肾小球基膜和抗肾小球基膜抗体疾病

肾小球基膜(GBM)是肾小球滤过蛋白的主要屏障,它不但可作为免疫复合物的沉积处,它的某些成份还可作为抗原引起相应的抗体,产生抗 GBM 抗体疾病。现认为 Goodpasture 综合征(肺肾综合征)与抗 GBM 抗体疾病不完全相同。Goodpasture 综合征可存在抗 GBM 抗体,也可不存在。有些存在抗GBM 抗体的肾炎又可不表现为 Goodpasture 综合征。GBM 是由蛋白质和葡萄糖氨基聚糖组成的结构。胶原是主要蛋白质成份,并主要是以前胶原形式存在的Ⅳ型胶原。Ⅳ型胶原上的羟赖氨酸-半乳糖-葡萄糖复合物可作为抗原。实验证明它可以与抗 GBM抗体疾病患者血清中或肾组织中的抗体起反应。用抗Ⅳ型胶原的抗体注射于兔子可引起肺出血和肾小球炎症。在19例 Goodpasture 综合征患者的血液中测得抗Ⅳ型前胶原抗体者有15例。在 GBM 中除胶原蛋白     

抗肾小球基膜肾炎合并膜性肾病

青年男性患者,临床表现急进性肾炎综合征伴大量蛋白尿、低蛋白血症,血清抗肾小球基膜(GBM)抗体阳性,肾活检组织学呈新月体肾炎合并膜性肾病,免疫病理IgG呈线状及颗粒状沉积于血管袢,电镜下见GBM上皮侧电子致密物沉积,最终诊断为抗GBM肾炎合并膜性肾病.     

抗肾小球基底膜非Goodpasture抗体的致病性

本文观察了肾小球基底膜(GRM)非Goodpasture抗体,即抗层连蛋白(Laminin)、抗硫酸肝素蛋白多糖(HSPG)、抗Ⅳ型胶原7S抗体对大鼠肾脏的致病性,结果示上述抗体对大鼠肾脏均有一定的致病性,如尿蛋白增加,肾小球细胞增生.肾小管上皮细胞空泡变性,间质炎性细胞浸润,部分足突融合等,尤以复合抗体注射组为显著.     

肾功能正常的抗肾小球基膜抗体相关疾病--附3例报道

目的 :了解肾功能正常的抗肾小球基膜 (GBM)抗体相关疾病的临床和病理特点。　 方法 :收集近 6年在我科确诊的 1 0 5例抗GBM抗体相关疾病患者的临床病理资料 ,对其中肾功能一直保持正常的患者重点分析 ,并应用间接免疫荧光法 (IIF)、酶联免疫吸附法 (ELISA)及免疫印迹法 (Western blotanalysis)检测及鉴定血清抗GBM抗体。　 结果 :1 0 5例患者中 3例 (2 86 % )肾功能一直保持正常 ,平均随访时间 2 2～ 57(40± 1 7 5)个月。均为青年男性。其中 2例表现为Goodpasture综合征 ,1例单纯表现为肺出血。 2例行肾活检 ,病理均为轻度系膜增生性肾小球肾炎 ,无新月体形成。直接免疫荧光和IIF均可见IgG沿肾小球毛细血管袢呈线样沉积。ELISA法检测血清抗GBM抗体均为阳性 ,Western blot法患者血清识别的蛋白条带与抗GBM抗体阳性对照一致。　 结论 :肾功能正常的抗GBM抗体相关疾病并不少见 ,我国对其认识尚不足。对有肺出血伴或不伴尿检异常的患者应考虑到该病可能 ,早期检测血清抗GBM抗体 ,可做到早期诊断 ,早期治疗。     

老年人肾小管间质性肾炎合并抗肾小球基底膜抗体阳性1例

肾小管间质性肾炎(TIN)是一种常见但易被忽视的临床病理综合征。抗肾小球基底膜(GBM)抗体阳性多见于急进性肾小球肾炎,其肾脏病理主要表现为新月体肾炎,两者均可表现为快速进展的肾功能不全,由于早期临床症状及指标变化不典型,常延误诊治甚至导致终末期肾脏病(ESRD)。现报道一例老年人抗GBM抗体阳性TIN的诊治过程,以期...     

