Roles of interleukin-10 in acute graft-versus-host disease and graft rejection

To study the role of interleukin(IL)-10 in acute-graft-versus-host disease (aGVHD) and graft rejection Methods Serum concentrations of IL-10 in 28 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) were measured by enzymed-linked immunosorbent assay (ELISA) IL-10 gene expression in peripheral mononuclear cells was measured by reverse-transcriptase polymerase chain reaction (RT-PCR) after transplantation Results Seven patients developed grade Ⅰ GVHD, 7 patients developed grade Ⅱ-Ⅳ GVHD, 4 patients had graft rejection Before transplantation, the concentrations of IL-10 were higher in patients who later did not developed aGVHD After transplantation, IL-10 levels increased in patients without aGVHD, but decreased in patients with aGVHD or graft rejection And IL-10mRNA was more frequent in patients without aGVHD compared to those with aGVHD Conclusions IL-10 plays a negative role in the development of aGVHD and graft rejection

Unsuccessful treatment of four patients with acute graft-vs-host disease after liver transplantation

AIM: To investigate appropriate therapeutic strategies for graft-vs-host disease (GVHD) following liver transplantation. METHODS: Four patients who developed GVHD after liver transplantation in West China Hospital were included in this study. Therapeutic strategies with augmentation or withdrawal of immunosuppressants combined with supportive therapy were investigated in these patients. In addition, a literature review of patients who developed GVHD after liver transplantation was performed. RESULTS: Although a transient response to initial treatment was detected, all four patients died of complications from GVHD: one from sepsis with multiple organ failure, one from gastrointestinal bleeding, and the other two from sepsis with gastrointestinal bleeding. Few consensuses for the treatment of GVHD after liver transplantation have been reached.CONCLUSION: New and effective treatments are re-quired for GVHD after liver transplantation to improve the prognosis of patients with this diagnosis.

Age-related modifications of macrophages influenced by “inflammageing”in graft vs. host disease

Most studies focus on the adaptive immune cells in the GVHD pathogenesis,while little is known about innate immune cells in GVHD occurrence and development,especially macrophages.Meanwhile,a higher incidence of graft versus host disease(GVHD)is also found in the elderly patients.Though advances have been made in the modification of macrophages influenced by the inflamm-ageing,there is still no review on the role of macrophages in GVHD and the association between GVHD and the altered macrophages by inflamm-ageing.In this review,we focus on the potential age-related modifications of macrophage in GVHD,which contributes to the change of morbidity and mortality of GVHD.Via literature review,we found that the infiltration of macrophages is associated with GVHD and macrophages are modified in inflamm-ageing state,including the proliferation,migration,phagocytosis,antigen presentation,interaction with other immune cells,and pro-fibrosis.We suppose that altered macrophage functions in inflamm-ageing state contribute to GVHD in elderly patients.

Gut microbiome in allogeneic hematopoietic stem cell transplantation and specific changes associated with acute graft vs host disease

Allogeneic hematopoietic stem cell transplantation(aHSCT)is a standard validated therapy for patients suffering from malignant and nonmalignant hematological diseases.However,aHSCT procedures are limited by potentially life-threatening complications,and one of the most serious complications is acute graft-versus-host disease(GVHD).During the last decades,DNA sequencing technologies were used to investigate relationship between composition or function of the gut microbiome and disease states.Even if it remains unclear whether these microbiome alterations are causative or secondary to the presence of the disease,they may be useful for diagnosis,prevention and therapy in aHSCT recipients.Here,we summarized the most recent findings of the association between human gut microbiome changes and acute GVHD in patients receiving aHSCT.

Esophageal stenosis with sloughing esophagitis:A curious manifestation of graft-vs-host disease

We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years,complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies confirmed the diagnosis of graft-vs-host disease(GVHD). Balloon dilation,corticosteroids and cyclosporin resulted in marked clinical improvement. Gastrointestinal tract is involved in the majority of patients with chronic GVHD. Esophageal manifestations are rare and include vesiculobullous disease,ulceration,esophageal webs,casts or strictures. Sloughing esophagitis along with severe stenosis requiring endoscopic dilation has never been reported in this context.

