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1.
Polyoma nephropathy is an increasingly prevalent complication in kidney transplant recipients. We identified tubular basement membrane immune complexes in allograft recipients with polyoma nephropathy. To evaluate this lesion, biopsies demonstrating polyoma infection over a 2-year period were assessed for the presence, localization, and composition of tubular basement membrane immune complexes including simian virus 40 (SV40) antigen and for histologic classification according to Drachenberg. Charts were reviewed for clinical information. Thirteen of 26 biopsies from 11 of 20 patients demonstrated tubular basement membrane immune complexes, all of which contained C3, immunoglobulin G, and SV40 antigen. Deposits were in all nephron segments associated with tubular cell viral infection and tubulointerstitial inflammation; no SV40 antigen was in glomeruli. The Drachenberg histologic classification tended to be more advanced in biopsies with tubular basement membrane immune complexes, but not significantly so. There were no differences in patients with and without immune complexes with respect to age, sex, time after engraftment, and plasma viral load. Tubular basement membrane immune complexes were present in 5 of 6 patients who lost renal function and in 5 of 12 with currently functioning grafts (P < .1). Polyoma-associated tubular basement membrane immune complexes seem to be a local phenomenon, likely related to viral antigen shedding. The clinical significance is uncertain but may portend a worse prognosis.  相似文献   

2.
The target antigen, a 54-kD glycoprotein (gp54), reactive with sera from patients with anti-tubular basement membrane (anti-TBM) nephritis, was isolated from collagenase-digested (CD) bovine TBM. The purified gp54 was shown to be non-collagenous by amino acid analysis, and to be a unique basement membrane component by amino-terminal sequencing. The nephritogenicity of gp54 was demonstrated by immunizing strain XIII guineapigs with purified gp54, and producing anti-gp54 antibody and tubulo-interstitial nephritis. Anti-gp54 antibody, affinity-purified from sera of patients with anti-TBM nephritis, bound by immunoblotting to 54-kD and, to a lesser extent, 48-kD components of partially purified human CD-TBM. Indirect immunofluorescence showed that gp54 was present in the basement membrane of proximal tubules of the kidneys of normal human, cow, rabbit, guineapig and Brown-Norway rat but not in Lewis rat. Immunoelectron microscopy revealed localization of gp54 along the interstitial side of the TBM and its association with interstitial collagen fibres. These results indicate that gp54 is the nephritogenic antigen involved in tubulo-interstitial nephritis, and is unique in chemical characteristics and localization in the kidney.  相似文献   

3.
A 70‐year‐old Japanese man with diabetes mellitus was referred to our hospital for treatment of renal dysfunction. Renal biopsy revealed that the tubular basement membrane (TBM) showed extreme thickening histologically, and selective polyclonal immunoglobulin G deposition on the thickened TBM, whereas no immunoglobulin deposition was found in the glomeruli in an immunofluorescence study. In electron microscopy, a powdery type of electron dense material, which was similar to that seen in Randall‐type monoclonal immunoglobulin deposition disease (MIDD), was observed on the tubular epithelial side of the TBM. However, the present case was differentiated from MIDD, because polyclonal deposition with both kappa and lambda deposition on the TBM was observed. Moreover, there was no noticeable glomerular deposition, which is usually found in cases of MIDD. Anti‐TBM disease was also considered as a differential diagnosis, in which polyclonal immunoglobulin deposits selectively on the TBM. However, in the present case, prominent interstitial nephritis was not observed. A similar case with a history of diabetes mellitus has been reported, which was diagnosed as Polyclonal Immunoglobulin G Deposition Disease. No further reports of this case have emerged thereafter; we present this case as the second report supporting this article.  相似文献   

