免疫球蛋白沉积类型在IgA肾病中的意义

３１例小儿ＩｇＡ肾病报道结果表明：免疫球蛋白沉积类型与临床表现及组织损伤程度有一定关系。单纯系膜区ＩｇＡ沉积，组织损伤程度轻，临床多表现为单纯性血尿，预后较好，ＩｇＡ合并ＩｇＧ及／ＩｇＭ沉积者，易合并补体的沉积，组织损伤程度重，临床表现以肾病综合征及血尿合并蛋白尿发生率高。免疫复合物不仅沉积在系膜区，也可沉积在内皮下，并有相应的基底膜损伤。     

口腔扁平苔藓等病变组织中免疫沉积物的检测

用免疫金银染色检测被临床和组织病理确诊的２８例口腔扁平苔蓟（ＯＬＰ）和２０例慢性盘状红斑狼疮（ＤＬＥ）口腔损害组织标本中ＩｇＧ、ＩｇＡ、ＩｇＭ、补体Ｃ３和纤维蛋白原（Ｆｇ）的沉积状态，研究结果显示：ＯＬＰ在基底膜区（ＢＭＺ）的主要沉积物为Ｆｇ，占９６％，而ＩｇＧ（１０％）、ＩｇＡ（３．５％）、ＩｇＭ（７％）、Ｃ３（７％）沉积极少；ＤＬＥ在ＢＭＺ为Ｆｇ（９５％）、ＩｇＧ（８５％）、ＩｇＡ（９０％）、ＩｇＭ（７５％）、Ｃ３（８５％），其中ＩｇＧ、ＩｇＡ、ｌｇＭ、Ｃ３的沉积率明显高于ＯＬＰ，具有高度显著性差异（Ｐ＜０．０１）。     

接种缓释霍乱微球疫苗的试验研究

把霍乱弧菌Ｉｎａｂａ５６９Ｂ株的外膜蛋白（ＯＭＰ）包入可生物降解的聚乳酸－聚乙二醇共聚体内，制备成缓释微球疫苗。对微球在动物体内的靶向分布研究，表明口服微球后主要分布在肝、脾和肠系膜淋巴结等部位。采用微球疫苗免疫ＢＡＬＢ／ｃ小鼠后，收集其唾液、血清和粪便，采用ＢＡ－ＥＬＩＳＡ法检测了ｓＩｇＡ和ＩｇＧ抗体滴度。在第６周，口服微球疫苗组的小鼠粪便ｓＩｇＡ滴度比口服游离ＯＭＰ对照组高５倍；在第１２周时ｓＩｇＡ高达１０倍（２２４／２２），同时小鼠血清ＩｇＧ滴度也比对照组高１４倍（１９２０／１４０）。采用霍乱弧菌经腹腔攻击免疫小鼠后，发现口服微球疫苗组保护率为５０％～７０％，皮下注射微球疫苗组保护率为８０％～１００％，而口服游离ＯＭＰ组保护率仅为１０％。     

蜂毒的免疫调节机制研究

目的：探讨蜂毒对免疫系统的调节作用。方法：对健康志愿者蜂毒螯剂,分别于螯刺前后检测血浆及单个核细胞（ＰＢＭＣ）经ＰＨＡ诱导产生的ＩＬ－２／ＩＬ－４,以及ＩｇＧ、、ＩｇＡ、ＩｇＭ、Ｃ３,反映机体细胞免疫及体液免疫功能变化。结果：蜂毒后机体血浆及诱导ＰＢＭＣ产生的ＩＬ－２含量明显增高,血浆ＩＬ－４含量明显降低,诱生ＰＢＭＣ产生的ＩＬ－４无明显变化,同时血浆中的ＩｇＧ、ＩｇＡ、ＩｇＭ、Ｃ３的量在蜂疗前后     

小儿急性感染性多发性神经炎免疫功能状况动态观察

本文报告放射免疫法测定小儿急性感染性多发性神经炎２２例血清免疫球蛋白动态变化结果及细胞免疫功能的变化。发现本病急性期ＩｇＧ、ＩｇＡ高于正常，ＩｇＭ低于正常。细胞免疫功能低于正常，（Ｐ＜０．０１）。恢复期ＩｇＧ、ＩｇＡ仍高于正常，细胞免疫功能虽有所恢复，但仍低于正常。（Ｐ＜０．０５）。急性期与恢复期相比，ＩｇＧ无变化，ＩｇＡ、ＩｇＭ比急性期升高。（Ｐ＜０．０５）。     