Ruxolitinib add-on in corticosteroid-refractory graft-vs-host disease after allogeneic stem cell transplantation:Results from a retrospective study on 38 Chinese patients

BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.METHODS We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation.Ruxolitinib was administered5-10 mg/d depending on disease severity,patient status,and the use of antifungal drugs.Overall response rate,time to best response,malignancy relapse rate,infection rate,and treatment-related adverse events were assessed.RESULTS The analysis included 10 patients with SR-aGVHD (gradeⅢ/Ⅳ,n=9) and 28patients with SR-cGVHD (moderate/severe,n=24).For the SR-aGVHD and SRcGVHD groups,respectively:Median number of previous GVHD therapies was 2(range:1-3) and 2 (1-4);median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo;median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo;and overall response rate was 100%(complete response:80%) and 82.1%(complete response:10.7%) with a response observed in all GVHD-affected organs.The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0%and 10.7%,respectively.Reactivation rates for cytomegalovirus,Epstein-Barr virus,and varicella-zoster virus,respectively,were 30.0%,10.0%,and 0%for the SR-aGVHD group and 0%,14.3%,and 7.1%for the SR-cGVHD group.CONCLUSION Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.

Oral graft vs host disease:An immune system disorder in hematopoietic cell transplantation

Graft vs host disease(GVHD) is a complication of patients who are treated by hematopoietic cell transplantation.National Institutes of Health in 2005 by Working Group on Diagnosis and Staging Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD(cGVHD) established 2 principal categories of oral GVHD, acute and chronic. The oral mucosa may be the first site of manifestation of the disease. Clinical diagnosis needs to be confirmed by a biopsy of oral mucosa and minor salivary glands. Microscopic results have played a major role in the diagnosis and management of acute and chronic oral GVHD. Development of second malignancies is the greatest risk of oral cGVHD patients, mostly regarding squamous cell carcinoma. The focus of oral GVHD therapy is to improve symptoms and maintain oral function. The aim of this review article is to update the information on the oral GVHD in its clinical, microscopic features and their complications.

Immunophenotypic characteristics of multipotent mesenchymal stromal cells that affect the efficacy of their use in the prevention of acute graft vs host disease

BACKGROUND Multipotent mesenchymal stromal cells(MSCs)are widely used in the clinic due to their unique properties,namely,their ability to differentiate in all mesenchymal directions and their immunomodulatory activity.Healthy donor MSCs were used to prevent the development of acute graft vs host disease(GVHD)after allogeneic bone marrow transplantation(allo-BMT).The administration of MSCs to patients was not always effective.The MSCs obtained from different donors have individual characteristics.The differences between MSC samples may affect their clinical efficacy.AIM To study the differences between effective and ineffective MSCs.METHODS MSCs derived from the bone marrow of a hematopoietic stem cells donor were injected intravenously into allo-BMT recipients for GVHD prophylaxis at the moment of blood cell reconstitution.Aliquots of 52 MSC samples that were administered to patients were examined,and the same cells were cultured in the presence of peripheral blood mononuclear cells(PBMCs)from a third-party donor or treated with the pro-inflammatory cytokines IL-1β,IFN and TNF.Flow cytometry revealed the immunophenotype of the nontreated MSCs,the MSCs cocultured with PBMCs for 4 d and the MSCs exposed to cytokines.The proportions of CD25-,CD146-,CD69-,HLA-DR-and PD-1-positive CD4+and CD8+cells and the distribution of various effector and memory cell subpopulations in the PBMCs cocultured with the MSCs were also determined.RESULTS Differences in the immunophenotypes of effective and ineffective MSCs were observed.In the effective samples,the mean fluorescence intensity(MFI)of HLAABC,HLA-DR,CD105,and CD146 was significantly higher.After MSCs were treated with IFN or cocultured with PBMCs,the HLA-ABC,HLA-DR,CD90 and CD54 MFI showed a stronger increase in the effective MSCs,which indicated an increase in the immunomodulatory activity of these cells.When PBMCs were cocultured with effective MSCs,the proportions of CD4+and CD8+central memory cells significantly decreased,and the proportion of CD8+CD146+lymphocytes increased more than in the subpopulations of lymphocytes cocultured with MSC samples that were ineffective in the prevention of GVHD;in addition,the proportion of CD8+effector memory lymphocytes decreased in the PBMCs cocultured with the effective MSC samples but increased in the PBMCs cocultured with the ineffective MSC samples.The proportion of CD4+CD146+lymphocytes increased only when cocultured with the inefficient samples.CONCLUSION For the first time,differences were observed between MSC samples that were effective for GVHD prophylaxis and those that were ineffective.Thus,it was shown that the immunomodulatory activity of MSCs depends on the individual characteristics of the MSC population.