4.
The penetration into the glomerular basement membrane of anionic and cationic ferritin has been studied in rats made proteinuric by intraperitoneal administration of bovine serum albumin. In comparison with control animals anionic ferritin penetrated the glomerular basement membrane to a much greater extent in proteinuric rats. Some ferritin particles were observed in small invaginations of the epithelial cell membrane adjacent to the glomerular basement membrane and incorporated in pinocytotic vesicles within the epithelial cell cytoplasm. This was not seen in control animals. Cationic ferritin distribution in the glomerular basement membrane was similar in control and proteinuric rats suggesting that the increased anionic ferritin penetration observed occurs without any reduction in fixed anionic charge.  相似文献   

5.
The aim of this work was to determine the mean glomerular basement membrane (GBM) thickness in the Saudi population. We calculated the average GBM thickness in patients diagnosed with minimal change disease, and the ultrastructural analysis of at least three glomeruli was reviewed using a digital camera installed in an electron microscope. There were a total of 53 cases from 53 Saudi patients aged 2–70 years old. The mean GBM thickness for all cases was 323.6 ± 49.5 nm. There was no significant statistical difference in the mean GBM thickness between males and females. There were significant differences in the mean GBM thickness between all age groups, except for between the age groups 18–60 and >60 years old, where GBM thickness did not differ significantly. Age was significantly correlated with definite progression or diminution in the thickness of the GBM. The mean GBM thickness in our Saudi sample population was comparable to the very few reported measurements in the literature. There was no significant association between GBM thickness and gender; however, GBM thickness is directly proportional to age, up to 60 years old.  相似文献   

6.
选用兔肾小管基底膜(TBM)、完全福氏佐剂及百白破疫苗免疫雌性Wistar大鼠,成功地建立了肾小管间质性肾炎(TIN)模型。实验证明在TIN发生时,TBM上有IgG和C3沉积,肾间质大量单个核细胞浸润,主要是淋巴细胞,部分有肉芽肿形成。随后出现肾小管萎缩和肾间质纤维化。用环磷酰胺可以抑制TIN的发生和进展,其作用机制可能是抑制细胞免疫反应  相似文献   

7.
In this investigation it has been found that naturally-occurring (i.e. indigenous, not transplanted) tumours of diverse organs in a spectrum of vertebrates from frogs to man can secrete enzymes which degrade basement membrane collagens (types IV and V). The enzymes are inhibited by chelating agents (EDTA) but not by other protease antagonists and are, therefore, specific metalloproteases. Individual tumours do not necessarily secrete collagenases active against all collagen types (I, IV and V) and release of these different enzymes does not, therefore, appear to be coordinated. These biochemical findings support those reported for serially transplanted tumour cell lines and provide a plausible mechanism for the destruction of basement membranes and stromal collagen fibres observed morphologically in tumour spread.  相似文献   

8.
Specificity of basement membrane thickening in severe asthma   总被引:1,自引:0,他引:1  
BACKGROUND: Reticular basement membrane (RBM) thickness is considered a hallmark for airway remodeling in airway diseases such as asthma. It is still unclear whether this measurement could be associated with disease severity or apply to chronic obstructive pulmonary disease (COPD). A wide range of results, at baseline or after therapeutic intervention, have been reported using different measurement methods. OBJECTIVE: To determine whether increased RBM thickness could be associated specifically with severe asthma and in COPD in large samples. METHODS: We blindly measured RBM thickness in endobronchial biopsies from 50 patients with severe asthma (mean age, 53 years; FEV(1) 66% predicted, inhaled steroids > or =1500 microg and 20 mg daily dose of oral corticosteroids, lifelong nonsmokers), 50 untreated patients with mild asthma (mean age, 33 years; FEV(1) 93%pred, lifelong nonsmokers), 50 patients with COPD (mean age, 57 years; FEV(1) 53%pred, all current smokers), and 18 control subjects using 2 different validated quantitative and computer-assisted methods (repeated multiple point-to-point vs area by length ratio). RESULTS: Reticular basement membrane thickness was higher in severe asthma compared with mild asthma and COPD (P = .0053). On the basis of receiver operating characteristic curves, RBM thickness was effective in differentiating severe asthma from other groups (sensitivity and specificity, 98% and 95%, respectively, above a threshold of 5 microm vs control, 70% and 75% at 7 microm vs mild, 83% and 68% at 6 microm vs COPD). CONCLUSION: Increased RBM thickness was specifically associated with severe asthma, whereas surprisingly, COPD and mild asthma had similar remodeling features. CLINICAL IMPLICATIONS: Reticular basement membrane thickness can be considered a hallmark of severe asthma.  相似文献   