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。     

肾小球基膜Ⅳ型胶原亚链定量分析在Alport综合征诊断中的意义

目的:通过对肾组织Ⅳ型胶原亚链免疫组化染色未见异常的Alport综合征 (AS)患者进行Ⅳ型胶原亚链构成比的定量分析,探讨不典型AS的发病机制,提高AS的诊断水平。　方法:选取临床、病理及电镜符合AS、但肾组织Ⅳ型胶原亚链染色未见异常的患者 14例,运用免疫荧光双套色法,通过激光共聚焦荧光显微镜定量分析肾小球基膜(GBM)Ⅳ型胶原中α3链、α5链的含量。并选取 4例薄基膜肾病及 10例肾活检病理诊断为轻度系膜增生性病变(MsPGN)患者的组织切片作为对照。　结果:入选的 14例患者在电镜下皆以GBM病变为主。通过定量分析GBMⅣ型胶原亚链构成比,我们发现,AS患者GBMα3链和α5链在Ⅳ型胶原总体分布中所占的比例明显减少(P<0. 05, P<0. 01vsMsPGN)。根据肾组织Ⅳ型胶原亚链构成比的不同,可以将这 14例患者分为三组:①2例患者α5链 /Ⅳ型胶原比值降低,α3链 /Ⅳ型胶原比值正常。这组患者男女各 1例,无明确家族史;②9例患者α3 /Ⅳ及α5 /Ⅳ比值同时降低。这组患者女性发病明显多于男性,家系分析显示遗传方式为X性连锁显性遗传。③3例患者α3 /Ⅳ及α5 /Ⅳ比值皆正常。这组患者男性 2例,女性 1例。家系分析显示遗传方式亦为X性连锁显性遗传。我们还发现,蛋白尿的发生与α5链 /Ⅳ型胶原比值的降低程度密切相关,存在     

抗肾小球基膜肾炎合并糖尿病肾病

中年男性,以持续肉眼血尿伴大量蛋白尿、肾功能减退、血抗肾小球基膜( GBM)抗体阳性起病；肾活检组织学符合新月体肾炎,免疫荧光见IgG沿肾小球毛细血管袢线性沉积,符合抗GBM肾炎,同时亦见肾小球呈结节样改变、肾小管基膜(TBM)增厚、动脉透明变性等,超微结构观察GBM呈均匀一致性增厚,经糖耐量检查确诊糖尿病.该患者最终诊断为抗GBM肾炎合并糖尿病肾病(DN).     

肾小球基膜自身抗体引起肾小球肾炎中吸烟与肺出血的关系

咯血合并肾小球肾炎称为肺出血-肾炎综合征(Goodpasture综合征),其中3/4病例伴有肾小球基膜(GBM)自身抗体。肺出血为何只在抗GBM肾炎中存在尚不清楚,本文提示在抗-GBM肾炎中肺出血的发生与吸烟有密切关系。研究对象为51例有肾小球肾炎的临床及形态学证据并出现抗-GBM抗体的患者,其中45例经肾活检诊断为抗-GBM病。男28例,女23例,年龄在4～72岁。肺出血的诊断标准:咯血;或无咯血者至少符合以下3项标准中的2项即胸片示特征性的肺泡阴影,24小时内血红蛋白浓度下降至少2g/dl而无其他原因;单次呼吸一氧化碳常数(KCO)从原来的稳定水平急性升高至少30％。     

肾小球肾炎发病机理研究的若干进展

肾炎免疫发病学说在60年代已得到公认,根据实验研究及临床观察,将肾炎区分为抗肾抗体型(抗肾小球基底膜型)及免疫复合物型两大类。前者是由于抗体存在着抗肾小球基底膜(glomerular basement membrane,GBM)的     

Coexistence of Anti-Glomerular Basement Membrane Antibodies and Anti-Neutrophil Cytoplasmic Antibodies in a Child With Human Leukocyte Antigen Susceptibility and Detailed Antibody Description: A Case Report