Noninvasive tools based on immune biomarkers for the diagnosis of central nervous system graft-vs-host disease:Two case reports and a review of the literature

BACKGROUND Central nervous system graft-vs-host disease(CNS-GVHD)is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation.Currently,establishing a diagnosis of CNS-GVHD is challenging because the diagnostic criteria and diagnostic methods are not well defined and many confounding factors need to be ruled out.CASE SUMMARY Here,we present two patients with CNS-GVHD.Both patients with a history of acute GVHD or chronic GVHD developed neurological symptoms that could not be explained by other causes,and had abnormal cerebrospinal fluid(CSF)studies as determined by CSF and blood immune biomarker examinations,suggestive of suspected CNS-GVHD.Due to the lack of specific magnetic resonance imaging abnormalities and the rapid clinical deterioration of the patients,we did not attempt to perform a brain biopsy,but prompted the initiation of empirical immunosuppressive therapy.In view of the rapid and favorable response to local and systematic immunosuppressive treatment and the aforementioned neurologic manifestations together with CSF abnormalities and other negative findings,a final diagnosis of CNS-GVHD was made.CONCLUSION CSF and blood immune biomarker examinations facilitated the diagnosis of CNSGVHD,which are particularly suitable for patients who are critically ill and require urgent treatment and for those who are unsuitable for invasive diagnostic procedures.

Fulminant gastrointestinal graft-versus-host disease concomitant with cytomegalovirus infection:Case report and literature review

Here,we report a case of fulminant gastrointestinal graft-versus-host disease(GI-GVHD) with cytomegalovirus(CMV) infection in 44-year-old woman.Despite the difficulties associated with the treatment of GIGVHD and GI-CMV disease,the mucosal findings and the clinical course showed marked improvements during long-term clinical observation.The endoscopic findings were remarkable,with diffuse sloughing mucosa in the stomach and highly active inflammation and deep discrete ulcers throughout the colon.Changes in the CMV quantitative polymerase chain reaction results were correlated with the endoscopic mucosal findings and were useful for assessing the efficacy of the treatment.Although a definite diagnosis of GI-GVHD is generally made by endoscopy with biopsy,the gross appearance of this disease can vary depending on the endoscopy.In this paper,we also conduct a literature review of patients with GI-GVHD.

Advantageous tactics with certain probiotics for the treatment of graft-versus-host-disease after hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complications such as graft-versus-host disease(GVHD)which is a major cause of morbidity and mortality after allogeneic HSCT.It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids(SCFAs)such as butyrate in the experimental models of GVHD after allogeneic HSCT.Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis,increasing the risk of GVHD.Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria,which might be associated with the biology of regulatory T cells(Tregs).Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT.Here,we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity,which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.

Gene and protein expression of proteinase-activated receptor-1, 2 in a murine model of acute graft vs host disease

Proteinase-activated receptors(PARs)are a novel subclass of seven transmembrane-spanning,G protein-coupled receptors.PAR-1 and PAR-2 are widely expressed in a variety of cells and are found to be involved in many physiological and pathological processes includ-ing inflammation and immune response.However,little is known about the function of PAR-1,2 in acute graft vs host disease(GVHD).In the present study,wefirst detected the expression of PAR-1,2 protein and mRNA in a murine model of acute GVHD using the methods of immunohis-tochemistry,Western blot and quantitative real-time polymerase chain reaction(PCR).Syngeneic hematopoie-tic stem cell transplantation(HSCT)mice served as controls.The relative gene expression level of PAR-1 was significantly increased in the skin,liver,small intestine of allogeneic HSCT mice(in skin:0.039�0.013 vs 0.008�0.002 of controls,P=0.009;in liver:0.165�0.006 vs 0.017�0.006 of controls,P=0.004;in small intestine:0.215�0.009 vs 0.016�0.002 of con-trols,P=0.003),but not in the stomach,lung and kidney of allogeneic HSCT mice(P>0.05).PAR-2 mRNA expression in the liver and small intestine of allogeneic HSCT mice(in liver:0.010�0.002 vs 0.003�0.001 of controls,P=0.008;in small intestine:0.006�0.001 vs 0.003�0.001 of controls,P=0.024)was increased significantly,but PAR-2 mRNA expression in the other organs(P>0.05)was not found to be significantly elevated.PAR-1,2 protein expression was in accordance with the mRNA expression,as shown by Western blot.Using immunohistochemistry the present study demon-strated that there was strong PAR-1,2 immunoreactivity in the epithelial cell and vascular endothelial cell of target organs of acute GVHD.Ourfindings of markedly increased expression of PAR-1,2 in target organs of acute GVHD suggest that PAR-1 and PAR-2 may play an important role in the pathogenesis of acute GVHD.