9.
The presence and distribution of anionic sites in the glomerular basement membrane and visceral epithelial cell coat has been demonstrated. No definite decrease in intensity or periodicity of staining of basement membrane particulate sites was seen in protein overload proteinuric animals and only one staining technique employed for electron microscopy (alcian blue 8GX) demonstrated a focal decrease in visceral epithelial cell coat staining in severely damaged glomeruli. A decrease in overall glomerular staining was also demonstrated by quantitative analysis of colloidal iron staining by light microscopy. The findings differ from those described in puromycin aminonucleoside nephropathy and nephrotoxic nephritis. Staining was demonstrated also in other basement membranes, in Bowman's capsule and along interstitial collagen fibres.  相似文献   

10.
The basement membrane as an antigenic structure in autoimmune diseases has been a matter of controversy. The purpose of our study was to determine possible structural changes in the follicular basement membrane (FBM) in thyroid autoimmune and non-autoimmune diseases. Immunohistochemical staining for collagen IV and laminin showed that the continuity of the FBM was preserved in toxic adenoma (three cases), atoxic multinodular goiter (nine cases) as well as in autoimmune disease. Integrity of the FBM was observed in all 11 cases of Graves' disease and Hashimoto's thyroiditis (seven cases) studied. In some instances, the FBM was thinned in areas of contact with inflammatory infiltrate. We conclude that the auto-antibodies, and possibly other factors present in autoimmune thyroid diseases, do not significantly alter the integrity of the FBM.  相似文献   

11.
12.
不同浓度基底膜组份对雪旺细胞生长的影响   总被引:1,自引:1,他引:1  
目的:了妥不同浓度的基底膜成分对体外培养雪旺细胞生长的影响。方法:用不同浓度的基底膜成分修饰培养板底,并设置空白对照,将纯化的雪旺氏细胞以相同数量接种至各组孔内;观察细胞生长.培养72h后以MTT法和3H-TdR掺入法检测各组细胞的增殖情况,数据进行统计学分析。结果:层粘连蛋白,纤维粘连连蛋白和IV型胶原促雪旺细胞分裂增殖的最低浓度分别是:10μg/ml、10μg/ml、3μg/ml;发挥最大促进效应的浓度分别是:500μg/ml,300μg/ml和100μg/ml。结论:不同的基底膜组份和修饰浓度对雪旺细胞分裂增殖所发挥的作用强度不同,本实验为组织工程化神经桥接体的优化修饰提供了实验基础。  相似文献   

13.
目的研究抗肾小球基底膜(GBM)抗体的抗原决定簇及其与临床病理表现的关系。方法用辣根过氧化物酶标记的亲和层析纯化的抗GBM自身抗体(APab-HRP)和抗α1、3、5(IV)NC1单克隆抗体(Mab1、3、5)作为识别GBM上不同抗原决定簇的探针,应用竞争性ELISA法测定抗GBM抗体的抗原决定簇。结果59例患者中,58(98.3%)例可抑制Mab3,20(33.9%)例可抑制Mab1,均不抑制Mab5。同一血清对APab.HRP和对Mab3的抑制率呈平行关系(P〈0.01)。不同患者血清抗体对APab.HRP的抑制率与该患者确诊时的血肌酐浓度呈正相关(P〈0.05)。出现少尿或无尿的患者血清抗体对APab-HRP的抑制率较高(P〈0.01)。单纯抗GBM抗体阳性组较合并ANCA阳性组对APab.HRP的抑制率较高(P〈0.05)。是否出现咯血、肾脏病理新月体所占比例、肾转归以及其他临床表现不同的患者,对各种探针的抑制率均无差异。结论抗GBM抗体的主要抗原决定簇位于α3(IV)NC1,但并不完全一致。抗原决定簇的差异可能与肾损害的程度相关。  相似文献   