Anti-glomerular basement membrane (anti-GBM) disease and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis both could cause rapidly progressive glomerulonephritis. The coexistence of ANCAs and anti-GBM antibodies was known as “double positive,” which was extremely rare in children. We report a pediatric case with coexistence of ANCAs and anti-GBM antibodies.A 6-year-old girl presented with acute renal failure, hematuria, proteinuria, and oliguria. She was double positive of ANCAs specific to myeloperoxidase, and anti-GBM antibodies. Kidney biopsy confirmed linear immunoglobulin (Ig)G deposit along GBM and 100% of crescent formation in glomeruli; among them 83.3% were cellular crescents. Human leukocyte antigen (HLA) gene typing showed DRB1∗1501, an allele strongly associated with anti-GBM disease, and DRB1∗0405, an independent risk factor for renal failure in patients with ANCA-associated vasculitis. The titer of anti-GBM antibodies was 1:800, and the predominant IgG subclass was IgG1, which was closely related with severe kidney injury and worse outcome. The target antigen of anti-GBM antibodies was restricted on the noncollagen domain 1 of the α3 chain of type IV collagen (α3[IV]NC1), with recognitions to both epitopes, E_A (α3_17–31) and E_B (α3_127–141).This is the first reported pediatric case with coexistence of ANCAs and anti-GBM antibodies, in which the HLA typing and immunologic characters of autoantibodies were identified. The findings on this early-onset patient are meaningful for understanding the mechanisms of both anti-GBM disease and ANCA-associated vasculitis.     

Circulating anti-glomerular basement membrane antibodies in coeliac disease and epidermolysis bullosa acquisita

Abstract The demonstration of circulating anti-glomerular basement membrane (GBM) antibodies is almost diagnostic for anti-GBM disease and Goodpasture's syndrome. These antibodies are, however, occasionally present in SLE and diabetes, in association with IgA disease and membranous nephropathy and after transplantation in Alport's syndrome. In addition, we describe circulating anti-GBM antibodies in a research worker who handled GBM and in whom coeliec disease later developed, and in an individual with epidermolysis bullosa acquisita. Neither patient had impaired renal function nor an abnormal urinary sediment, suggesting either that these antibodies were of low affinity, or that additional factors are required for the pathogenesis of an aggressive glomerular lesion when circulating anti-GBM antibodies are present. In at least one of these individuals anti-GBM antibodies may have developed after the exposure of basement membrane collagen type IV to activated immunological mediators and cells. (Aust NZ J Med 1991; 21: 867–870.)     

Circulating autoantibodies as serological markers in the differential diagnosis of pulmonary renal syndrome

Abstract. Objectives . Pulmonary renal syndrome (lung haemorrhage and glomerulonephritis) is a fulminant condition that warrants a rapid diagnosis and treatment to prevent mortality and preserve renal functions. However, the patients frequently present with non-specific pulmonary symptoms in the early phase of the syndrome and the diagnosis is often missed. Recently, several autoantibodies have been described in association with various forms of glomerulonephritis. We evaluated the association as well as the diagnostic and the prognostic significance of these antibodies in pulmonary renal syndrome. Design . Retrospective clinical study. Setting . University Hospital. Subjects . Forty consecutive patients with biopsy verified glomerulonephritis and overt haemoptysis or pulmonary infiltrates compatible with lung haemorrhage. Interventions . Analysis of proteinase 3 antineutrophil cytoplasm antibodies (PR3-ANCA), myeloperoxidase (MPO)-ANCA, antiglomerular basement membrane (GBM) and anti-entactin antibodies. Results . Thirty-six (90%) patients possessed one or more autoantibodies. Twenty-seven (70%) patients had ANCA (PR3-ANCA, MPO-ANCA or both). The remaining positive patients (n = 9) had anti-GBM antibodies. Only two patients had anti-entactin antibodies, suggesting a poor association of these antibodies with PRS. The majority of patients with anti-GBM antibodies had a very poor clinical outcome (five irreversible renal failure; three deaths). On the other hand, despite no significant difference in clinical features or renal morphology from patients with anti-GBM antibodies, 19 patients (70%) with ANCA recovered completely following treatment. Conclusions . Our study demonstrated that the presence of autoantibodies is a predominant feature of PRS and that the type of immunologic injury is of paramount importance in determining the course of illness in this syndrome. Analysis of the aforementioned antibodies can help in an early differential diagnosis and thus, in better management of PRS.     