allo-HSCT后淋巴细胞亚群重建与GVHD及感染的相关性

目的探讨血液病病人异基因造血干细胞移植(allo-HSCT)后外周血淋巴细胞各亚群的重建规律,以及淋巴细胞各亚群变化与移植后移植物抗宿主病(GVHD)及感染的关系。方法采用流式细胞术,检测32例allo-HSCT病人清髓处理前3 d和移植后14、30、90、180、365、730 d时的淋巴细胞亚群分布情况,并分析病人GVHD以及感染与淋巴细胞各亚群变化的关系。结果与移植前比较,血液病病人移植后总淋巴细胞、CD3^(+)T细胞、CD4^(+)T细胞、CD8^(+)T细胞、CD16^(+)CD56^(+)NK细胞、CD19^(+)B细胞重建的速度不同,其中NK细胞恢复最快,不到30 d就恢复至移植前水平;其次为CD8^(+)T细胞,约30 d恢复至移植前水平;CD3^(+)T细胞在移植后60 d基本可以达到移植前水平;而B细胞以及CD4^(+)T细胞恢复较慢,B细胞约360 d恢复至移植前水平,CD4^(+)T细胞在移植后730 d仍未恢复到移植前水平。移植后第90天,发生急性移植物抗宿主病(aGVHD)病人5例,其CD3^(+)T细胞(t’=3.334,P<0.05)、CD4^(+)T细胞(t=3.836,P<0.05)和CD16^(+)CD56^(+)NK细胞(t=3.300,P<0.05)绝对计数均低于非急性移植物抗宿主病(non-aGVHD)组,差异有统计学意义。移植后第365天,发生慢性移植物抗宿主病(cGVHD)病人17例,其CD4^(+)T细胞计数低于非慢性移植物抗宿主病(non-cGVHD)组,差异有统计学意义(t=2.918,P<0.05)。与无感染组(n=5)比较,移植后第180天病毒感染组(n=6)淋巴细胞(t=2.441,P<0.05)、CD4^(+)T细胞(t=3.513,P<0.05)、NK细胞(t=3.728,P<0.05)、B细胞(t=2.937,P<0.05)降低;细菌感染组(n=8)淋巴细胞(t=2.535,P<0.05)、CD4^(+)T细胞(t’=6.726,P<0.05)降低,CD8^(+)T细胞升高(t’=-2.945,P<0.05);真菌感染组(n=4)CD4^(+)T细胞降低(t=2.579,P<0.05),CD8^(+)T细胞升高(t=2.423,P<0.05);混合感染组(n=9)淋巴细胞(t=2.195,P<0.05)、CD3^(+)T细胞(t=2.649,P<0.05)、CD4^(+)T细胞(t=3.728,P<0.05)、CD8^(+)T细胞(t=2.579,P<0.05)、B细胞(t=3.045,P<0.05)和NK细胞(t=2.207,P<0.05)绝对计数均降低。结论allo-HSCT后淋巴细胞各亚群的重建以及变化与病人预后相关,应该连续监测病人移植前后外周血淋巴细胞亚群的变化情况。

儿童苔藓样肉芽肿性口炎1例报道及文献回顾

目的探讨口腔苔藓样损害的分类、临床表现、诊断、鉴别诊断及治疗,为临床提供参考。方法获得医院伦理审批及患者知情同意,报道1例儿童口腔苔藓样损害病例,结合文献对口腔苔藓样损害的诊疗进行回顾分析。结果患儿舌背反复破溃伴疼痛3年余,舌背大面积糜烂面,形状不规则,糜烂周围见珠光白色纹,左侧糜烂区伴组织增生,约1.5 cm×2.0 cm,质地韧,宽蒂。舌背白色网纹组织切取活检病理诊断为苔藓样损害;舌背增生物切除活检病理诊断为苔藓样损害伴肉芽肿性炎。根据患者口内损害特征、系统病史、用药史、组织病理学检查结果,最终诊断为苔藓样肉芽肿性口炎。文献回顾表明,口腔苔藓样损害病因不明,临床上需与口腔扁平苔藓、口腔苔藓样药物反应、口腔苔藓样接触性损害、慢性溃疡性口炎等疾病鉴别。临床上治疗口腔苔藓样损害以糖皮质激素的局部和/或全身使用为主。结论目前口腔苔藓样损害的分类和诊断仍无统一标准,主要依靠病史询问、临床表现和组织病理学检查结果,治疗方法主要为糖皮质激素的局部和/或全身使用。