14.
The thickness of the perineurial cell basement membrane was examined in diabetic and non-diabetic human sural nerve. A significant increase in thickness was found in the diabetic group. The nature of this thickening was investigated using immunohistochemistry and image analysis in order to semi-quantify three of the major intrinsic components of the perineurial cell basement membrane: collagen IV, laminin and fibronectin. Amounts of all three components were shown to be increased in the diabetic group, but not significantly so. However, significant linear correlations between fascicle size and perineurial collagen IV, laminin and fibronectin were identified in both diabetic and non-diabetic nerve.  相似文献   

15.
目的 制备人抗肾小球基底膜(GBM)抗体的特异性人源化单链可变区抗体.方法 采用噬菌体表面展示技术,获得一个与人抗GBM抗体结合活性较强的单链可变区抗体片段的阳性克隆,并对该克隆进行DNA序列测定分析.结果 对噬菌体单链可变区抗体库经过3轮筛选后,与第1轮相比富集了137倍.噬菌体抗体与人抗GBM抗体的结合活性其中有35株克隆ELISA的吸光度较高.对这些噬菌体抗体进行交叉反应后,确定其中有10株交叉反应较弱.确定1株(C31)阳性克隆提取质粒,进行DNA序列测定,大小为750 bp,并符合人源化单链可变区抗体的序列结构.结论 应用噬菌体展示技术成功获得人-抗GBM抗体的单链可变区抗体基因,为临床上治疗Goodpasture综合征奠定实验基础.  相似文献   

16.
 目的 观察抗肾小球基底膜(GBM)病患者肾小球足细胞钙调神经蛋白(CaN)的表达,了解其与临床病理特点及肾脏长期存活的关系。方法 选取临床病理资料完整的抗GBM病患者29例,对照为8例肾小球轻微病变患者。收集患者临床资料,免疫组化方法检测CaN A亚基α亚单位(CnAα)在肾小球的表达,免疫荧光染色观察足细胞骨架蛋白synaptopodin表达,分析CnAα与临床病理表现及预后的关系。结果 29例抗GBM病患者肾小球内均有不同程度的CnAα表达阳性,阳性区域占肾小球面积百分比显著高于轻微病变者(21.63%±14.27% vs 2.21%±1.41%,p<0.01),同时伴有synaptopodin缺失。CnAα的表达量与抗GBM抗体峰值、血肌酐水平、血红蛋白水平、新月体比例及细胞/细胞纤维新月体比例呈现显著相关性,并与预后相关。结论 首次观察到抗GBM病患者肾小球内CnAα表达增强,表达量与疾病活动、严重程度及预后相关,提示足细胞可能参与抗GBM病新月体形成,其作用机制仍有待进一步研究。  相似文献   

17.
Monoclonal tubular basement membrane immune deposits (TBMID) are associated with progression of interstitial injury in renal allograft. However, the significance of monoclonal and polyclonal TBMID in the native kidney remains unclear. We retrospectively analyzed 1894 native kidney biopsies and 1724 zero-hour biopsies performed between 2008 and 2018 in our institution. The rate of immunoglobulin G (IgG) TBMID was found to be 8.4% among native kidney biopsies and 0.4% among zero-hour biopsies. Polyclonal TBMID is common in IgG4-related tubulointerstitial nephritis (37.5%), diabetic nephropathy (31.3%) and lupus nephritis (25.5%). Monoclonal IgG TBMID was identified in seven cases, including three zero-hour biopsies. The combination of IgG1κ was observed in two cases, IgG1λ in three, and IgG2κ in two. Electron microscopy revealed powdery electron-dense deposits in all cases. Monoclonal gammopathy of undetermined significance was diagnosed in one case. Although one patient with focal segmental glomerulosclerosis developed renal failure, all others exhibited stable renal function. Monoclonal IgG TBMID in the native kidney is not associated with renal prognosis. However, this may be an interesting immunopathological finding that would help clarify the pathogenesis of TBM immune deposits. Further study for both monoclonal and polyclonal TBMID is required in the future.  相似文献   