免疫组化检测Alport患者基底膜Ⅳ型胶原α链分布

为了观察Ⅳ型胶原各链在Ａｌｐｏｒｔ综合征（ＡＳ）患者基底膜上分布，初步探讨ＡＳ的发病机制，评估间接免疫荧光法检测Ⅳ型胶原对ＡＳ的诊断价值，采用针对Ⅳ型胶原α１、３、４、５链ＮＣ１片段的特异性单克隆抗体，利用间接免疫荧光技术对Ⅳ型胶原在８例Ａｌｐｏｒｔ患者的肾（６例）及皮肤（５例）基底膜上的分布进行了检测。结果显示：４例Ｘ伴性显性（ＸＤ）遗传男性Ａｌｐｏｒｔ患者肾小球基底膜上有α３、４、５（Ⅳ）链共同缺失，表皮基底膜上α５（Ⅳ）链间接免疫荧光亦为阴性，而３例常染色体显性及１例常染色体隐性遗传的Ａｌｐｏｒｔ患者间接免疫荧光均为阳性，与正常结果相同。提示ＡＳ存在Ⅳ型胶原生化组成异常，ＸＤ－ＡＳ的发病与Ⅳ型胶原α５链的生成异常有关；皮肤及肾组织Ⅳ型胶原α链间接免疫荧光检测对ＸＤ－ＡＳ具重要诊断意义。     

Clinical significance of anti-nucleolar antibodies detected by immunoprecipitation method in patients with systemic sclerosis]

We have characterized a clinical significance of anti-U3RNP, anti-7-2RNP, anti-RNA polymerase I and anti-PM-Scl antibody, autoantibodies to nucleolar proteins detected by immunoprecipitation method in patients with systemic sclerosis (SSc). In 248 patients with SSc, anti-U3RNP antibody was positive in 9 (3.6%), anti-7-2RNP antibody was positive in 7 (2.8%) and anti-RNA polymerase I antibody was positive in 3 (1.2%). But none of 248 patients was positive for anti-PM-Scl antibody. Anti-U3RNP antibody positive SSc patients showed significantly lower frequency of joint and lung involvements, compared with anti-U3RNP antibody negative SSc patients. Anti-7-2RNP antibody was found only in patients with limited scleroderma. The anti-7-2RNP antibody could be detected before appearance of skin thickening, so this indicate the usefulness of detecting anti-7-2RNP antibody in the early stage of SSc. Two of 3 anti-RNA polymerase I antibody positive patients were classified as diffuse scleroderma. All anti-RNA polymerase I antibody positive patients had high incidence of internal organ involvements including lung, heart and kidney, so two of these patients died of heart failure. These data showed the close clinical association of antigenic specificities of anti-nucleolar antibodies analysed by immunoprecipitation method, and indicated the usefulness of detecting these anti-nucleolar antibodies in subgrouping of patients with SSc.     

Addition of angiotensin II type 1 receptor blocker to CCR2 antagonist markedly attenuates crescentic glomerulonephritis