三级淋巴结构在器官移植排斥反应中的现状与展望

器官移植后,移植物的排斥反应是最常见的并发症之一,无论病因如何都会对移植物产生不良损害。三级淋巴结构(TLS)于病理情况下非淋巴组织内发生。针对调节移植物排斥反应的机制鉴定和表征,不仅能够促进人们对器官移植物的存活及预后的理解,而且还为治疗移植物排斥反应提供了思路。

HLA配型不合情况下造血干细胞移植的新方法

目的 :采用新方法进行非体外去除T细胞的人类白细胞抗原 (humanleukocyteantigen ,HLA)配型不合造血干细胞移植。方法 :5 8例血液恶性肿瘤患者 ,33例为高危或难治复发白血病 ,接受了至少一个HLA位点不合的家庭供者造血干细胞移植。移植物为经粒细胞集落刺激因子 (granulocyteclony stimulatingfactor ,G CSF)动员的骨髓以及外周血造血干细胞 ,而无需体外去除T细胞。移植物抗宿主病 (graft versus host disease,GVHD)预防采用环孢菌素A +霉酚酸酯 +短程甲氨喋呤方案。结果 :所有患者均获得持久、完全供者植入。 5 8例患者中发生Ⅱ度及以上急性GVHD 2 2例 (37.9% ) ,其中Ⅲ度和Ⅳ度急性GVHD分别为 2例和 1例 ,其严重程度与HLA不合程度无相关 ;4 2例可评估患者中 ,慢性GVHD为 2 6例 (6 1.9% ) ,广泛型和局限型分别为 11例和 15例。复发 9例 ,除 1例外均为复发、难治白血病患者。死亡 14例 ,其中 7例死于疾病复发 ,另 7例死于移植相关合并症 ,其中严重感染和间质性肺炎各 2例 ,巨细胞病毒性脑炎、病毒型肝炎和急性GVHD死亡各 1例。中位随访 10月 (2～ 37.5月 ) ,5 8例患者中 4 2例无病存活 (disease freesurvival,DFS) ,高危患者 2年DFS明显低于标危患者 ,分别为 6 3.2 %和 77.6 % (P =0 .0 4 )。DFS与供受?

异基因造血干细胞移植后肺炎的病因分析

目的:分析异基因造血干细胞移植后肺炎的临床特点和病因谱。方法:总结北京大学血液病研究所1998至 2001连续 4年中 255例异基因造血干细胞移植受者中发生移植后肺炎的资料。结果: 66例发生移植后肺炎的患者累计发病 72例次,总发病率 25. 9%; 50例患者的移植后肺炎被治愈,占 75%。病因分析显示,细 /真菌感染性移植后肺炎 12例次(16. 7% ),巨细胞病毒性肺炎 22例次(30. 6% ),特发性肺炎综合征 36例次(50. 0% )。总死亡率为 22. 7%。发生特发性肺炎综合征的患者较多伴发慢性移植物抗宿主病,免疫抑制剂治疗有效。结论:异基因造血干细胞移植后肺炎是移植后常见的合并症,其病因学包括感染和非感染因素,针对病因的治疗可以改善预后。