18.
A quantitative study of glomerular basement membrane (GBM) changes in 16 cases of IgA nephropathy was carried out on two whole glomeruli per case using a wide-field electron microscope. We found that GBM changes are observed more frequently than previously reported, although some changes are small and uneven in distribution. Changes include (a) attenuation, (b) lytic attenuation, (c) garland-shaped widening of the GBM, (d) dome-shaped widening of the GBM, and (e) disruption of the GBM. There was some correlation between the severity of light microscopic findings and the percentage of GBM affected by complicated changes ((b)-(e)). The percentage of complicated GBM changes correlated with the amount of proteinuria at biopsy. The frequent occurrence of GBM changes in IgA nephropathy suggests that they might be playing a role in the pathogenesis of IgA nephropathy.  相似文献   

19.
Summary To elucidate the morphological basis of glomerular haematuria, morphometric analysis of the glomerular basement membrane (GBM) and lamina densa (LD) was performed on silver impregnated samples for electron microscopy. The cases studied consisted of 3 groups: group A, normal controls, being from donors for kidney transplantation; group B, haematuric; and group C, non-haematuric cases with isolated proteinuria. Qualitative analysis revealed that gap formation, splitting, segmental and diffuse thinning of the GBM occur preferentially in haematuric cases. The morphometry of the GBM and LD yielded increased mean values of the GBM and of LD thickness in groups B and C. The coefficient of variation (CV, SD/mean) for the GBM and LD, however, was the highest in group B among the 3 groups, suggesting the most irregular GBM and LD in group B. In addition, CV was significantly higher in cases with splitting, segmental attenuation and gap of the GBM than cases without. The findings suggest that the irregularity of the GBM rather than its mean thickness is clearly associated with splitting and ultimately with haematuria via the gaps produced.  相似文献   

20.
Peroxisome proliferator-activated receptor alpha (PPARalpha) ligands are medications used to treat hyperlipidaemia and atherosclerosis. Increasing evidence suggests that these agents are immunosuppressive. In the following studies we demonstrate that WY14,643, a PPARalpha ligand, attenuates expression of anti-glomerular basement membrane disease (AGBMD). C57BL/6 mice were fed 0.05% WY14,643 or control food and immunized with the non-collagenous domain of the alpha3 chain of Type IV collagen [alpha3(IV) NC1] in complete Freund's adjuvant (CFA). WY14,643 reduced proteinuria and greatly improved glomerular and tubulo-interstitial lesions. However, the PPARalpha ligand did not alter the extent of IgG-binding to the GBM. Immunohistochemical studies revealed that the prominent tubulo-interstitial infiltrates in the control-fed mice consisted predominately of F4/80(+) macrophages and WY14,643-feeding decreased significantly the number of renal macrophages. The synthetic PPARalpha ligand also reduced significantly expression of the chemokine, monocyte chemoattractant protein (MCP)-1/CCL2. Sera from mice immunized with AGBMD were also evaluated for antigen-specific IgGs. There was a significant increase in the IgG1 : IgG2c ratio and a decline in the intrarenal and splenocyte interferon (IFN)-gamma mRNA expression in the WY14,643-fed mice, suggesting that the PPARalpha ligand could skew the immune response to a less inflammatory T helper 2-type of response. These studies suggest that PPARalpha ligands may be a novel treatment for inflammatory renal disease.  相似文献   

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