习惯性流产与几种自身抗体的关系

本文对３１６例不明原因的习惯性流产者，用酶联免疫分析进行抗心磷脂抗体（ＡＣＡ）、抗血小板抗体（ＰＡ）及抗脱氧核糖核酸抗体（抗ＤＮＡ）测定，并与正常人比较。结果流产组ＡＣＡ、ＰＡ、抗ＤＮＡ阳性率分别为２３．７％、１６．７％、１３．６％，均显著高于正常对照组（Ｐ分别为〈０．０１，〈０．０１，〈０．０５），其中以ＡＣＡ－ＩｇＧ、ＡＣＡ－ＩｇＭ、ＰＡ－ＩｇＧ、ＰＡ－ＩｇＭ及ｓｓ－ＤＮＡ为主，它们与习惯性流     

小儿支气管哮喘发作期体液免疫改变

本文对３３例支气管哮喘发作期患儿进行了免疫球蛋白Ｅ、Ｇ、Ａ、Ｍ以及ＩｇＧ亚类的测定，设健康儿童对照组进行比较，结果表明：哮喘组ＩｇＥ平均值为７４７．３１ＩＵ／ｍｌ，对照组平均值为１０１．３４ＩＵ／ｍｌ，即哮喘患儿ＩｇＥ值明显高于对照组（Ｐ＜０．００１）。哮喘组ＩｇＧ亚类Ｇ１、Ｇ４分别为３．５３±１．４９、０．３３±０．１２，而对照组分别为４．９２±０．８３、０．２８±０．０８，两组之间有显著性差异（Ｐ＜０．００１）、（Ｐ＜０．０５）。Ｇ２、Ｇ３与对照组之间差异不显著。哮喘组ＩｇＧ值明显低于正常组，ＩｇＡ、ＩｇＭ值属正常范围。结果提示，小儿支气管哮喘发作期的体液免疫功能是紊乱的。     

母乳免疫球蛋白含量及相关因素探讨

从城市和农村分别采集产后２４小时内、产后第４天、产后１个半月及产后６个月母乳标本共１８０份，测定其ＩｇＡ、ＩｇＧ、ＩｇＭ含量。发现母乳中ＩｇＡ、ＩｇＧ、ＩｇＭ含量均随时间推移而显著下降。特别是ＩｇＡ，其产后２４小时内较第４天含量即呈显著性下降（Ｐ＜０．０１）。另地区、年龄、婴儿性别均对初乳中ＩｇＡ含量有显著影响（Ｐ＜０．０５）。吸烟使初乳中ＩｇＡ、ＩｇＧ、ＩｇＭ含量均呈显著性下降（Ｐ＜０．０５）。     

黄芪治疗11例IgG亚类缺陷病的疗效观察及机理初探

研究ＡＭ研究治疗１１例ＩｇＧ亚类缺陷病患儿的疗效及机理，结果表明ＡＭ治疗使患儿缺陷的血清ＩｇＧ１、ＩｇＧ３水平升高，ＰＢＭＣ体外产生ＴＦＮ－γ水平升高。治疗半年后呼吸道感染频率及患病时间明显降低，提示ＡＭ部分改善ＩｇＧ亚类缺陷患儿免疫功能，减少呼吸道感染发生。     

血清抗心磷脂抗体与冠心病相关性研究

为了解血清ＡＣＡ水平恙冠心病相关性，分别用ＥＬＩＳＡ和免疫比浊法对１４８名健康中老年人的ＡＣＡ－ＩｇＧ、ＩｇＭ、ＩｇＡ和ＴＣ、ＨＤＬ含量进行了检测，同时测定了３４例住院冠心病人的ＡＣＡ水平。结果表明：在正常组，３类ＡＣＡ均随年龄递增（Ｐ〈０．０１和Ｐ〈０．０５），且男性高于女性（Ｐ〈０．０１和Ｐ〈０．０５），其中ＡＣＡ－ＩｇＧ的消长与血清ＴＧ呈正相关（Ｐ〈０．０５）；冠心病组的ＡＣＡ－ＩｇＧ阳性检     

Significance of broad distribution of electron-dense deposits in patients with IgA nephropathy

