉病理学改变,探讨小动脉增厚与临床症状及病理学改变的关系.方法:选内蒙古地区汉族110例IgA肾病患者,医学图像分析系统单盲法测算小动脉血管腔内径与血管外径比值,分析小动脉增厚与临床症状及病理学改变的关系.结果:①IgA肾病小动脉增厚可表现为肌层增厚或玻璃样变性,造成管腔狭窄,两者可共存....     

The juxtaglomerular apparatus in IgA nephropathy: An analysis of the transport and fate of IgA deposits at the glomerular hilus

Summary This study on 27 cases of IgA nephropathy has shown that IgA deposits are rare in the juxtaglomerular apparatus (JGA) despite large amounts of IgA deposits in the mesangium. Phagocytes are absent in JGA. A small number of ill-defined, IgA-positive substances are seen in the matrix of lacis cells, and their electron-density is decreased. These findings indicate dissolution of IgA deposits in the intercellular matrix. In addition, it is suggested that the transport of IgA deposits through the glomerular stalk toward JGA is prevented at the border area between the mesangium of glomerular hilus and the lacis cell region. The block is not complete, because small, IgA-positive substances are seen sparsely in the matrix of lacis cells. The structure of the lacis cell region is thought to restrict the passage of macromolecules such as IgA deposits. Frequently positive staining for C3 in the mesangium and lacis cell region and within the wall of afferent and efferent arterioles indicates that C3 is easily accessible to the arteriolar wall adjacent to JGA, by the route through the glomerular stalk and JGA. This may be concerned in the pathogenesis of arteriolar hyalinosis at the glomerular hilus.     

IgA肾病基因多态性研究进展

IgA肾病是肾小球系膜病变的一个特殊类型,基因多态性可能与IgA肾病的产生和发展有关,不同基因型的病人其临床表现或病理类型也可能存在差异,而该病可能与多种基因有关,研究较多的有:肾素血管紧张素系统基因多态性、子宫球蛋白基因多态性、MBP多态性、细胞因子多态性、TGF-β1的基因多态性等。目前国内外学者的研究结果还不完全一致,这是由于基因多态性与种族、性别有关,本文仅对已有研究作一综述。     

IgA Nephropathy: An Ultrastructural Study

From a series of 333 renal biopsies examined by immunofluorescence microscopy, 231 specimens corresponded to primary glomerulonephritis unassociated with systemic diseases. Of those 231 biopsies, 39 had diffuse mesangial deposits of IgA (16.8%). Thirty cases of IgA nephropathy had one to several glomeruli in the Epon-embedded tissue. All cases showed mild to moderate increase of mesangial cells and matrix. Mesangial deposits were present in all cases; subendothelial (5/30), intramembranous (3/30), and subepithelial (10/30) deposits were also found. Occasional dense granular deposits involved the basement membrane of the capsule of Bowman (1/30) and the subendothelial region of some extraglomerular arterioles (2/30). Thinning (6/30) and splitting (4/30) of the glomerular lamina densa appeared focally in some cases.     

不同性别IgA肾病患者相关临床指标及病理特点对比

目的 通过对不同性别IgA肾病患者临床指标及病理特点的对比,了解性别间相关指标的差异,为临床积极有效的治疗该病提供依据。方法 回顾性分析2017年1月1日~2018年8月30日我院经肾穿刺活检确诊的361例IgA肾病患者的临床资料,比较不同性别IgA肾病患者的临床资料、危险度分级、病理分级及免疫荧光分型。结果 不同性别IgA肾病患者年龄、病程、舒张压、水肿、血尿、蛋白尿、血尿+蛋白尿、白蛋白、IgA、IgG、IgM、IgE、C3、C4、IgA/C3、肾小球滤过率、血钾、血钙、血磷、APTT、PT、FIB、左肾及右肾大小比较,差异无统计学意义（P＞0.05）;男性收缩压、血压高、肾功异常占比、胱抑素、肌酐、尿素、尿酸、甘油三脂、胆固醇、血钠、尿蛋白定量高于女性,差异有统计学意义（P＜0.05）。不同性别IgA肾病患者在1~3级占比比较,差异无统计学意义（P＞0.05）;男性IgA肾病患者在4级占比多于女性,差异有统计学意义（P＜0.05）。不同性别IgA肾病患者病理分级比较,差异无统计学意义（P＞0.05）。不同性别IgA肾病患者在IgA+IgM+C3、IgA+IgM+IgG、IgA+IgM+IlgG+C3占比比较,差异无统计学意义（P＞0.05）;男性IgA肾病患者在IgA+IgG+C3、IgA+C3分型中占比多于女性,差异有统计学意义（P＜0.05）。结论 男性IgA肾病的发病人数多于女性,且在IgA肾病中,男性的肾功能较女性差,推测其预后可能较差,因此当男性确诊为IgA肾病后,应更加关注其临床指标及病理相关指标,及早干预、及早治疗,制定合理地个性化治疗方案,延缓其进展。     

