补体膜攻击复合物和CD59在不同免疫病理类型IgA肾病发病机理中的作用

为进一步阐明导致不同免疫病理类型ＩｇＡ肾病（ＩｇＡＮ）患者预后不同的机理，应用ＰＡＰ四层法对２８例肾小球单纯ＩｇＡ沉积（单纯ＩｇＡ组）及３２例ＩｇＧ、ＩｇＡ、ＩｇＭ共同沉积（ＧＡＭ组）ＩｇＡＮ患者肾组织膜攻击复合物（ＭＡＣ）和ＣＤ５９的分布情况，结合其肾小球内沉积的补体成分以及病理改变和临床特点进行了分析，结果表明：单纯ＩｇＡ组临床表现、病理改变轻，ＧＡＭ组临床表现、病理改变重。ＧＡＭ组肾组织经典途径补体成分Ｃｌｑ、Ｃ４沉积（均为Ｐ＜０．０１），肾小球系膜区及毛细血管袢ＭＡＣ沉积（分别为Ｐ＜０．０５、Ｐ＜０．０１），肾小球硬化＞２５％（Ｐ＜０．０５）和中重度小管间质病变的发生率（Ｐ＜０．０５），均较单纯ＩｇＡ组明显增多，且ＧＡＭ组皮质区域间质面积较单纯ＩｇＡ组明显增宽（Ｐ＜０．０１）。尽管ＣＤ５９在两组中分布无统计学差异，但若按肾小球ＣＤ５９分布强度将患者分为Ａ组（＋）和Ｂ组（２＋），结果发现ＣＤ５９Ａ组肾小球硬化＞２５％（Ｐ＜０．０５），中重度小管间质病变的发生率明显增多（Ｐ＜０．０１），皮质区域间质面积明显增宽（Ｐ＜０．０１）。在硬化的肾小球内ＭＡＣ分布多而ＣＤ５９分布少     

成人原发性肾小球肾炎远期预后的观察：（附1071例？…

目的：前瞻性观察各种病理类型原发性肾小球肾炎患者的远期预后,了解影响肾小球肾炎预后的各种因素。方法：１９８０年１月～１９９６年月１２月间,在本院经肾活检确诊并常年定期随访的原发性肾炎患者共１０７１例,其中ＩｇＡ肾病（ＩｇＡＮ）４７１例（４４．３％）、系膜增生性肾炎（ＭｓＰＧＮ）２６８例（２５．０％）、ＩｇＡ肾病（ＩｇＭＮ）８０例（７．３０％）、膜增生性肾小球肾炎（ＭＰＧＮ）６８例（６．３０％）、膜     

大黄治疗大鼠系膜增殖性肾炎的实验研究

为了解中药大黄对系膜增殖性肾炎的治疗效果，用计算机图像分析及ＥＬＩＳＡ法观察了大黄对抗Ｔｈｙ－１肾炎大鼠系膜区细胞外基质的影响，并检测了肾小球培养上清中的白细胞介素－１（ＩＬ－１）活性。结果表明，大黄不仅减少了肾炎大鼠基质的堆积，还能降低肾小球培养上清中的纤维连接蛋白（ＦＮ）浓度和ＩＬ－１活性。肾小球ＦＮ浓度在未治疗组非常显著地高于对照组与大黄组（Ｐ＜０．０１），其中大黄组又显著低于对照组（Ｐ＜０．０５）。肾小球ＩＬ－１活性未治疗组显著高于大黄组，而大黄组又显著高于正常对照组（Ｐ＜０．０５）。大黄能改善系膜增殖性肾炎大鼠系膜区基质的堆积，其作用可能与其抑制肾小球分泌ＩＬ－１有关。     