Immunoglobulin A nephropathy (IgAN) is characterized by mesangial cell proliferation and mesangial expansion with mesangial depositions of IgA. We have found that electron-dense deposits (EDD) are often observed in areas other than paramesangial areas in glomeruli. To compare electron microscopic findings with light microscopic findings and clinical data, we examined the biopsies from 178 patients with IgAN. Patients were divided into two groups: group A had only paramesangial deposits and group B had deposits not only in paramesangial areas but also in other areas. All patients examined in this study had EDD in glomerular paramesangial areas. Thirty-six patients were included in group B. Cellular crescent formation in glomeruli and urinary protein in group B were significantly higher than those in group A (P < 0.01). Serum albumin and estimated glomerular filtration rate (eGFR) in group B were significantly lower than those in group A (P < 0.05). Group B showed a significant positive correlation with histological severity, which is defined in the Japanese Clinical Guidelines on IgAN. In patients with broad distribution of EDD, urinary protein was significantly increased (P < 0.05). Detailed observation of EDD distribution has an impact on evaluation of the disease activity of IgAN.     

肾小球疾病间质泡沫细胞的分布及其临床病理意义

目的 观测肾间质泡沫细胞浸润常见的肾小球疾病临床类型与病理类型以及各种病理类型肾小球疾病间质泡沫细胞的分布特点及其与病理参数间的关系.方法 选取行肾活检的2 862患者为研究对象,观察间质泡沫细胞浸润常见的病理类型及泡沫细胞的分布特点.对诊断明确的Aplort综合征(Aplort syndrome,AS)5例、膜增生性肾小球肾炎(membranous proliferative glomerulonephritis,MPGN)28例、局灶节段硬化性肾小球肾炎(focal segmental glomerulosclerosis,FSGS) 144例、特发性膜性肾病(idiopathic membranous nephropathy,IMN) 132例和IgA肾病(Iga nephropathy,IgAN) 893例按间质是否存在泡沫细胞进行病理参数的比较.结果 (1)肾间质泡沫细胞浸润常见于AS患者;原发性肾小球疾病泡沫细胞浸润高发的病理类型依次为MPGN(46.43%)、FSGS(20.14%)、IMN(13.64%)、IgAN(6.27%).(2)间质泡沫细胞浸润组节段硬化发生率及比例显著高于无泡沫细胞组(P<0.05),其间质纤维化程度亦显著高于无泡沫细胞组(P<0.05).结论 肾间质泡沫细胞浸润常见于AS,但在MPGN、FSGS、IMN和IgAN患者中均可出现.肾间质泡沫细胞的浸润与间质纤维化、肾小球硬化有一定的关联.间质泡沫细胞的出现可能与肾组织慢性化病变形成有关.     

用PCR-SSO检测IgA肾炎HLA-DRB1、DQA1、DQB1等位基因及其临床意义

利用聚合酶链区应（PCR）和序列特异性寡核苷酸（SSO）探针技术对47例经临床及免疫荧光证实的IgA肾病（IgAN）患者HLA-DRB1、DQA1、DQB1等位基因频率进行了检测。结果显示IgAN患者组DR4基因频率明显高于正常人组,相反DQB1*0602基因频率与对照组相比呈显著下降。IgAN患者中蛋白尿组DR4基因频率显著高于对照组,而肉眼血尿组与对照组无显著差异。约 1/4 DR4基因阳性的IgAN病理表现为局灶节段硬化性肾小球肾炎。 IgAN肾衰组DR4阳性的发生率显著高于非肾衰组。由此可见,IgAN中HLA-DR4基因频率而著增高, DR4阳性IgAN临床多表现蛋白尿,易发生肾衰,病理多呈局灶节段硬化型;DQB1*0602等位基因对IgAN可能有一定抵抗性。这些研究结果提示IgAN有免疫遗传的背景。     

Immunopathogenesis of IgAN

The defining hallmark of IgA nephropathy (IgAN) is deposition of polymeric IgA1 in the glomerular mesangium accompanied by a mesangial proliferative glomerulonephritis. The mechanisms involved in mesangial polymeric IgA1 deposition and the initiation of inflammatory glomerular injury remain unclear. This lack of a complete understanding of the pathogenesis of IgAN has meant that there is still no treatment known to modify mesangial deposition of IgA. Increasing evidence, however, supports the importance of IgA-containing immune complex formation as a pivotal factor driving mesangial IgA deposition and triggering of glomerular injury. A number of potentially important changes to the IgA1 molecule have been identified in IgAN, which may contribute to immune complex formation. These changes suggest that the polymeric IgA1 that deposits in IgA nephropathy is derived from mucosally primed plasma cells. The presence of this IgA in the circulation reflects displacement of mucosal B lineage cells to systemic sites and may be the result of mishoming of lymphocytes trafficking along the mucosa–bone marrow axis.     

