血清cystatin C,IgA/C3及IgA/C3检测在IgA肾病诊断及预后评估中的临床价值

目的 探讨IgA肾病患者血清cystatin C,IgA和IgA/C3比值在IgA肾病(IgAN)的诊断及预后中的临床价值.方法 应用乳胶增强散射比浊法测定62例IgAN患者和58例非IgAN患者血清cystatin C,IgA及C3含量,同时对检测结果进行分析.结果 ①IgAN患者血清cystatin C水平[(1.26±0.46)mg/L] 与非IgAN患者血清cystatin C[(1.66±1.17)mg/L] 水平比较,差异有统计学意义(t=-2.50,P<0.05);IgAN患者血清IgA/C3比值(2.59±1.41)显著高于非IgAN患者(2.07±1.03),差异亦有统计学意义(t=2.33,P<0.05);而血清IgA含量[(2.44±1.04)g/L]和C3 含量[(1.07±0.27)g/L] 与非IgAN患者比较差异均无统计学显著性意义;② Lee氏分级为Ⅲ,Ⅳ,V级的IgAN患者血清IgA水平及IgA/C3比值均显著高于Lee氏I和Ⅱ级,差异有统计学意义(t=-2.21,P<0.05;t=-2.04,P<0.05);③IgAN患者IgA水平>3.0 g/L和IgA/C3比值≥2时诊断IgAN的敏感度、特异度、阳性预测值、阴性预测值及Youden指数YI分别为68.42%,51.48%,20.97%,89.66%,0.20和59.68%,56.90%,59.68%,56.90%,0.17.结论 血清IgA/C3比值联合IgA及cystatin C水平可作为IgAN鉴别诊断、病情判断、预后评估的参考指标;血清cystatin C可能是反映IgA肾病中肾小球滤过功能更为敏感的指标.     

血清异常IgA测定诊断IgA肾病的新方法

目的将糖生物学理论与免疫技术相结合,建立一种血清学检测诊断IgA肾病(IgAN)的新方法,以解决只能依靠肾活检穿刺术诊断IgAN问题.方法应用特异性识别糖链末端的凝集素,并结合抗人IgA特异抗体的酶联免疫吸附法(ELISA),检测血清中糖链异常的IgA的水平.结果采用该方法,对各组血清405nm吸光值测定结果表明正常对照组测定值0.22±0.10(n=156),IgAN确诊病人组0.68±0.17(n=22),两者差异有显著意义(P<0.001);IgAN疑诊病人组的测定值0.38±0.15(n=19),高于正常对照组.22份确诊的IgAN病人血清中,与病理诊断的阳性符合率为81.8%(19/22),而假阳性率仅为1.9%(3/156).结论血清中糖链异常IgA分子的凝集素亲和-ELISA检测方法,具有灵敏度高、特异性好的优点,对于IgAN的诊断具有一定的临床应用价值.     

血清IgA、IgA/C3比值在IgA肾病的诊断价值

目的探讨体检发现的IgA肾病(IgAN)患者血清IgA、IgA/C3比值在病理损伤评估和诊断预测方面的价值。方法 2005年8月至2010年12月因体检异常来中山医院就诊并经肾活检确诊为IgAN患者239例,回顾性分析这些患者的临床病理资料。所有患者都检测血清IgA、C3水平,病理学分级参照Lee′s分级标准。结果 IgAN患者血清IgA、IgA/C3水平较其他非IgA肾脏病理类型患者高;IgA、IgA/C3与IgAN病理损伤程度无相关性(P>0.05),二者的ROC曲线下面积分别为0.597、0.611。结论血清IgA、IgA/C3比值在IgAN患者明显升高,但二者水平与病理病变无相关性,对体检发现的IgAN诊断预测价值较低。     

IgA肾病患者血清IgA及治疗前后尿液IL-6水平改变的临床价值

目的 探讨IgA肾病(IgA nephropathy,IgAN)患者血清IgA和尿液白细胞介素-6(urinary interleukin-6,uIL-6)水平的应用价值及疗效判断中的临床意义.方法 应用乳胶增强散射比浊技术及酶联免疫(ELISA)法测定63例IgAN患者和30例健康对照者血清IgA及尿液IL-6水平,同时对检测结果进行分析.结果 IgAN患者血清IgA为(2.23±0.87)g/L及uIL-6水平(29.05±2.63)ng/L明显高于健康对照组(1.43±0.50)g/L和(20.22±4.38)ng/L,差异有统计学非常显著性意义(P＜0.01);IgAN患者治疗前、后uIL-6水平差异显著(P＜0.05);尿液中白细胞增加和血尿伴蛋白尿的IgAN患者uIL-6水平与健康对照组相比差异非常显著(P＜0.01);IgAN患者治疗前、后uIL-6水平比较差异非常显著(P＜0.01);单纯性血尿的IgAN患者治疗后的uIL-6水平与健康对照组无显著性差异(P＞0.05).结论 IgAN患者血清IgA及uIL-6水平明显高于健康对照组,uIL-6检测可以作为IgAN肾小球损伤向慢性化进展的一项指标.IgAN患者治疗前后uIL-6水平的改变对疗效的观察及预后判断具有一定的临床价值.     

