IgA肾病肾组织纤连蛋白的表达

目的：探讨肾组织纤连蛋白的表达在ＩｇＡ肾病（ＩｇＡＮ）进展中的病理学及临床意义。方法：运用Ｓ－Ｐ法对６０例ＩｇＡＮ的肾活检标本进行纤连蛋白（ＦＮ）、增殖细胞核抗原（ＰＣＮＡ）的免疫组化染色，并与肾小球及肾小管间质损伤程度相对照，进行统计学处理。结果：肾小球系膜区ＦＮ与系膜细胞增生、肾小球损伤程度及肾小管间质损伤程度均呈正相关。基膜ＦＮ的出现与基膜内皮下沉着物、肾小球损伤程度及肾小管间质损伤程度均密切相关。结论：肾小球系膜区ＦＮ可作为肾活检组织病理中肾小球系膜的标志，尤其是基膜ＦＮ的聚集增多，是判断ＩｇＡＮ进展和预后不良的可靠指标     

IgA肾病组织纤连蛋白的表达

目的：探讨肾组织纤维蛋白的表达在ＩｇＡ肾病（ＩｇＡ Ｎ）进展中的病理学及临床意义。方法：运用Ｓ－Ｐ法对６０例ＩｇＡ Ｎ的肾活检示本进行纤维蛋白（ＦＮ）、增殖细胞核抗原（ＰＣＮＡ）的免疫组化染色，并与肾小球及肾小管间质损伤程度相对照，进行统计学处理。结果：肾小球系膜区ＦＮ与系膜细胞增生、肾小球损伤程工及肾小管间质损伤程度均呈正相关。基膜ＦＮ的出现与基膜内皮下沉着物、肾小球操作程度及肾小管间质损伤程度     

IgA肾病的临床病理研究

IgA肾病研究发现,免疫复合物不仅可沉积在系膜区,也可沉积在内皮下,甚至上皮下,并有相应的基底膜损伤,肾小球系膜增殖及组织损伤程度与临床表现、实验室检查有一定的内在联系,而与荧光的强弱及免疫球蛋白类型无关。雷公藤多甙对其治疗有一定的疗效。     

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     

乙型肝炎肝硬化肾脏损害的免疫病理与临床关系探讨

对乙型肝炎肝硬化尸检１２例肾脏病理与免疫病理进行观察，免疫病理发现在肾小球的内膜和系膜区有乙型肝炎病毒抗体ＩｇＭ、ＩｇＡ、ＩｇＧ和免疫复合物Ｃ３、Ｃｌｑ沉积，只发现１例有ＨＢｓＡｂ阳性。提示可能肾脏损害与ＨＢＶ直接作用的关系不大，而作为抗原引起体液免疫或通过循环免疫复合物沉积与肾病变关系较密切。     

膜性肾病合并IgA肾病的临床病理特点

目的探讨膜性肾病合并IgA肾病的临床病理特点。方法回顾性研究北京大学第一医院肾内科和北京大学肾脏病研究所1998年1月—2006年4月问的肾活检病例9572例,对11例膜性肾病合并IgA肾病的临床病理特点进行分析,结合免疫电镜标记方法,对其病理诊断及发病机制进行探讨。结果11例患者以中年为发病高峰,平均年龄39．9岁,女性多于男性（男：女为1：2．9）,临床表现为蛋白尿,其中7例（63．6％）出现肾病综合征水平的蛋白尿,7例（63．6％）合并镜下血尿,肾功能均正常,除外了肝炎病毒感染、系统性红斑狼疮等继发性疾病。光镜下可见肾小球基底膜空泡变性和增厚,系膜细胞和基质轻度增生,2例可见少数肾小球伴有新月体形成。免疫荧光检查见IgG和c3颗粒样沿肾小球毛细血管壁沉积;IgA团块状在肾小球系膜区沉积。电镜检查可见肾小球上皮细胞下多数块状电子致密物沉积,系膜区可见团块状电子致密物沉积。免疫电镜标记结果显示,IgG定位于肾小球上皮细胞下的电子致密物,IgA定位于肾小球系膜区的电子致密物。结论膜性肾病合并IgA肾病兼具有膜性肾病和IgA肾病的临床病理特点,其发生过程可能为各自独立发生的两种疾病的叠加所致。     

