环孢霉素A和地塞米松局部应用对角膜移植免疫排斥的疗效观察

报告１％环孢霉素Ａ（ＣｙｃｌｏｓｐｏｒｉｎＡ，ＣｓＡ）和地塞米松局部联合用药，治疗３１只眼穿透性角膜移植术后的免疫排斥反应，随访６～１８个月植片透明治愈为９３．５％，平均治愈时间７天，观察表明局部用药既能收到良好的疗效，又避免了全身用药的毒副作用，并对ＣｓＡ和地塞米松联合用药的机理及注意事项进行了讨论。     

Prevention of Acute Lung Allograft Rejection in Rat by CTLA4Ig

CTLA4 immunoglobulin (CTLA4Ig), which binds with a high affinity to B7-1 and B7-2, interrupts T-cell activation by inhibiting costimulatory signal. CTLA4Ig has been used in hopes of achieving antigen-specific tolerance induction in several solid organ transplants. In lung allograft rejection, however, its use has been controversial in terms of its effect on prevention of rejection. In the present study, the effect of murine CTLA4Ig on rat-lung allograft rejection was investigated. Rat left-lung transplantation was performed in an RT1 incompatible donor (Brown Norway; BN)-recipient (F344) combination. All allografts (n = 12) without any treatment were rejected within 7 days after transplantation. A single injection of murine form CTLA41g at a dose of 100 microg intraperitoneally (ip) or intravenously (iv) on day 1 post-transplantation achieved long-term graft survival (>90days) in 2/5 (40%) and 3/8 (38%), respectively. Moreover, 6/7 (86%) allografts in rats that received iv injection of 500 microg CTLA4Ig survived more than 90days. Allograft survival in the CTLA4Ig 500 microg iv recipient group was significantly longer than that in the no-treatment control or control immunoglobulin group (p <0.01). Four out of seven recipients bearing functional allografts for more than 90 days with the CTLA4Ig treatment accepted donor-specific skin grafts, whereas all third-party skin grafts (n=3) were rejected. Prevention of rat-lung allograft rejection could be achieved by intravenous administration of CTLA4Ig, resulting in long-term allograft survival with acceptance of donor-specific skin grafts.     

小剂量抗CD3单克隆抗体治疗肾移植术后早期急性排斥反应的临床研究

目的探讨应用小剂量抗CD3单克隆抗体(OKT3)治疗肾移植术后早期急性排斥反应的效果和安全性.方法将33例发生早期急性排斥反应的肾移植病人分为两组,A组16例(OKT3 5 mg/d);B组17例(OKT3 2.5mg/d).观察排斥反应逆转情况及感染的发生率.结果A组13例(81.25%)急性排斥反应逆转,移植肾功能恢复正常;1例移植肾自发性破裂行移植肾摘除术,2例移植肾失功恢复血液透析.B组15例(88.24%)急性排斥反应逆转,移植肾功能恢复正常;1例移植肾自发性破裂行移植肾摘除术,1例移植肾失功恢复血液透析.两组排斥反应逆转率无显著性差异(P＞0.05).A组合并感染43.75%,B组5.88%;两组比较有显著性差异(P＜0.05).结论小剂量OKT3治疗肾移植术后早期急性排斥反应的效果良好,并发症少,且费用较低.     

大剂量甲基强的松龙冲击治疗角膜移植术后排斥反应的临床疗效观察

目的观察大剂量甲基强的松龙冲击治疗角膜移植术后排斥反应的临床疗效。方法选择角膜移植术后排斥反应病例9例(9只眼),采用大剂量甲基强的松龙500mg冲击治疗1d,而后予以维持量糖皮质激素方法治疗,并随访观察1年。结果7例治愈,随访1年中角膜植片均保持透明;2例好转,随访1年中移植片基本透明,但仍有轻度水肿。结论大剂量甲基强的松龙冲击治疗角膜移植术后排斥反应疗效满意。     

Chronic Kidney Isograft and Allograft Rejection

In this study antigen-independent factor in the pathogenesis of chronic rejection of organ transplants was examined.Kidney isografts and allografts were transplanted orthotopically into bilaterally nephroectomized rat recipients and studied functionaaly,morphologically and immunohistologically,at serial intervals up to 52 weeks after transplantation.Allograft recipients developed progressive proteinuria after 12 weeks,with gradual renal failure ultimately leading to death.At the same time,morphological changes,including progressive arteriosclerosis and glomerulosclerosis ,tubular atrophy and interstitial fibrosis,developed.Immunohistologically,macrophages infiltrated glomeruli during this period and cytokines became unregulated.Our results showed that antigen-independent functional and morphological changes occurred in long-tern kidney isografts and mimicked those appearing much earlier in allografts that reject chronically.Initial injury and extent of functioning renal mass is suggested to be important factor for such late changes.     