The monocyte chemoattractant protein-1 (MCP-1)/CC-chemokine receptor 2 (CCR2) pathway plays a critical role in the development of antiglomerular basement membrane (anti-GBM) nephritis. We recently showed angiotensin II (Ang II) infusion in rats activated MCP-1 and transforming growth factor-β1 (TGF-β1), which in turn induced macrophage infiltration of renal tissues. This study was performed to demonstrate that combination therapy with a CCR2 antagonist (CA) and an Ang II type 1 receptor blocker (ARB) ameliorated renal injury in the anti-GBM nephritis model. An anti-GBM nephritis rat model developed progressive proteinuria and glomerular crescent formation, accompanied by increased macrophage infiltration and glomerular expression of MCP-1, angiotensinogen, Ang II, and TGF-β1. Treatment with CA alone or ARB alone moderately ameliorated kidney injury; however, the combination treatment with CA and ARB dramatically prevented proteinuria and markedly reduced glomerular crescent formation. The combination treatment also suppressed the induction of macrophage infiltration, MCP-1, angiotensinogen, Ang II, and TGF-β1 and reversed the fibrotic change in the glomeruli. Next, primary cultured glomerular mesangial cells (MCs) stimulated by Ang II showed significant increases in MCP-1 and TGF-β1 expression. Furthermore, cocultured model consisting of MCs, parietal epithelial cells, and macrophages showed an increase in Ang II-induced cell proliferation and collagen secretion. ARB treatment attenuated these augmentations. These data suggest that Ang II enhances glomerular crescent formation of anti-GBM nephritis. Moreover, our results demonstrate that inhibition of the MCP-1/CCR2 pathway with a combination of ARB effectively reduces renal injury in anti-GBM nephritis.     

检测慢性丙型肝炎患者抗－HCVIgM的临床意义

对８２例输血后慢性丙型肝炎病人丙型肝炎病毒抗体（抗－ＨＣＶ）ＩｇＭ动态变化进行观察，８２例患者均检测到抗－ＨＣＶ抗体，其中５１例抗－ＨＣＶＩｇＭ阳性。抗－ＨＣＶＩｇＭ出现规律表现为４种类型：（１）持续检出型２４例（２９．２７％）；（２）间断检出型８例（９．７６％）；（３）短暂检出型１９例（２３．１７％）；（４）阴性型３１例（３７．８０％）。将８２例输血后慢性丙型肝炎抗－ＨＣＶＩｇＭ出现类型与丙氨酸转氨酶（ＡＬＴ）、ＨＣＶＲＮＡ消长情况比较，发现阴性型具有较低的ＡＬＴ峰值，而其它３型ＡＬＴ峰值较高（Ｐ＜０．０１）。８例经干扰素治疗的慢性活动性丙型肝炎患者，治疗前均有ＡＬＴ明显异常及ＨＣＶＲＮＡ、抗－ＨＣＶＩｇＭ阳性，治疗后１～３个月ＡＬＴ均转为正常，ＨＣＶＲＮＡ转为阴性，但其中只有３例伴抗－ＨＣＶＩｇＭ的阴转，随访１年发现，只有抗，ＨＣＶＩｇＭ阴转的３例病人得以痊愈，其余５例均在治疗后半年内病情复发。提示治疗中伴有抗－ＨＣＶＩｇＭ阴转的患者预后良好。     

Characteristics and outcome of crescentic glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody

A subset of patients with crescentic glomerulonephritis (CGN) is characterized serologically by the presence of antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane antibody (anti-GBM) called “double positive” disease. The clinical significance of the occurrence of both antibodies is not clear. This study aims to describe the clinical and histologic characteristics and outcomes of CGN in a US cohort of double positive (DP) patients and compare them to patients with anti-GBM disease only or ANCA only (ANCA-associated vasculitis (AAV)). Renal biopsies with a diagnosis of CGN with either pauci-immune or linear immunofluorescence were selected and classified as AAV, anti-GBM disease, or DP based on serologic testing at the time of biopsy. Data on demographics, clinical presentation, treatment, and outcome were obtained by chart review. Six patients with anti-GBM disease, 9 with DP disease, and 18 AAV patients matched for year of diagnosis with DP were identified. Extrarenal disease manifestations were more prominent in the DP patients. The DP patients had severe renal dysfunction at presentation with eight of nine patients requiring dialysis at presentation. Renal biopsy findings of DP patients were similar to anti-GBM disease with majority of glomeruli showing cellular crescents. Eighty-nine percent of patients were treated with immunosuppressive therapy and 78 % with plasmapheresis. At 1 year, all nine DP patients reached end-stage renal disease. We conclude that the DP patients share extrarenal manifestations similar to AAV patients while the renal manifestations resemble anti-GBM patients clinically and histologically. The renal prognosis of DP patients remains poor despite treatment.