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。     

粘附分子选择素在IgA肾病中变化的临床意义

目的：为探讨ＩｇＡ肾病患者血和肾组织中Ｐ选择素必变与疾病的关系。方法：采用酶联免疫吸附法、免疫组化及原位杂交技术检测了４５例ＩｇＡ肾病患者血浆和肾组织中Ｐ选择素含量及表达水平。结果：ＩｇＡ肾病患者血浆Ｐ选择素含量明显高于正常人,其中肾病综合征组和肾功能减退组含量又较肉眼血尿组、尿检异常组和肾炎综合征组显著增高造反素在患者肾组织中广泛表达,其中在Ⅳ级和Ⅴ级ＩｇＡ肾病肾小球中表达水平明显高于Ⅱ级和Ⅲ级     

单克隆丙种球蛋白病14例骨髓和肾脏活检病理分析

目的 探讨单克隆丙种球蛋白病患者骨髓和肾脏活检病理学特征。方法 回顾性分析14例单克隆丙种球蛋白病患者的骨髓和肾脏活检病理资料,并复习相关文献。结果 14例患者中,2例为多发性骨髓瘤合并轻链管型肾病(light chain cast nephropathy, LCCN):黏稠伴裂纹管型沉积于肾小管伴单核细胞反应、肾小管上皮细胞损伤和肾小管基底膜破裂;1例为意义未明的单克隆丙种球蛋白病(monoclonal gammopathy of unknown significance, MGUS)合并膜性肾病：大量免疫复合物沉积于肾小球上皮下和基底膜内;11例为有肾脏意义的单克隆丙种球蛋白病(monoclonal gammopathy of renal significance, MGRS):包括增生性肾小球肾炎伴单克隆丙种球蛋白沉积(proliferative glomerulonephritis with MIg deposits, PGNMID)2例：肾小球表现为系膜毛细血管增生性肾炎,免疫荧光及电镜显示单克隆丙种球蛋白沉积于系膜区、内皮下,淀粉样变性肾病9例：肾小球系膜区、血管壁呈现均质...     

细胞间粘附分子－1在非IgA系膜增殖性肾小球肾炎病变中表达的定量分析

应用免疫组化方法及计算机图象分析系统，检测了非ＩｇＡ系膜增殖性肾小球肾炎患者肾组织病变过程中细胞间粘附分子－１的变化。结果显示：在系膜细胞增殖的肾小球内细胞间粘附分子－１含量增加，并随病变进展明显增加，且与系膜细胞增殖程度显著正相关。     

Single light chain subclass (kappa chain) immunoglobulin deposition in glomerulonephritis

Renal glomerular disease characterized by the deposition of immunoglobulin light chains or monoclonal immunoglobulins was demonstrated by immunofluorescence microscopy in 11 patients. The most common histopathologic findings were those of mesangiocapillary glomerulonephritis, but considerable variability was observed. Lesions resembling diabetic glomerulosclerosis and amyloidosis were seen in some patients. Immunofluorescence findings in seven patients showed concomitant, equally intense staining for kappa light chain and immunoglobulin heavy chain (IgG or IgA), indicative of monoclonal immunoglobulin deposition. Specimens in the remaining cases stained predominantly for kappa light chain alone. In six cases the histologic and ultrastructural pattern was similar to that of type I mesangiocapillary glomerulonephritis. In three cases linear deposits were present, predominantly in subendothelial and inner glomerular basement membranes and, to a lesser degree, in mesangial locations, as in type II mesangiocapillary glomerulonephritis. In one of the latter cases dense deposits were intermixed with aggregates of amorphous fibrillar material indistinguishable from amyloid. In two cases involving IgA kappa chain deposition the histologic and ultrastructural appearance was that of mesangial glomerulonephritis. Considerable heterogeneity was found in the clinical features of the patient population. Specific clinical or serologic parameters for this disease could not be identified. Only one patient had an associated lymphoplasmacytic disorder. After follow-up periods ranging from six months to 17 years, all of the patients were alive, including four who had progressed to end-stage renal disease and required dialysis. Two of the latter patients underwent successful renal transplantation; one had been alive for five years and the other for three months without evidence of recurrence of the renal disease at the last follow-up examination.     