糖基化异常的IgA1分子与IgA肾病

IgA 肾病（IgA nephropathy,IgAN）是常见的原发性肾小球疾病之一,以反复发作的肉眼血尿或镜下血尿及蛋白尿为主要临床表现,部分患者可出现高血压或肾功能不全,它是导致肾功能衰竭的主要原因之一。IgAN 为一种自身免疫性疾病,涉及感染、遗传、自身免疫等多种因素,其准确的致病机制却仍不清楚。本文对 IgAN 的发病特点、IgA1的分子结构、IgA1的异常糖基化及其致病方式等作一综述。     

原发性IgA肾病伴新月体形成的研究进展

IgA肾病(IgA nephropathy,IgAN)是全世界范围内最常见的原发性肾小球肾炎,以异常IgA1在肾小球系膜区沉积为主要特征.其临床和病理特征表现多样,新月体形成是IgAN的常见病理改变之一.IgAN合并新月体对疾病进展及预后的影响在不同种族、人群患者中的研究结论并不一致.本文综述了原发性IgAN患者伴新月...     

IgA肾病中医研究进展

正IgA肾病(IgAN)是以肾小球系膜区IgA为主的免疫球蛋白和补体沉积为特征的免疫复合物肾小球肾炎。临床特点以肉眼或镜下血尿为主,可伴有蛋白尿,甚至出现肾病综合征。本病是临床最常见的原发性肾小球疾病,约占原发性肾小球疾病的40%左右,在IgAN确诊后5~25年内有20%~40%患者可发展为慢性肾功能衰竭~([1])。近年来中、西医对本病的认识和治疗,都有很大的进展,西医目前对其仍无有效治疗方法,而通过相关临床观察和动物实验研究,证实     

IgA肾病的治疗进展

原发性IgA肾病(IgA nephropathy,IgAN)是一种免疫复合物介导的肾小球肾炎,以肾小球系膜IgA沉积为主要特征.IgAN是最常见的原发型肾小球疾病,它是各年龄段人终末期肾病的重要病因.     

性别与原发性IgA肾病临床及病理特点关系研究

正IgA肾病(IgAN)是导致终末期肾脏病的常见原发性肾小球疾病之一,其病理特点是肾小球系膜区以免疫球蛋白IgA沉积为主~([1,2])。IgAN临床表现多样,如血尿、蛋白尿、高血压等,以上临床表现与IgAN预后密切相关~([3])。在临床工作中发现原发性IgAN患者临床表现、病理特点与性别差异具有相关性,但是此观点仍存在一定的争议~([4])。本研究回顾232例原发性IgAN患者的相关资料,旨在探索     

IgA肾病预后相关因素的研究新进展

正IgA肾病(immunoglobulin A nephropathy,IgAN)是指肾小球系膜区以IgA或IgA沉积为主的原发性肾小球疾病,是肾小球源性血尿最常见的病因,是目前世界上最常见的原发性肾小球疾病,其发病率高。在世界范围内,IgAN占原发性肾小球疾病的30%～35%;在欧洲地区,占30%～40%;在亚洲地区,该比率高达45%;该病占我     

IgA nephropathy

Summary Seventy-five biopsy samples from patients with chronic renal disorders were examined by the usual techniques of light microscopy and immunofluorescence; in fifteen patients IgA nephropathy was found. These patients were young adults; the onset of the disease was characterized by macrohematuria, and recurrent episodes of hematuria were observed. Histological examination revealed proliferative endothelio-mesangial glomerulonephritis at various stages of development with focal or diffuse patterns; immunofluorescence revealed constant and intense positive reactions for IgA mainly in association with C3. It is assumed that there is a relationship connecting the more advanced histological changes, a more severe clinical course and the presence of IgM deposits.     

Increases of IgA milk concentrations correlate with IgA2 increment

IgA, IgA1, and IgA2 concentrations were determined in 81 defatted human milk samples: colostrum (days 1-5, n = 42), transitional milk (days 6-14, n = 18) and mature milk (days 15-75, n = 21) by immunonephelometry. Correlations were found between total IgA levels and the concentrations of both IgA subclasses (P < 0.0001). The levels of the three molecules decreased over lactation with significant differences (P < 0.05) between colostrum and transitional milk levels and between colostrum and mature milk. Colostral IgA1 and IgA2 mean concentrations dropped respectively from 10.89 +/- 2.12 g/L, and 15.41 +/- 2.10 g/L to 1.83 +/- 0.73 g/L and 3.40 +/- 1.25 g/L in transitional milk reaching finally to 0.36 +/- 0.07 g/L and 0.27 +/- 0.06 g/L in mature milk. IgA2 concentrations were higher than those of IgA1 when the total IgA level was high. The IgA2 levels in colostrum could be an adaptation resistance of IgA to potentially harmful pathogens able to secrete IgA proteases and also a way to regulate colonization of the microflora in the newborn.     