肾脏疾病时载脂蛋白在肾小球沉积的临床意义

目的了解载脂蛋白（Ａｐｏ）Ｂ及Ｅ在肾脏的沉积和肾脏疾病的关系。方法对４３例肾脏疾病患者的肾脏活检标本进行免疫组化分析，同时进行系列的临床观察。结果ＡｐｏＢ和ＡｐｏＥ在肾脏疾病时多数呈颗粒状沉积在肾小球系膜和毛细血管襻内，ＡｐｏＢ和ＡｐｏＥ沉积均阳性者有明显的弥漫系膜细胞及基质增生，同时有明显的肾小球粘连和硬化。此外尚发现ＡｐｏＢ阳性组和ＡｐｏＢ及ＡｐｏＥ均阳性组蛋白尿，肾功能损害更严重（Ｐ＜００５）。结论ＡｐｏＢ和ＡｐｏＥ在肾脏的沉积可引起明显的肾小球系膜损害，加速肾小球硬化，并引起比较严重的蛋白尿和肾功能减退。     

血清IgA—纤维连接蛋白聚合物在IgA肾病诊断中的意义

为探讨血清ＩｇＡ－纤维连接蛋白（ＦＮ）聚合物在ＩｇＡ肾病中的辅助诊断价值，对９１例ＩｇＡ肾病、１４例过敏性紫癜性肾炎、１１７例非ＩｇＡ肾脏病、２４例非肾脏病及２３４例健康人采用ＥＬＩＳＡ方法检测了血清中ＩｇＡ－ＦＮ聚合物水平。结果显示，ＩｇＡ肾病血清该聚合物水平及阳性率（６１．５％）显著高于狼疮性肾炎（３０．８％）、其他非ＩｇＡ肾脏病（８．８％）、非肾脏病（０．０％）及健康人群（５．１％）（Ｐ＜０．０５），但与过敏性紫癜性肾炎组（４２．９％）差异无显著性（Ｐ＞０．０５）。提示该聚合物对ＩｇＡ肾病具有一定的辅助诊断价值。但因在过敏性紫癜性肾炎及狼疮性肾炎时也有较高的阳性率，应注意鉴别。     

间质性肺疾病支气管肺泡灌洗液中FN和IgG的临床研究

同步检测并对比１１例正常对照者和２５例间质性肺疾病（ＩＬＤ）病人支气管肺泡灌洗液（ＢＡＬＦ）和外周血中纤维连接素（ＦＮ）和ＩｇＧ水平并探讨其意义。结果表明：（１）正常人ＢＡＬＦ和外周血中ＦＮ水平相近（Ｐ＞０．０５）；ＩＬＤ病人ＢＡＬＦ中ＦＮ水平明显增加，并高于其血浆中ＦＮ水平（Ｐ＜０．０１），而各组血浆ＦＮ水平相近（Ｐ＞０．０５）。（２）ＩＬＤ病人ＢＡＬＦ中ＩｇＧ水平明显增加，外周血中ＩｇＧ水平也略有增加。（３）ＩＬＤ病人ＢＡＬＦ中ＦＮ、ＩｇＧ均与细胞总数呈正相关，其中ＩＰＦ组ＢＡＬＦ中ＦＮ与中性粒细胞（％）呈正相关（Ｐ＜０．０５），非ＩＰＦ组ＢＡＬＦ中ＦＮ、ＩｇＧ均与淋巴细胞（％）呈正相关（ＦＮ：Ｐ＜０．０１；ＩｇＧ：Ｐ＜０．０５）。（４）ＩＬＤ病人ＢＡＬＦ中ＦＮ和ＩｇＧ之间呈明显的正相关（Ｐ＜０．０１）。以上结果提示：ＩＬＤ病人ＢＡＬＦ中ＦＮ水平明显增加，它可作为ＩＬＤ肺泡炎活动性的一个标志，而ＢＡＬＦ中ＩｇＧ水平增高可能反映ＩＬＤ体液免疫活动性的一个侧面。     