单倍型异基因造血干细胞移植治疗重型再生障碍性贫血:回顾性分析

背景:随着国内独生子女家庭的普及,全相合造血干细胞移植受干细胞来源限制,临床应用受到局限,因此单倍型造血干细胞移植越来受到亲睐。目的:回顾性对比分析单倍型异基因造血干细胞移植和全相合异基因造血干细胞移植治疗重型再生障碍性贫血的临床疗效及安全性。方法:选取解放军北京军区总医院血液科2013年1月至2015年1月接受单倍型异基因造血干细胞移植治疗的15例重型再生障碍性贫血患者(治疗组)病例资料,预处理方案为环磷酰胺、氟达拉滨、白舒非联合抗人淋巴细胞免疫球蛋白,供者接受粒细胞集落刺激因子动员,移植方式应用骨髓联合外周血干细胞移植。采用联合免疫抑制剂包括环孢素A、甲氨蝶呤、他克莫司等预防移植物抗宿主病。同时选择同期行全相合异基因造血干细胞移植治疗的15例重型再生障碍性贫血患者病例资料作为对照组,统计两组患者移植相关并发症及存活情况。结果与结论:随访至2015年7月,治疗组中位随访时间20.7个月(6-30个月),全部患者均获造血重建,4例发生移植物抗宿主病、5例合并肺部感染、3例合并败血症,因肺部感染死亡1例、败血症死亡1例、移植物抗宿主病死亡2例;对照组中位随访时间19.7个月(5-28个月),全部患者均获造血重建,3例发生移植物抗宿主病、4例合并肺部感染,因移植物抗宿主病死亡2例、肺部感染死亡1例,两组患者总生存率分别为73%和80%,差异无显著性意义(P=0.67)。结果表明单倍型移植治疗重型再生障碍性贫血安全有效,临床疗效与全相合造血干细胞移植相当。

异体肾移植^（99m）Tc－DTPA肾动态显像的实验研究及临床应用

通过狗异体肾移植动态肾显像的研究，为临床应用提供依据．方法：建立标准狗异体肾移植模型，以９９ｍＴｃ-ＤＴＰＡ为示踪剂，对１５条狗异体肾移植后进行肾动态显像监测．结果：稳定期（ｎ＝１０）肾显像清晰，移植肾高峰计数／主动脉高峰计数（Ｋ／Ａ）均值３．６５±１．１８．２０分钟膀胱／移植肾放射性计数（Ｂ／Ｋ））比值＞１（１００％）；排异早期（ｎ＝１０）肾显像清晰．Ｋ／Ａ均值１．９８±０．６７（Ｐ＜０．０１），肾清除核素速率明显降低，Ｂ／Ｋ比值＜１（１００％）；排异晚期（ｎ＝１０）肾显像差，膀胱不显像．临床检查８例肾移植病人，正常肾动态显像３例，包括１例自体肾移植和１例异体肾移植，两者肾功能均正常，１例急性排异早期，用大剂量糖皮质激素冲击疗法３天，肾恢复利尿但血Ｃｒ尚未恢复正常；异常肾动态显像５例，其中２例急性排异病情较轻和２例严重急性排异病人，肾动态显像表现分别与上述动物实验的排异早、晚期的异常显像相符，１例并发急性尿路梗阻病人移植肾血流灌注正常，排泄受阻，功能相呈梗阻型．结论：９９ｍＴｃ-ＤＴＰＡ肾动态显像的Ｂ／Ｋ比值能发现早期排异的肾功能异常，Ｋ／Ａ比值反映肾血流灌注情况．与排异的严重程度相关；该检查还能早期反映抗?

慢性移植物抗宿主病狼疮小鼠肾组织Akt信号通路蛋白表达及泼尼松的调控作用

目的 :研究慢性移植物抗宿主病 (GvHD)狼疮小鼠肾组织Akt信号通路蛋白在体内是否存在异常活化及泼尼松对Akt信号通路蛋白活化的调控作用。方法 :肾组织Akt和磷酸化IκBα蛋白检测采用Westernblot方法 ,NF -κB活性检测采用电泳迁移率改变实验 (EMSA)。结果 :注射单细胞悬液后第 8周和第 1 2周 ,狼疮鼠肾组织Akt活性、磷酸化IκBα及NF -κB活性均显著高于正常对照组 (P <0 0 5) ,第 1 6周 ,狼疮鼠肾组织Akt活性、磷酸化IκBα及NF -κB活性均与正常对照组无显著差别 (P >0 0 5) ;第 8周和第 1 2周时 ,狼疮小鼠肾组织Akt活性与NF -κB活性均呈正相关 (分别为r=0 52 3和r =0 574 ,P <0 0 5)。泼尼松对狼疮小鼠外周血抗dsDNA抗体滴度和尿蛋白具有显著的抑制作用 ,对肾脏病理改变有显著的改善作用 ,同时 ,泼尼松亦显著抑制狼疮小鼠肾组织Akt活性、磷酸化IκBα和NF -κB活性。结论 :GvHD狼疮小鼠肾组织存在Akt-NF -κB信号通路异常活化 ,泼尼松对该模型具有治疗作用可能与其抑制体内Akt-NF -κB信号通路异常活化有关。