Expression of cell-matrix molecules and integrin receptors in human liver grafts during chronic rejection

Abstract The inflammatory response of immune cells to target cells and cell-matrix molecules is regulated by several receptor-ligand molecules. As fibrosis develops in ongoing chronic rejection after liver transplantation, it is of interest to analyze patterns of integrin receptors and cell-matrix molecules in order to study the relation between immune cells and the stromal and parenchymal cells. In the present study, we demonstrated the expression of these molecules in chronic rejected human liver grafts using immunohistochemical techniques. The results showed a differential expression and induction of integrin receptors and cell-matrix molecules on resident liver cells, especially on sinusoids, reflecting a state of chronic inflammation and a specific interaction between integrin receptors and cell-matrix molecules. The patterns of induced integrin receptors on graft-infiltrating cells was closely related to the local production of cell-matrix molecules and reflected the final sequence of a stepwise progress of the inflammatory reaction.     

IL-2R 在急性细胞性排异反应的同种异体尸体移植肾组织中的检测及意义

为探讨白介素－２受体（ＩＬ－２Ｒ，即ＣＤ２５）在同种异体肾移植急性细胞性排异（ＡＣＲ）临床诊断的作用，着重观察移植肾发生（ＡＣＲ）和无ＡＣＲ时，其间质浸润细胞中ＩＬ－２Ｒ阳性细胞数的变化，及其与间质浸润的淋巴细胞的关系。作者选择同期行异体肾移植，且无并发症患者１７例，采用ＰＡＰ四层免疫酶标法，检测移植肾组织中间质浸润细胞中ＩＬ－２Ｒ阳性细胞数的变化。结果显示：无ＡＣＲ的肾组织中，ＩＬ－２Ｒ阳性细胞仅轻度增加，当移植肾出现ＡＣＲ时，ＩＬ－２Ｒ阳性细胞数的增加十分显著，并与间质浸润的ＣＤ８密切相关。作者认为ＩＬ－２Ｒ对于ＡＣＲ的诊断及鉴别诊断具有一定的临床应用价值。     

Human chronic kidney allograft rejection is accompanied by increased intraglomerular cathepsin B and L activity

Abstract The major reason for late graft losses is chronic rejection. Recently, a large number of studies have indicated that proteolytic enzymes play an important role as mediators of glomerular injury. The cysteine proteinases cathepsins B and L degrade structural matrix proteins such as type I collagen and laminin. We investigated intraglomerular protease activities in 12 patients after kidney graftectomy because of end-tage renal disease following chronic rejection. A group of 12 patients undergoing nephrectomy because of cancer served as controls using only non-involved parts of the kidney. The activities of cathepsins B and L in homogenates of isolated glomeruli were measured fluorometrically methylcoumarylamidc substrates and related to DNA content. In rejected kidney allografts we observed significantly enhanced intraglomerular cathepsin B activity and cathepsin B + L activity.     

尿流式细胞学在诊断移植肾急性排斥反应中的应用价值

目的：探讨尿流式细胞学在诊断移植肾急性排斥反应中的临床应用价值。方法：对43例肾移植受者的116份尿样本进行尿流式细胞学分析，并将急性排斥组和肾功能稳定组的分析结果进行比较。结果：急性排斥反应组尿淋巴细胞总数以及HLA－DR^ 淋巴细胞数显著增多，与肾功能稳定组比较，P＜0．01，CD8^ 细胞亦增多（P＜0．05），而CD3^ ,CD4^ ,CD19^ 细胞数变化两组差异不显著（P＞0．05），在诊断移植肾急性排斥反应上，HLA－DR阳性样本和淋巴细胞数阳性样本的诊断敏感性和特异性分别达95．2％，90．5％，和92．6％，87．4％，结论：尿流式细胞学分析可反映移植肾内的免疫状态，尿淋巴细胞数的显著增多和尿HLA－DR^ 淋巴细胞增多可以作为诊断急性排斥反应的有意义指标。     

Reduction in acute rejections decreases chronic rejection graft failure in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Chronic rejection accounted for 32% of all graft losses in 7123 pediatric transplants. In a previous study acute, multiple acute and late acute rejections were risk factors for the development of chronic rejection. We postulated that the recent decrease in acute rejections would translate into a lower risk for chronic rejection among patients with recent transplants. We reviewed our data on patients transplanted from 1995 to 2000, and using multivariate analysis and a proportional hazards model developed risk factors for patients whose grafts had failed due to chronic rejection. A late initial rejection increased the risk of chronic rejection graft failure 3.6-fold (p < 0.001), while a second rejection resulted in further increase of 4.2-fold (p < 0.001). Recipients who received less than 5 mg/kg of cyclosporine at 30 days post-transplant had a relative risk (RR) of 1.9 (p = 0.02). Patients transplanted from 1995 to 2000 had a significantly lower risk (RR = 0.54, p < 0.001) of graft failure from chronic rejection than those who received their transplants earlier (1987-94). Since we were able to demonstrate that there is a decreased risk of chronic rejection graft failure in our study cohort, we would conclude that the goal of future transplants should be to minimize acute rejections.