肾病综合征及其高凝状态的治疗

本文报告肾病综合征及其高凝状态的治疗结果。在病程中，膜性肾小球肾炎、膜增殖性肾小球肾炎和微小病变易出现肾病综合征。发生率分别为２９．８％，２８．８％，１９．２％。治疗前病人的白陶土部分凝血活酶（ＫＰＴＴ）试验缩短（Ｐ＜０．０５），肾上腺素诱导的血小板凝集力显著增高（Ｐ＜０．０１），ＡＴⅢ显著降低（Ｐ＜０．０１）及血纤维蛋白原显著增高（Ｐ＜０．０１），促使血液凝固，血管内形成血栓。给严重的肾病综合征而无高血压的病人多次输注血浆后，达到了平均动脉压（Ｐ＜０．０１）。应用肝素和／或尿激酶治疗后改善了高凝参数和肾功能，显著减少了尿蛋白。     

61例婴幼儿肾小球疾病的临床与病理

对６１例婴幼儿肾小球疾病患儿进行肾穿刺检查，其中急性肾炎４例，迁延性肾炎１例，无症状性蛋白尿或血尿３例，单纯性肾病４５例，肾炎性肾病７例，先天性肾病综合征１例。病理类型：毛细血管增生性肾炎７例，微小病变５例，系膜增生性肾炎２６例，ＩｇＡ肾病５例，ＩｇＭ肾肩１０例，膜性肾病７例，局灶节段性肾小球硬化１例。完全经解４９例（８８．５％），部分缓解６例（９．８％），无效１例（１．６％）．结果表明，婴幼儿肾小球疾病的病理类型以系膜增生性肾炎为主，微小病变只占８．２％。婴幼儿肾小球疾病的疗效较好。     

纤维样变肾小球病：——附四例报告

报告４例纤维样变肾小球病。４例病人无系统性疾病，主要临床表现为高血压，大量蛋白尿、镜下血尿。２例有不同程度的肾功能减退。光镜下病理类型为膜增殖性肾炎（２例）、膜性肾病（１例）和系膜增生性肾炎（１例），病理改变均较重，刚果红染色阴性；免疫荧光多数病例（３１４例）以ＩｇＧ、Ｃ＿３为主，呈颗粒样在肾小球系膜区和（或）沿肾小球毛细血管壁沉积；电镜下可见大量纤维样物质在肾小球系膜区和（或）肾小球基底膜内分布，纤维样物质直径经图象分析仪测量为２０．５０±１０．３７ｎｍ。本病诊断主要依靠超微结构检查。本病为国内首次报道。     

大黄对糖尿病大鼠肾小球形态改变的影响及定量分析

用先进的图像分析系统，观察了中药大黄提取物Ⅰ号对链脲菌素（ＳＴＺ）所致糖尿病肾病大鼠模型肾小球形态学的影响，结果提示，在病程第三天糖尿病组大鼠肾小球干均体积较大黄提取物Ⅰ号治疗组大鼠明显增大（Ｐ＜０．０１）；病程的第三、七和第１４天糖尿病组大鼠肾小球系膜区平均面积较治疗组扩大，有统计学差异（分别为Ｐ＜０．０１．Ｐ＜０．０１和Ｐ＜０．００１）．本研究在实验性大鼠的体内进一步证实大黄提取物Ⅰ号抑制肾脏肥大的作用。     

甘露糖结合蛋白基因多态性与IgA肾病免疫病理类型的关联

目的根据甘露糖结合蛋白(MBP)基因多态性对其功能的影响,探讨MBP基因多态性与IgA肾病免疫病理间的联系。方法选取1钾例IgA肾病(IgAN)患者,其中77例为肾小球单纯IgA伴沉积,70例为肾小球IgA,IgG,IgM伴C3,C1q沉积。使用PCR-RFLP方法对MBP基因多态性与IgAN免疫沉积的关系进行了观察。结果①本研究中正常人群MBP基因多态性分布与文献报道的华人及高加索人种接近并无显著差异。②IgAN中大量免疫沉积(IgA,IgG,IgM,C3,C1q)患者MBP基因CGC／GAC基因型的发生频率明显高于单纯IgA沉积(IgA,C3)患者(41.4％vs19.5％,P＜0.01),而CGC／GGC基因型的发生频率明显低于单纯IgA沉积患者(55.7％vs76.6％,P＜0.01)。IgAN的大量免疫沉积患者GAC等位基因的发生频率明显高于单纯IgA沉积患者(0.236vs0.136,P＜0.05),而GGC等位基因的发生频率明显低于单纯IgA沉积患者(0.764vs0.864,P＜0.05),GAC等位基因与IgAN的大量免疫沉积明显相关(OR=1.95,95％CI1.06～3.58)     

