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补体成分C4d免疫组化染色的系列研究Ⅲ

发布时间:2018-09-11 12:57
【摘要】: 【目的】 1.研究不同亚型的原发性局灶节段性肾小球硬化症(FSGS)中C4d与其它补体成分及免疫球蛋白沉积的形态特点及各观察指标之间的相互关系。进一步探讨补体与免疫球蛋白在FSGS发生发展过程中的作用。 2.观察FSGS早期C4d表达的特点,探讨C4d在FSGS早期诊断以及鉴别诊断中的价值。 3.观察供受体血型不合肝移植中C4d沉积的特点,探讨移植肝体液排异反应的诊断标准。 【方法】 1.选择我科经光镜、免疫组化和电镜检查确诊的肾病组织蜡块共计260例,其中诊断为FSGS的153例;早期FSGS 33例(顶端型9例,非特殊型11例,门部型13例);疑似FSGS 23例;肾小球轻微病变21例;微小病变性肾小球病30例,分别行HE、PAS、PASM染色和二步法免疫组化IgG、IgM、IgA、C3c、C4c、C4d、C1q和Fib等染色。另外选择20例因肿瘤(血管平滑肌脂肪瘤16例,肾透明细胞癌4例)行手术切除肾脏标本,取距肿瘤5cm以上且无病变肾组织,作为免疫组化C4d染色对照组。 2.对以上收集的标本进行电镜常规制片,铀铅双染色,在电镜下进行超微结构观察。 3.采用常规染色和免疫组化的方法,观察2例供受体血型不合肝移植的病理改变以及肝组织中各种免疫球蛋白和补体的沉积情况。 【结果】 1. FSGS中以IgM和C4d沉积为主,尤其C4d表达阳性率最高(90.8%),而且C4d沉积往往伴有C1q沉积。 2.线状沉积组C4d平均阳性积分显著高于非线状沉积组(P0.01),而且前者具有较高的激素抵抗发生率和高血压发生率。 3.本组细胞型和塌陷型C4d阳性率均为100%,二者C4d沉积阳性积分略高于其它各组。二者IgM沉积阳性率均高于非特殊型组,差异具有显著性(P0.01);塌陷型C1q阳性率为87.5%,高于其它各组,而且其平均阳性积分高于其它各组,并且具有显著性差异(P0.01)。同时塌陷型患者病程较短,高血压发生率较高,患者血白蛋白水平低,平均24h尿蛋白定量水平较高,肾功能不全的发生率较其它亚型患者高。 4.早期FSGS中可见C4d在肾小球局灶节段硬化处强阳性表达,包括基底膜线状沉积和系膜区颗粒状沉积。 5. 2例移植肝的肝血窦内皮细胞上有不同程度IgG、IgM、IgA、C4c、C4d和C1q线状或颗粒状沉积。 【结论】 1. FSGS硬化病变处存在C4d强阳性表达,提示补体经典途径强烈激活。FSGS中C4d沉积方式有两种:基底膜线状沉积和系膜区颗粒、团块状沉积。线状沉积代表经典补体途径更强激活,提示患者预后较差和对激素治疗不敏感。 2. C4d沉积强度和方式可作为判断FSGS治疗及预后的重要指标。 3.局灶节段线状颗粒状C4d强阳性表达是早期FSGS的一个重要免疫病理形态指标,对其诊断和鉴别诊断很有意义。C4d染色有助于FSGS早期诊断,基底膜上C4d线状沉积可以作为比球囊粘连更前期的FSGS形态表现。 4. IgG等免疫球蛋白在肝窦内皮细胞上弥漫强阳性沉积,并伴有C4d等补体成分表达,可作为移植肝组织中存在体液排异反应的证据。
[Abstract]:[Objective]
1. To study the morphological characteristics of C4d and other complement components and immunoglobulin deposits in different subtypes of primary focal segmental glomerulosclerosis (FSGS) and the relationship between the complement and immunoglobulin.
2. to observe the characteristics of C4d expression in early stage of FSGS, and to explore the value of C4d in early diagnosis and differential diagnosis of FSGS.
3. To observe the characteristics of C4d deposition in donor-recipient incompatible liver transplantation and to explore the diagnostic criteria of humoral rejection.
[method]
1. A total of 260 cases of nephrotic tissue wax masses were diagnosed by light microscopy, immunohistochemistry and electron microscopy, including 153 cases of FSGS, 33 cases of early FSGS (9 cases of apical type, 11 cases of non-special type, 13 cases of portal type), 23 cases of suspected FSGS, 21 cases of minor glomerular lesions, 30 cases of minimal glomerulopathy, HE, PAS, PASM staining and two-step staining, respectively. Methods Immunohistochemical staining of IgG, IgM, IgA, C3c, C4c, C4d, C1q and Fib was performed. In addition, 20 cases of renal tumor (16 cases of angiomyolipoma, 4 cases of clear cell carcinoma of kidney) were selected for surgical resection. The renal tissues above 5 cm away from the tumor without pathological changes were taken as immunohistochemical C4d staining control group.
2. The specimens collected above were routinely sliced under electron microscope, stained with uranium and lead, and observed under electron microscope.
3. The pathological changes of donor-recipient incompatible liver transplantation and the deposition of immunoglobulins and complements in liver tissues were observed by routine staining and immunohistochemistry.
[results]
1. In FSGS, IgM and C4d deposits were predominant, especially C4d deposits with the highest positive rate (90.8%).
2. The average positive score of C4d in linear deposit group was significantly higher than that in non-linear deposit group (P 0.01), and the former had higher incidence of hormone resistance and hypertension.
3. The positive rate of cell-type and collapse-type C4d was 100% in this group, and the positive integral of C4d deposition was slightly higher than that of other groups. The positive rate of IgM deposition was higher than that of non-special-type group, and the difference was significant (P 0.01); the positive rate of collapse-type C1q was 87.5%, higher than that of other groups, and the average positive integral of collapse-type C1q was higher than that of other groups. At the same time, patients with collapse type had shorter course of disease, higher incidence of hypertension, lower serum albumin level, higher urinary protein level in 24 hours on average, and higher incidence of renal insufficiency than other subtypes.
4. In early FSGS, C4d was strongly expressed in focal glomerular segmental sclerosis, including basement membrane linear deposition and mesangial granular deposition.
There were linear or granular deposits of IgG, IgM, IgA, C4c, C4d and C1q in the sinusoidal endothelial cells of transplanted liver in 2 cases.
[Conclusion]
1. Strong C4d positive expression in the sclerotic lesions of FSGS suggests that the classical complement pathway is strongly activated. There are two types of C4d deposition in FSGS: linear deposition in basement membrane and granular deposition in mesangial area, mass deposition. Linear deposition represents the stronger activation of classical complement pathway, suggesting poor prognosis and insensitivity to hormone therapy.
2. the intensity and manner of C4d deposition can be used as an important indicator for FSGS treatment and prognosis.
3. The strong positive expression of C4d in focal segment is an important immunopathological marker of early FSGS, and it is of great significance for its diagnosis and differential diagnosis. C4d staining is helpful for early diagnosis of FSGS. C4d linear deposition on basement membrane can be used as a morphological manifestation of FSGS earlier than balloon adhesion.
4. IgG and other immunoglobulins diffuse strong positive deposition on sinusoidal endothelial cells, accompanied by C4d complement expression, can be used as evidence of humoral rejection in liver transplantation.
【学位授予单位】:福建医科大学
【学位级别】:硕士
【学位授予年份】:2008
【分类号】:R392.31

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