尿NGAL在IgA肾病肾小管间质损伤评估中的意义探讨

目的 探讨尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在IgA肾病(IgAN)患者肾小管间质损伤(TIL)评估中的意义.方法 应用酶联免疫法(ELISA)检测110例IgAN患者,30例非IgAN肾小球疾病患者以及30例健康对照者的尿NGAL水平.结果 IgAN组、非IgAN疾病对照组较健康对照组尿NGAL水平均明显升高(P＜0.01);IgAN组尿NGAL水平与多项临床病理指标明显相关;影响尿NGAL水平的独立影响因素有血白蛋白水平,尿蛋白定量、尿NAG酶、尿渗透压,以及球性硬化、间质炎细胞浸润、间质纤维化、肾小管萎缩;以尿NGAL水平超过正常对照组2个标准差视为显著增高,联合NAG酶对有无TIL进行评估,ROC曲线下面积为0.850,明显优于血肌酐的0.675,灵敏度83.3％,特异度73.3％,准确率81.2％.结论 IgAN患者尿NGAL水平可以反映IgAN病情程度,在联合尿NGAL与尿NAG酶判别有无TIL时明显优于血肌酐及单纯的尿NGAL、尿NAG酶、尿渗透压等指标.     

IgA肾病肾阴虚证cDNA文库的构建

目的应用抑制性消减杂交（suppression subtractive hybridization,SSH）技术构建汉族人IgA肾病肾阴虚证cDNA消减文库。方法选择IgA肾病且中医辨证为肾阴虚证的患者以及正常人作为其对照组,进行正向和反向消减杂交。采用Trizol BD法提取总RNA,用SMART技术逆转录并扩增总cDNA,用RsaⅠ酶切基因组cDNA成大小不等的片段,分别与两种不同的接头连接,进行2次消减杂交及2次抑制性PCR,然后将PCR产物与U载体连接,经蓝白斑筛选后,再用PCR方法插入片段筛选出阳性重组质粒,构建IgA肾病肾阴虚证消减文库。结果用SSH方法筛选出了IgA肾病肾阴虚证的差异cDNA片段,其中正向消减文库共获得325个阳性克隆．反向消减文库获得306个阳性克隆,从而成功地构建了IgA肾病肾阴虚证的cDNA消减文库。结论SSH技术能够快速有效地分离差异cDNA片段,成功构建了IgA肾病肾阴虚证的cDNA文库,为进一步克隆肾阴虚证的相关基因奠定了基础。     

IgA肾病患者IL—2的产生及IL—2受体的表达

本文对IgA肾病(IgAN)外周血淋巴细胞白细胞介素2(IL-2)的产生、受体的表达及免疫球蛋白的产生进行了研究。结果发现:外周血淋巴细胞产生IL-2的活性明显增高,IL-2受体表达亦明显增强并伴有免疫球蛋白产生增多,提示IgAN存在着细胞免疫功能的紊乱。     

纳豆多糖改善小鼠IgA肾病的作用及其免疫学机制的研究分析

目的 探讨纳豆多糖改善小鼠IgA肾病的作用及其免疫学机制.方法 将造模成功的50只IgA肾病小鼠分为模型组,纳豆多糖高、中、低剂量组及阳性组(雷公藤多苷),每组10只.同时选择10只正常小鼠(未经造模)作为对照组.正常组和模型组小鼠按0.2 mL/10g 灌胃生理盐水(NS),阳性组(雷公藤多苷,5mg/kg),纳豆多糖高、中、低剂量组(给药剂量分别为40 、20、10 g/kg),1次/d,至第20周处死,取血及脏器,测定白蛋白、尿素氮、肌酐、血清循环免疫复合物和IgA水平.结果 与正常组比较,模型组尿微量白蛋白明显升高(P<0.05);与模型组比较,纳豆多糖高、中剂量组和阳性组尿微量白蛋白明显降低(P<0.05);与正常组比较,模型组尿血清白蛋白明显降低(P<0.05),与模型组比较,纳豆多糖高、中剂量组和阳性组血清白蛋白明显升高(P<0.05);与正常组比较,模型组尿素氮、肌酐、血清循环免疫复合物明显升高(P<0.05),与模型组比较,纳豆多糖高、中剂量组和阳性组尿素氮、肌酐、血清循环免疫复合物明显降低(P<0.05);与正常组比较,模型组肾组织IgA水平明显升高(P<0.05),与模型组比较,纳豆多糖高、中剂量组和阳性组IgA水平明显降低(P<0.05).结论 纳豆多糖可明显改善小鼠IgA肾病,还可降低尿蛋白和IgA水平.     