Relationship between serum IgA/C3 ratio and progression of IgA nephropathy

OBJECTIVE: The serum IgA/C3 ratio might be considered to serve as a diagnostic marker for patients with IgA nephropathy (IgAN), but its value as a marker of the severity of histological lesions or prognosis is unknown. METHODS: We studied the serum IgA/C3 ratio, using standardized reference material, in 86 patients with IgAN and in 32 with non-IgAN. The patients with IgAN were divided according to the severity of histological lesions (mild IgAN, n=29 and severe IgAN, n=57) based on Japanese clinical guidelines. RESULTS: The serum IgA level was significantly higher, while its C3 level was lower in patients with severe IgAN compared to those with non-IgAN. However, these levels were not different between patients with mild IgAN and non-IgAN. In contrast, the serum IgA/C3 ratio obviously differed among the three groups (2.47+/-0.96 vs. 3.63+/-1.44 vs. 4.72+/-1.86; p<0.01, ANOVA). Kaplan-Meier analysis of the patients with IgAN classified according to the mean serum IgA/C3 ratio revealed that the group with high serum IgA/C3 (4.5 and above) had a significantly poorer renal outcome (p<0.05, log-rank test), since the cumulative renal survival rate at 5 years was 84.4% vs. 100%. The ratio (%) of patients with severe IgAN in whom hematuria disappeared, was significantly higher in the low, than in the high serum IgA/C3 group (41.9% vs. 15.4%; p<0.05, t-test). CONCLUSION: The serum IgA/C3 ratio appears to reflect the histological severity of IgAN and could serve as a marker of the progression of IgAN.     

Monoclonal antibody against laminin a and b chains: preparation and its clinical application

In present study, we developed a hybridoma cell line which secretes monoclonal antibody against Laminin (Mo-611). The MoAb produced was identified to be isotype of IgG1. It reacted with Laminin obtained from murine EHS sarcoma, the intensity of reaction declined in accompany with increment of dilution, and could be absorbed by Laminin in 1 u/ml. On western blotting, it bounded to Laminin A chain 400 KD and Laminin B chain 200 KD. On IF study of renal tissue, positive staining with Mo-611 could be detected in fetal GBM and TBM, normal adult glomerular mesangial area and cytoplasm of tubular epithelium. In case of IgA nephropathy, the amount of deposits in mesangial area increased while in membranous nephropathy deposits along the capillary loop was also abundant in amount. In conclusion, the clinical application of McAb against Laminin might be helpful in the immunopathological diagnosis of glomerular diseases.     

肾小球肾炎肾组织megsin的表达及其意义

目的 :观察megsin在肾小球肾炎患者肾小球内表达及其特点 ,对原发性肾小球肾炎 (IgA肾病 ,IgAN)和继发性肾小球肾炎 (狼疮性肾炎 ,LN)进行研究。　 方法 :应用针对人类megsin的多克隆抗体 ,采用免疫组化法检测肾活检组织中肾小球内megsin的表达 ,其中IgAN 10例、LN 2 0例 ,并采用半定量方法与正常肾组织和轻微病变性肾病进行比较。　 结果 :正常肾组织和轻微病变性肾病均可表达一定量的megsin ,而在IgAN和LN的肾小球内megsin均表达明显增加。megsin仅表达于肾小球系膜区域 ,小管间质未见表达。在IgAN系膜增生性病变中megsin表达量较硬化性病变明显增多 (P <0 0 5 )。而在LN肾小球megsin的表达量虽较正常肾组织和轻微病变型肾病显著增多 ,但与原发性肾小球肾炎IgAN相比较 ,其表达量少 ,即使在LNⅣ型时。　 结论 :megsin在原发性和继发性肾小球肾炎均有一定的表达 ,并在其疾病进程中以及肾小球系膜功能调节中起一定作用 ,但在原发性和继发性肾小球肾炎中megsin的表达调节可能存在不同的机制     

Immunoglobulin A nephropathy.