Differential susceptibility of human IgA immunoglobulins to streptococcal IgA protease

IgA protease, a proteolytic enzyme found in human saliva and colonic fluid, hydrolyzes human serum IgA immunoglobulins to yield Fab(alpha) and Fc(alpha) fragments. The enzyme is produced by organisms in the normal human microflora and can be purified from culture filtrates of the common human oral organism Streptococcus sanguis (American Type Culture Collection no. 10556). IgA protease is inactive against all other protein substrates examined including the other classes of human immunoglobulins. The role of this enzyme in affecting the function of the secretory IgA immune system is unknown.To further characterize and explain this unusual substrate specificity, the susceptibility of 31 human IgA myeloma proteins of both subclasses was investigated. 16 IgA1 and 15 IgA2 myeloma paraproteins were treated with enzyme and the extent of proteolysis was determined by cellulose actate electrophoresis, immunoelectrophoresis, polyacrylamide gel electrophoresis, and column chromatography. All IgA1 proteins were enzymatically cleaved to Fab(alpha) and Fc(alpha) fragments, but all IgA2 proteins were resistant, yielding no fragments after prolonged enzymatic treatment. N-terminal amino acid sequence analysis of the purified Fc(alpha) fragment of a single IgA1 paraprotein was as follows: Thr-Pro-Ser-Pro-?-Thr-Pro-Pro-Thr-Pro-Ser-Pro-Ser. Comparison of this sequence to that reported for the IgA1 heavy chain shows that the enzyme-susceptible peptide bond is a Pro-Thr in the IgA1 hinge region. The most likely explanation of the resistance of the IgA2 subclass to IgA protease is a deletion in the heavy chain which commences with the critical threonine of the susceptible Pro-Thr bond.     

Impairment of jacalin binding to serum IgA in IgA nephropathy

A test was set up to analyze the direct binding of serum IgA to the lectin jacalin. Under the testing conditions, jacalin bound to both IgA subclasses and reacted similarly with monomeric and polymeric IgA. A jacalin index was defined to quantify serum IgA binding to this lectin. The jacalin index appeared significantly lower in IgA nephropathy than in controls. This may be related to abnormal IgA glycosylation, which could explain, at least in part, the mesangial deposition responsible for the renal disease.     

IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1

Aberrant glycosylation of IgA1 plays an essential role in the pathogenesis of IgA nephropathy. This abnormality is manifested by a deficiency of galactose in the hinge-region O-linked glycans of IgA1. Biosynthesis of these glycans occurs in a stepwise fashion beginning with the addition of N-acetylgalactosamine by the enzyme N-acetylgalactosaminyltransferase 2 and continuing with the addition of either galactose by beta1,3-galactosyltransferase or a terminal sialic acid by a N-acetylgalactosamine-specific alpha2,6-sialyltransferase. To identify the molecular basis for the aberrant IgA glycosylation, we established EBV-immortalized IgA1-producing cells from peripheral blood cells of patients with IgA nephropathy. The secreted IgA1 was mostly polymeric and had galactose-deficient O-linked glycans, characterized by a terminal or sialylated N-acetylgalactosamine. As controls, we showed that EBV-immortalized cells from patients with lupus nephritis and healthy individuals did not produce IgA with the defective galactosylation pattern. Analysis of the biosynthetic pathways in cloned EBV-immortalized cells from patients with IgA nephropathy indicated a decrease in beta1,3-galactosyltransferase activity and an increase in N-acetylgalactosamine-specific alpha2,6-sialyltransferase activity. Also, expression of beta1,3-galactosyltransferase was significantly lower, and that of N-acetylgalactosamine-specific alpha2,6-sialyltransferase was significantly higher than the expression of these genes in the control cells. Thus, our data suggest that premature sialylation likely contributes to the aberrant IgA1 glycosylation in IgA nephropathy and may represent a new therapeutic target.     

Significance of serum IgA levels and serum IgA/C3 ratio in diagnostic analysis of patients with IgA nephropathy

Diagnostic analysis of clinical markers including serum IgA levels and serum IgA/C3 ratio in patients with IgA nephropathy is described. One hundred patients with IgA nephropathy (IgA nephropathy group) and 100 patients with other primary glomerular diseases (non-IgA nephropathy group) were examined. The analysis was performed to distinguish between these two groups using four clinical markers: 1) more than five red blood cells in urinary sediments, 2) persistent proteinuria (urinary protein of more than 0.3 g/day), 3) serum IgA levels of more than 315 mg/dl, and 4) a serum IgA/C3 ratio of more than 3.01. Patients with three or four clinical markers were easily diagnosed as having IgA nephropathy in this study. Furthermore, there was a significant difference in these clinical markers between the good prognosis and relatively good prognosis groups (Groups I and II) and the relatively poor prognosis and poor prognosis groups (Groups III and IV) of IgA nephropathy patients. It appears that the presence of microscopic hematuria and/or persistent proteinuria, high serum IgA levels, and the serum IgA/C3 ratio are useful for distinguishing IgA nephropathy from other primary renal diseases. It is postulated that these clinical markers are also useful for diagnosis of IgA nephropathy without renal biopsy.