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補體成分C4d免疫組化染色的系列研究Ⅲ

發(fā)布時間:2018-09-11 12:57
【摘要】: 【目的】 1.研究不同亞型的原發(fā)性局灶節(jié)段性腎小球硬化癥(FSGS)中C4d與其它補體成分及免疫球蛋白沉積的形態(tài)特點及各觀察指標之間的相互關(guān)系。進一步探討補體與免疫球蛋白在FSGS發(fā)生發(fā)展過程中的作用。 2.觀察FSGS早期C4d表達的特點,探討C4d在FSGS早期診斷以及鑒別診斷中的價值。 3.觀察供受體血型不合肝移植中C4d沉積的特點,探討移植肝體液排異反應(yīng)的診斷標準。 【方法】 1.選擇我科經(jīng)光鏡、免疫組化和電鏡檢查確診的腎病組織蠟塊共計260例,其中診斷為FSGS的153例;早期FSGS 33例(頂端型9例,非特殊型11例,門部型13例);疑似FSGS 23例;腎小球輕微病變21例;微小病變性腎小球病30例,分別行HE、PAS、PASM染色和二步法免疫組化IgG、IgM、IgA、C3c、C4c、C4d、C1q和Fib等染色。另外選擇20例因腫瘤(血管平滑肌脂肪瘤16例,腎透明細胞癌4例)行手術(shù)切除腎臟標本,取距腫瘤5cm以上且無病變腎組織,作為免疫組化C4d染色對照組。 2.對以上收集的標本進行電鏡常規(guī)制片,鈾鉛雙染色,在電鏡下進行超微結(jié)構(gòu)觀察。 3.采用常規(guī)染色和免疫組化的方法,觀察2例供受體血型不合肝移植的病理改變以及肝組織中各種免疫球蛋白和補體的沉積情況。 【結(jié)果】 1. FSGS中以IgM和C4d沉積為主,尤其C4d表達陽性率最高(90.8%),而且C4d沉積往往伴有C1q沉積。 2.線狀沉積組C4d平均陽性積分顯著高于非線狀沉積組(P0.01),而且前者具有較高的激素抵抗發(fā)生率和高血壓發(fā)生率。 3.本組細胞型和塌陷型C4d陽性率均為100%,二者C4d沉積陽性積分略高于其它各組。二者IgM沉積陽性率均高于非特殊型組,差異具有顯著性(P0.01);塌陷型C1q陽性率為87.5%,高于其它各組,而且其平均陽性積分高于其它各組,并且具有顯著性差異(P0.01)。同時塌陷型患者病程較短,高血壓發(fā)生率較高,患者血白蛋白水平低,平均24h尿蛋白定量水平較高,腎功能不全的發(fā)生率較其它亞型患者高。 4.早期FSGS中可見C4d在腎小球局灶節(jié)段硬化處強陽性表達,包括基底膜線狀沉積和系膜區(qū)顆粒狀沉積。 5. 2例移植肝的肝血竇內(nèi)皮細胞上有不同程度IgG、IgM、IgA、C4c、C4d和C1q線狀或顆粒狀沉積。 【結(jié)論】 1. FSGS硬化病變處存在C4d強陽性表達,提示補體經(jīng)典途徑強烈激活。FSGS中C4d沉積方式有兩種:基底膜線狀沉積和系膜區(qū)顆粒、團塊狀沉積。線狀沉積代表經(jīng)典補體途徑更強激活,提示患者預(yù)后較差和對激素治療不敏感。 2. C4d沉積強度和方式可作為判斷FSGS治療及預(yù)后的重要指標。 3.局灶節(jié)段線狀顆粒狀C4d強陽性表達是早期FSGS的一個重要免疫病理形態(tài)指標,對其診斷和鑒別診斷很有意義。C4d染色有助于FSGS早期診斷,基底膜上C4d線狀沉積可以作為比球囊粘連更前期的FSGS形態(tài)表現(xiàn)。 4. IgG等免疫球蛋白在肝竇內(nèi)皮細胞上彌漫強陽性沉積,并伴有C4d等補體成分表達,可作為移植肝組織中存在體液排異反應(yīng)的證據(jù)。
[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.
【學(xué)位授予單位】:福建醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2008
【分類號】:R392.31

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