Haemophilus parainfluenzae and IgA nephropathy]

IgA nephropathy (IgAN) was first reported by Berger in 1968, and characterized by diffuse IgA deposition in the mesangium. Patients with IgAN have usually episodic macroscopic hematuria accompanied with pharyngitis, gastroenteritis, bronchitis, or sinusitis. These findings suggest that IgAN is an immune-complex disease resulting from a poorly controlled mucosal immune response to environmental antigens to which the patient was chronically exposed. We reported the glomerular deposition of the outer membrane of Haemophilus parainfluenzae (OMHP) antigens and the presence of IgA antibody against OMHP in the sera of patients with IgAN. These suggest that Haemophilus parainfluenzae plays a role in the aetiology of this disease. This study was conducted to determine whether OMHP antigens induced immunohistologically evident glomerular deposition of IgA and C3 in C3H/HeN mice. Female C3H/HeN mice (4 weeks old) received intraperitoneal injection (HP-IP group), and oral administration (HP-PO group) of OMHP antigens. The control group similarly received intraperitoneal injection of PBS, and oral intake of ordinary water. The mice were sacrificed at 10, 20, 30, 40, 50 weeks after the start of the experiment. The HP-IP group showed glomerular deposition of IgA, C3 and OMHP antigens, glomerular changes (Mesangial hypercellularity and increase in mesangial matrix) after 20 weeks. The HP-PO group showed only mild deposition of IgA, and mild increase in mesangial matrix. These results suggest that OMHP antigens play a role in the glomerular deposition of IgA and C3 in C3H/HeN mice. This is the first use of OMHP antigens to establish an active model of IgAN.     

Development of immunoglobulin A nephropathy- like disease in beta-1,4-galactosyltransferase-I-deficient mice

Beta4 galactosylation of glycoproteins plays important roles in protein conformation, stability, transport, and clearance from the circulation. Recent studies have revealed that aberrant glycosylation causes various human diseases. Here we report that mice lacking beta-1,4-galactosyltransferase (beta4GalT)-I, which transfers galactose to the terminal N-acetylglucosamine of N- and O-linked glycans in a beta-1,4 linkage, spontaneously developed human immunoglobulin A nephropathy (IgAN)-like glomerular lesions with IgA deposition and expanded mesangial matrix. beta4GalT-I-deficient mice also showed high serum IgA levels with increased polymeric forms as in human IgAN. IgAN is the most common form of glomerulonephritis, and a significant proportion of patients progress to renal failure. However, pathological molecular mechanisms of IgAN are poorly understood. In humans, abnormal character of serum IgA, especially serum IgA1 with aberrant galactosylation and sialylation of O-glycans in its hinge region is thought to contribute to the pathogenesis of IgAN. Mouse IgA has N-glycans but not O-glycans, and beta4-galactosylation and sialylation of the N-glycans on the serum IgA from beta4GalT-I-deficient mice was completely absent. This is the first report demonstrating that genetic remodeling of protein glycosylation causes IgAN. We propose that carbohydrates of serum IgA are involved in the development of IgAN, whether the carbohydrates are O-glycans or N-glycans.     

IgA肾病患者临床与病理分析

目的探讨IgA肾病患者的临床表现和肾脏病理的特点及其相互关系。方法收集62例IgA肾病患者的临床资料及肾脏病理资料并进行统计学分析。结果病理类型中以系膜增生性、局灶节段增生性、局灶节段性硬化症三种最多，共占90．32％。Lee氏病理分级中以Ⅲ、Ⅳ级最多，共82．26％，随着Lee氏病理分级程度的增高。血压、血肌酐、血尿酸、24h尿蛋白量有不同程度的升高趋势（P〈0．05或P〈0．01）。Katafuchi积分与收缩压、血肌酐、血尿素氮、血尿酸、24h尿蛋白量呈显著正相关（P〈0．01）。结论IgA肾病肾脏病变与血压、肾功能、24h尿蛋白量等临床表现之间存在明显的相关关系。     