Glomerular alterations associated with obstructive jaundice

An immunohistochemical and clinicopathologic analysis of glomerular alterations was carried out in 20 autopsy cases with obstructive jaundice. The 20 cases without clinical nephritis had primary carcinoma of various locations, including the stomach, rectum, pancreas, and biliary tract. Mesangial IgA deposition was present on immunofluorescence staining in four cases, IgG in two cases, IgM in five cases, and C3 in four cases. Glomerular polymeric IgA containing A1, A2, and J chain was considered to originate from the gastrointestinal tract. All immunofluorescence-positive cases except one had electron-dense deposits in mesangial regions. These findings suggest that glomerular IgA deposition develops in a handful of patients suffering from obstructive jaundice, presumably due to the passive trapping of circulating immune complexes. Furthermore, glomerular IgA deposition in patients with obstructive jaundice is not influenced by duration or intensity of jaundice, and it unlikely induces clinical nephritis.     

Significance of mesangial IgA deposition in minimal change nephrotic syndrome: a study of 60 cases

We studied 60 cases of minimal change nephrotic syndrome (MCNS) with mesangial IgA deposits occurring over a 6 year period. There were 43 adults and 17 children. Hematuria occurred in 69.0% of the adults and 88.2% of the children. Two adults and six children had gross hematuria during the course of the disease. Mesangial IgA deposits were noted in 100% of the cases, and concomitant IgG or IgM deposits were found in 78.6% of adults and 73.7% of children. The fluorescent intensity of mesangial IgA deposits was trace (+/-) to 1+ in 86.1% and 70.6% of the adults and children respectively. Most of the patients showed electron microscopic findings consistent with minimal change nephrotic syndrome. We speculate that most of our cases are variants of minimal change nephrotic syndrome but are neither IgA nephropathy nor an overlapping syndrome, and that environmental or genetic factors may be related to the deposition of IgA in these MCNS patients.     

Mucin secreting cancer with mesangial IgA deposits

Subclinical immune complex glomerular deposits occurred in 20% (11 of 55) of cancer cases examined postmortem. Eight of 11 (72.7%) mucin secreting adenocarcinomas of lung, stomach, large intestine and pancreas showed glomerular mesangial deposits of IgA, with associated IgM and C3 in one-half of them. The glomerular morphology showed predominantly minimal or minor changes, and less frequently mesangial cell proliferation. None of the patients exhibited clinical evidence of glomerulonephritis. The nature of the antigen(s) in the paraneoplastic phenomenon was not defined, but there may have been environmental antigen(s) or specific immune response in the local population to explain the IgA deposition.     

Immunoglobulin and complement deposition in glomeruli of 756 subjects who had committed suicide or met with a violent death.

AIMS--To study immune deposits in renal glomeruli. METHODS--Tissue was obtained from 756 necropsy cases from people who had committed suicide or met with a violent death. Glomerular immune deposits were examined by immunofluorescence microscopy and a light microscopy. The clinical histories of all the decreased were studied to ascertain reasons for the deposits. RESULTS--Immune deposits were found in glomeruli in 91 (12%) cases. In 52 (6.8%) cases mesangial IgA was observed as a solitary finding in 34 (4.5%), and was accompanied by other immunoglobulins in 18 (2.4%). Mesangial IgM was present in 19 (2.5%) and IgG in 11 cases (1.5%). Two cases had capillary IgG (0.3%). Light microscopic examination showed mesangial enlargement in eight of the cases with mesangial IgA. These included one with IgA glomerulonephritis diagnosed before death. Two cases with normal glomerular morphology and mesangial IgA deposits had clinical laboratory evidence of renal disease. In two subjects with normal glomerular morphology, mesangial IgM and microscopic haematuria were present. In one case with capillary IgG membranous glomerulonephritis was detected. CONCLUSIONS--Ten cases had mesangial IgA together with morphological or clinical laboratory findings suggestive of renal disease. If all these are regarded as IgA glomerulonephritis, then its prevalence can be estimated at 1.3%. For IgM glomerulonephritis, a prevalence of 0.3% was deduced.     

Glomerular electron-dense deposits in childhood IgA nephropathy

Summary An electron-microscopic study of the glomeruli was made on 154 children with IgA nephropathy and no evidence of systemic disease, in whom immunofluorescence microscopy had shown diffuse mesangial deposition of IgA. Mesangial deposits were observed in all but eight children. Subepithelial deposits were observed in 40 children and were almost always accompanied by both mesangial and subendothelial deposits. Subepithelial deposits were significantly associated with more severe clinical presentations, a worse outcome and more severe light microscopic glomerular changes. These observations support the concept that IgA nephropathy is an immune complex disease.     