Induction of IgA against Haemophilus parainfluenzae Antigens in Tonsillar Mononuclear Cells from Patients with IgA Nephropathy

Much evidence suggests that IgA production in vivo and in vitro is enhanced in patients with IgA nephropathy (IgAN). We have demonstrated glomerular deposition of the outer membranes of Haemophilus parainfluenzae (HP) antigens (OMHP) and the presence of HP-specific IgA in the serum of patients with IgAN. In this study, we investigated the production of IgA and several cytokines by tonsillar mononuclear cells (TMC) from IgAN patients induced by stimulation with OMHP. The spontaneous production of total IgA and TGF-β by TMC from IgAN patients was higher than that by TMC from patients with chronic tonsillitis (CT) (P < 0.05). Stimulation with OMHP in vitro enhanced the production of HP-specific IgA by TMC from IgAN patients (P < 0.01), but not by TMC from CT patients. OMHP stimulation also enhanced the production of TGF-β and IL-10 by TMC from IgAN patients (P < 0.001). These results suggest that the infection of HP in the tonsil may be involved in the etiology of IgAN.     

68例维吾尔族IgA肾病患者MBL基因多态性与临床病理相关性分析

目的 探讨甘露糖结合凝集素(mannose-binding lectin,MBL)基因第54位密码子多态性与维吾尔族IgA肾病患者临床和病理的关系.方法 应用PCR-RFLP方法对68例维吾尔族IgAN患者进行MBL多态性检测,并与患者临床和病理特点进行相关性分析.结果 ①维吾尔族IgAN中表现为蛋白尿的患者突变型等位基因GAC的发生频率显著高于表现为单纯血尿的患者(P＜0.05);②维吾尔族IgAN中表现为复合性免疫沉积的患者等位基因GAC的发生频率显著高于表现为单纯免疫沉积的患者(P＜0.05).结论 MBL突变型等位基因GAC与维吾尔族IgAN 蛋白尿发生和免疫复合沉积相关.     

Progress in Molecular and Genetic Studies of IgA Nephropathy

Several new findings emerged recently from biochemical, genetic, and molecular studies of patients with IgA nephropathy. It appears that immunoglobulin A1-secreting cells of IgA nephropathy patients produce increased amounts of aberrantly glycosylated IgA1 in which the O-linked glycans in the hinge region are deficient in the content of galactose. The galactose-deficient IgA1 in the circulation is recognized by naturally occurring antibodies with anti-glycan specificity, and immune complexes are formed. These circulating immune complexes escape hepatic degradation and eventually are deposited in the kidney mesangium. Resident mesangial cells bind the IgA-containing immune complexes with the involvement of a novel IgA receptor and become activated. A familial form of IgA nephropathy has been linked to chromosome 6q22-23. Recent progress in molecular analyses of IgA nephropathy thus defines this disease as an autoimmune process with a novel IgA mesangial receptor and certain genetically determined traits.     

表现为孤立性血尿的IgA肾病36例临床分析

目的探讨表现为孤立性血尿的IgA肾病的临床特点及相关因素的影响。方法分析36例经肾活检确诊为孤立性血尿的IgA肾病患者的临床表现特点、病理特征及相关因素。结果孤立性血尿的IgA肾病患者以镜下血尿为主要临床表现,伴有腰痛、咽干咽痛、疲劳者较多。病理特征以系膜增生性肾小球肾炎为主,Lee病理分级分布以Ⅱ～Ⅲ级为主。结论孤立性血尿的IgA肾病患病率较高,全身症状较轻,易被忽视,容易造成漏诊,应引起临床诊治的足够重视。     

GSTT1基因多态性与IgA肾病易感性的研究

目的：了解谷胱甘肽硫转移酶T1（glutathion S-transferase-theta）基因多态性与内蒙古包头地区汉族人群IgA肾病易感性的相关性。方法：利用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测。随机收集包头医学院第一附属医院肾内科IgA肾病患者110例为病例组,健康体检正常者113例作为对照组。结果：GSTT1基因缺失型频率在IgA肾病患者组中为49.1%（54/110）;在正常人体检组中为53.1%（60/113）,（χ2=1.527,P〉0.05）。二者之间差异无统计学意义。结论：GSTT1基因多态性与内蒙古包头地区汉族人群IgA肾病发生无相关性。