甘露糖结合蛋白基因多态性在IgA肾病肾组织免疫沉积多样性形成中的作用

目的 探讨甘露糖结合蛋白（mannose-binding protein,MBP)基因第54号密码子GGC→GAC变异在IgA肾病（IgA nephropathy,IgAN)患者肾小球免疫沉积多样性形成中的作用。方法 选取140名正常健康成人,147例IgAN患者,其中77例为单纯IgA伴C3沉积（A组）,70例为IgA,IgG,IgM伴C3、C1q沉积（AGM组）。使用PCR－RFLP法分析MBP基因型;同时应用ELISA法对58例IgAN患者和32名正常人血清MBP浓度进行了测定,分析比较MBP不同基因型与其血清浓度之间的关系。结果 （1）MBP基因GAC型等位基因与IgAN的大量免疫沉积明显相关（OR＝1.95,95%CI:1.06-3.58).（2）无论在A组还是在AGM组,GAC等位基因携带者中起病时有前驱感染史者均显著多于GGC合子（P＜0．05）。（3）不同人群中,GGC／GGC型血清MBP水平均明显高于GGC／GAC型（P＜0．0001）,GAC／GAC型血清MBP水平接近于0。结论 IgAN患者肾小球免疫沉积物的类型与MBP基因多态性密切相关。不同个体先天性防御屏障功能的差异在IgAN肾小球免疫沉积多样性的形成中发挥了重要作用。     

Clinicopathologic comparisons of IgA nephropathy and IgA vasculitis nephropathy in children: a ten-year single-center experience

Background/aim To investigate the similarities and differences of renal clinical and renal pathology between IgA nephropathy (IgAN) and IgA vasculitis nephritis (IgAVN) in children. Materials and methodsA total of 237 children with IgAN and 190 children with IgAVN were included. The general conditions, clinical characteristics, final diagnosis, clinical and pathological classification of the children were intercepted at the time of admission, and the retrospective comparative analysis was carried out. ResultsThe results showed that the median course of disease in IgAN group was longer than that in IgAVN group (p = 0.02). Patients with IgAN had a significantly higher duration of infection than the patients with IgAVN (p = 0.03). The white blood cell count (WBC), hemoglobin (HGB) in IgAN group were significantly lower than that in IgAVN group (p = 0.02). The serum creatinine in IgAN group was higher than that in IgAVN group (p = 0.02). Patients with IgAN and IgAVN had statistically significant differences in pathological typing between clinical types: hematuria and proteinuria, nephrotic syndrome and chronic nephritis (p = 0.004). ConclusionThe clinical manifestations of IgAN and IgAVN were similar, but the onset of IgAN was hidden and the clinical manifestations were relatively serious. Renal pathology was mainly glomerulosclerosis and renal tubular atrophy. IgAVN was characterized by acute onset and good renal function. Renal pathology was dominated by endothelial hyperplasia and crescent formation. These differences did not support the hypothesis that the two diseases are the same.     

Defective immunoglobulin A (IgA) glycosylation and IgA deposits in patients with IgA nephropathy

Defective glycosylation and immune complex (IC) formation may be of primary importance in immunoglobulin A nephropathy (IgAN) pathogenesis. The aim of this study was to determine whether defective IgA1 glycosylation might support renal deposition of IgA and disease activity. IgA was isolated from the serum of 44 IgAN patients and 46 controls and glycosylation analysed by ELISA using glycan‐specific lectins. IgA was measured by immunodiffusion and immune complexes by ELISA. IgA subclasses in IC deposits in kidney glomeruli were identified by immunohistochemical methods. A significant increase in N‐acetylgalactosamine (GalNAc) in terminal position (p = 0.02) observed in some of the IgAN patients, became more pronounced when sialic acid was removed from IgA1, indicating enhanced expression of α‐2,6‐sialyltransferase in patients compared with controls (p < 0.0001). Patients with defective galactosylation had lower serum IgA than other IgAN patients (p = 0.003). IgAN patients with both IgA1 and IgA2 glomerular deposits (21.7%) had increased GalNAc in terminal position (p = 0.003). Taken together, our results show that increased IgA glycosylation in IgAN associates with low levels of IgA, concomitant IgA1 and IgA2 glomerular deposits and poor clinical outcome.