Immunoelectron microscopic studies of immune complex deposits and basement membrane components in IgA nephropathy

The relationship between the immune complex deposits of mesangial IgA nephropathy and the basement membrane components, type IV collagen and fibronectin, has been investigated by an indirect immunogold technique in four cases of mesangial IgA disease. Using paraformaldehyde-fixed, Lowicryl K4M resin-embedded kidney, IgA, IgM and C3 were localized in the mesangial electron-dense deposits with 10 and 20 nm gold-labelled secondary antibodies. In the same glomeruli, type IV collagen and fibronectin were rarely present within the electron-dense deposits, although both were distributed throughout the remainder of the mesangial matrix with the exception of the subepithelial regions. These two components were also present within the glomerular basement membrane and localized mainly on the endothelial aspect. A similar distribution of the basement membrane components was seen in a control kidney processed in the same way. This technique gives reproducible results and has demonstrated for the first time the relationship between the mesangial immune complex deposits of mesangial IgA nephropathy and the basement membrane components of the matrix in which they are found.     

Glomerular C4d deposition indicates in situ classic complement pathway activation,but is not a marker for lupus nephritis activity

This study was designed to evaluate whether glomerular C4d deposition may be a useful marker of lupus nephritis activity. Twenty-one patients diagnosed as having lupus nephritis (WHO class III: 4 cases; IV: 12 cases; V: 5 cases) were included. Mean patient age was 29.3 +/- 13.5 years (range: 7-55 years). The presence and intensity of glomerular C4d deposition were compared with the corresponding histologic activity index for each case. Immunofluorescence for C4d showed diffusely granular staining along glomerular capillary loops, in all cases examined (1+, in 8 cases; 2+, in 7 cases; 3+, in 6 cases). In eight cases, C4d deposition was found in the absence of capillary or mesangial C4 deposits. Moreover, the intensity of C4d deposits correlated with those of capillary IgG, IgA, C4, C1q, and fibrinogen deposits. However, C4d staining intensity did not correlate with the lupus nephritis activity index. Although glomerular capillary C4d deposition is a sensitive marker of classic complement pathway activation, it is not a sensitive marker for active lupus nephritis.     

Glomerular lesions associated with liver cirrhosis: an immunohistochemical and clinicopathologic analysis

Clinicopathologic and immunohistochemical analyses of the kidneys in 30 autopsy cases of liver cirrhosis of different types revealed glomerular lesions in 27 cases. Clinical nephritis was present in three cases. Characteristic diffuse mesangial proliferation with focal mesangial interposition and/or subendothelial deposits were present. Glomerular immunoglobulin deposition was observed in several cases, IgM in 23 cases, IgG in five, and IgA in 17; the latter were predominantly IgA1. Secretory component binding was found in 11 of the 17 cases with IgA deposits (65 per cent). Liver weight was related to IgA deposition (P approximately 0.05), and the volume of ascitic fluid was significantly correlated (P less than 0.05).     

Experimental cholestasis promotes the deposition of glomerular IgA immune complexes.

Previous experimental and clinical studies support a role for the hepatobiliary system in the clearance of oligomeric IgA from serum, and alterations of this system have been associated with the deposition of IgA in the renal mesangium. The present studies in mice address the question of whether the mesangial deposition of IgA following cholestasis includes immune complexes. While bile duct ligation resulted in mesangial IgA deposition within several days in approximately 75% of animals, whether deliberately orally immunized, nonimmunized, or given injected immune complexes, mice that underwent sham operations had IgA deposits only if orally immunized. Moreover, mice that had been orally immunized or given injected immune complexes and whose bile ducts had been ligated contained deposits of specific IgA antibody and antigen. In the ligated mice some of the IgA was secretory IgA, as demonstrated by the presence of secretory component. Thus, bile duct ligation promotes the deposition of circulating IgA immune complexes, presumably by decreasing their clearance from serum, and gives rise to secretory IgA in the glomerular mesangium. The secretory immune system probably plays a role in the pathogenesis of idiopathic and cirrhosis-related human IgA nephropathy.