Of 475 renal biopsles examined by immunofluorescence, IgA was seen located selectively in the glomerular mesangium of 18 patients. These patients were generally young men and had hematuria, only minimal proteinuria, and normal renal function. Glomerular lesions consisted of focal segmental capillary hypercellularity or sclerosis and mesangial thickening due to an increase in mesangial cells, matrix, and electron-dense deposits. Both IgG and C3 were frequently seen with IgA in the mesangium as was properdin in five of six cases, but C4, a component of the classical pathway of complement activation, was seen only infrequently. Serum IgA levels were elevated in many patients, but serum complement components were normal. These findings suggest a possible unusual immune pathogenesis with local mesangial binding and alternate pathway activation of complement.     

41例抗肾小球基底膜抗体相关疾病的临床和病理分析

目的了解抗肾小球基底膜（GBM）抗体相关疾病的不同临床类型及其临床病理特点。方法对我科近6年来检测出的41例抗GBM抗体相关疾病的临床病理资料进行回顾性分析。结果22/41例为Goodpasture病（GP）,其中2例肾功能正常。32/41例患者为单纯抗GBM抗体阳性,其中31/32例男性,平均年龄（26.8±9.7）岁。9/41例抗GBM抗体伴抗中性粒细胞胞浆抗体（ANCA）阳性,其中7/9例为女性,平均年龄（44.5±19.6）岁。两组在性别和发病年龄上差异有显著性（P＜0.05）。32/41例作了肾活检,平均发病至肾活检时间为（62.7±43.5）d。2/32例肾功能正常的GP患者为轻度系膜增生性肾炎。30/32例为新月体肾炎,其中24/30例（80%）患者的肾小球100%受累,多伴有毛细血管襻和球囊严重破坏。免疫荧光检查仅16/23例呈典型的IgG、C3沿肾小球毛细血管襻（GCW）呈线样沉积;7/23例表现为IgG和（或）C3等沿GCW呈细颗粒状沉积,少数伴有系膜区沉积。典型和不典型的免疫荧光改变与光镜病理的严重程度不相关（P＞0.05）。所有患者均有贫血、血尿和蛋白尿,其中7/41例表现为肾病综合征。经强化免疫抑制治疗,4例患者临床完全缓解或好转,包括2例轻度系膜增生性肾炎的GP患者。其余患者均依赖肾脏替代疗法或死亡。结论中国人抗GBM抗体相关疾病并不少见。单纯抗GBM抗体组多发于青年男性,双抗体阳性组多发于中老年女性。抗GBM抗体相关疾病多预后差,肾脏病理多为新月体性肾炎,但免疫病理并非均表现为典型的IgG、C3沿GCW呈线条样沉积。仅少数无少尿的轻型患者或肾功能损伤轻者可临床完全缓解或好转。     

New insights in the pathogenesis of IgA nephropathy

IgA nephropathy (N) or Berger's disease is the most common form of primary glomerulonephritis worldwide and one of the first cause of end-stage renal failure. The disease is characterized by the accumulation in mesangial areas of complexes containing polymeric IgA1. The mechanisms involved in the pathogenesis of IgAN is only now emerging. We discussed here three essential points: (i) the generation of abnormal IgA1 and formation of IgA1 complexes; (ii) the generation of mesangial injury mediated by interaction of IgA1 complexes with mesangial IgA1 receptors, and (iii) the progression of IgA-mediated mesangial injury towards renal failure. In summary, our data reveal that quantitative and structural changes of IgA1 play a key role on the onset of the disease due to functional abnormalities of two IgA receptors: the Fc alphaRI (CD89) expressed by blood myeloid cells and the transferrin receptor (CD71) on mesangial cells. Abnormal IgA induces release of soluble CD89 soluble leading to the formation of circulating IgA complexes, which in turn may be trapped by CD71 that is overexpressed on mesangial cells in IgAN patients allowing formation of IgA1 deposits. The elucidation of IgA-receptor interactions may open new avenues for drug design and treatment of IgAN.     

Immunofluorescence staining of renal biopsy samples in patients with diabetic nephropathy in non-insulin-dependent diabetes mellitus using monoclonal antibody to reduced glycated lysine

This is the first report on immunofluorescence staining of renal biopsy samples in human diabetic nephropathy (DN) using monoclonal antibodies to reduced glycated lysine. In order to detect the localization of glycated lysine in the mesangial matrix and/or the glomerular basement membrane (GBM), we examined immunofluorescence staining using antibodies against reduced glycated lysine in the glomeruli of 16 patients with DN and ten age-matched patients with diffuse mesangial proliferative glomerulonephritis without IgA deposition (DPGN) as controls. In the early stage of DN, immunofluorescence microscopy revealed the presence of intense staining for reduced glycated lysine in the GBM as well as in part of the tubular basement membrane, but not in the mesangial area. In contrast, immunofluorescence microscopy revealed less staining for glycated lysine in the GBM in the advanced stage of DN, and no reaction with any part of the renal tissue in patients with DPGN. It was concluded that detection of reduced glycated lysine in GBM in the early stage of DN might be associated with the initial pathogenesis of this disease.     

IgA肾病患者补体经典途径在血液及尿液中的活化及与肾损伤的关系

目的 研究循环系统中经典途径补体活化及调节方式在IgA肾病（IgAN）中的致病作用及与肾损伤的关系.方法 IgA肾病组30例,10例狼疮性肾炎（LN）患者作阳性对照,30例健康体检者作对照组.采用ELISA试剂盒检测IgA肾病患者和对照组血及尿液中经典途径补体激活标志物C1q、经典途径调节因子（sCR）1,分析补体浓度与肾组织病理结果及临床生化指标的相关性.将IgA肾病组患者按照病理Lee氏结果进行分组,Lee氏Ⅰ～Ⅲ级定为轻度损伤组,Lee氏Ⅳ～Ⅴ级定为重度损伤组,比较两组间的补体浓度差异.分析血C1q与sCR1间相关性.结果 IgA肾病组患者血清C1q及sCR1水平均高于对照组（P＜0.05）,而IgA肾病组与LN组间比较差异无统计学意义（P ＞0.05）;LN组患者尿液C1q浓度明显高于另外2组（P＜0.01）.当血清肌酐＞ 133μmol/L时,血C1q与肌酐水平呈显著负相关（P＜0.05）.尿C1q与肌酐水平呈显著正相关（P＜0.05）.Lee氏Ⅳ～Ⅴ级组患者血液及尿液C1q均明显低于Lee氏Ⅰ～Ⅲ级组（P＜0.05）.血sCR1与血C1q间呈显著正相关（P＜0.05）.结论 IgA肾病患者循环系统中可能存在补体经典途径激活通路,尤其是在肾损伤严重组,且与疾病的严重程度相关.IgA肾病中可溶型CR1对C1q存在介导调节作用.     

Mycoplasma pneumoniae pneumonia associated with IgA nephropathy

An 18-yr-old male developed Mycoplasma pneumoniae pneumonia associated with IgA nephropathy. In the biopsied renal tissue, immunofluorescence showed striking deposits of IgA, C3 and C3 activator in the mesangium, and electron microscopic examination showed electron-dense deposits in the mesangial region. When the patient's serum was preincubated with rabbit antiserum to human IgA, the passive hemagglutination titer for M. pneumoniae was much decreased. We suggest that in some cases, IgA nephropathy may follow infection by an organism which stimulates in IgA antibody response, leading to the formation of IgA antigen antibody immune complex deposits in the glomerular mesangium.