国产抗胸腺/淋巴细胞球蛋白联合环孢素A治疗非重型再生障碍性贫血的临床观察

目的 探讨国产ATG/ALG联合环孢素A在治疗非重型再生障碍性贫血中的临床疗效及不良反应.方法 回顾性分析我院自2005年1月至2010年10月应用ATG/ALG联合环孢素A治疗的经环孢素A、雄激素和中药联合治疗6个月以上无效或复发的非重型再生障碍性贫血患者的临床资料.结果 国产ATG( ALG-P)治疗总有效率61....     

Poor kidney allograft survival associated with positive B cell – Only flow cytometry cross matches: A ten year single center study

The presence of donor specific antibody (DSA) to class 1 or class 2 HLA as detected respectively in T cell or B cell – only flow cytometry cross matches (FCXMs) are risk factors for renal allograft survival, though the comparative risk of these XMs has not been definitively established. Allograft survival and FCXM data in 624 microcytotoxicity (CDC) XM negative kidney transplants were evaluated. Short and long term allograft survival was significantly less in recipients with T⁻ B⁺ FCXMs (1 year, 74%, 10 year, 58%) compared to T⁺ B⁺ FCXMs (1 year, 84%, 10 year, 68%) and to T⁻ B⁻ FCXM (1 year, 90%, 10 year, 85%). Risk factors were positive FCXM, deceased donor (DD) transplantation and donor age, but not race, gender, recipient age or previous transplant. Recipients with T⁻ B⁺ and T⁺ B⁺ FCXMs were at 4.5 and 2.5 fold greater risk, respectively, of DD allograft failure compared to patients with T⁻ B⁻ FCXMs. The quantitative value of FCXM did not correlate with the duration of graft survival. We conclude that patients with DSA to class 2 HLA have a greater risk of early and late allograft failure compared to patients with DSA to class 1 HLA.     

Localization and Biodistribution of Conjugate ATG－Dex－DNR in Nude Mice as Models for Human Leukemia

ＬｏｃａｌｉｚａｔｉｏｎａｎｄＢｉｏｄｉｓｔｒｉｂｕｔｉｏｎｏｆＣｏｎｊｕｇａｔｅＡＴＧ－Ｄｅｘ－ＤＮＲｉｎＮｕｄｅＭｉｃｅａｓＭｏｄｅｌｓｆｏｒＨｕｍａｎＬｅｕｋｅｍｉａＺＨＡＮＧＤｏｎｇ－ｈｕａ（张东华），ＴＡＮＧＪｉｎ－ｚｈｉ（唐锦治），ＬＩＺ...     

Long noncoding RNA DANCR confers cytarabine resistance in acute myeloid leukemia by activating autophagy via the miR‐874‐3P/ATG16L1 axis

Autophagy is an important mechanism involved in the regulation of acute myeloid leukemia (AML) chemoresistance. The long noncoding RNA (lncRNA) differentiation antagonizing non‐protein coding RNA (DANCR) exhibits oncogenic activity in several types of human cancers, including AML, but it remains unclear whether it regulates autophagy and chemoresistance in AML. We report here that cytarabine (Ara‐C) treatment elevates DANCR expression in human AML cells. In addition, DANCR overexpression confers and its knockdown diminishes Ara‐C resistance in human AML cells, suggesting that DANCR positively regulates AML chemoresistance to Ara‐C. Moreover, DANCR promotes autophagy in Ara‐C‐treated human AML cells and acts as a sponge to decrease miR‐20a‐5p expression, thereby upregulating the expression of ATG16L1, a critical component of the autophagy machinery. Importantly, ATG16L1 silencing abrogates DANCR‐promoted autophagy and markedly restores DANCR‐conferred Ara‐C resistance, suggesting that DANCR promotes MIR‐874‐3P/ATG16L1 axis‐regulated autophagy to confer Ara‐C resistance in human AML cells. Together, this study identifies DANCR as a positive regulator of Ara‐C resistance in human AML cells, suggesting this lncRNA as a potential target for overcoming Ara‐C resistance in AML chemotherapy.     

Regulatory T cells for tolerance

Regulatory T cells (Tregs) are critical mediators of immune homeostasis and hold significant promise in the quest for transplantation tolerance. Progress has now reached a critical threshold as techniques for production of clinical therapies are optimised and Phase I/II clinical trials are in full swing. Initial safety and efficacy data are being reported, with trials assessing a number of different strategies for the introduction of Treg therapy. It is now more crucial than ever to elucidate further the function and behaviour of Tregs in vivo and ensure safe delivery. This review will discuss the current state of the art and future directions in Treg therapy.     

Increased T cell immunosenescence and accelerated maturation phenotypes in older kidney transplant recipients

Older kidney transplant recipients experience increased rates of infection and death, and less rejection, compared with younger patients. However, little is known about immune dysfunction in older compared with younger kidney transplant recipients and whether it is associated with infection. We evaluated T cell phenotypes including maturation, immune senescence, and exhaustion in a novel investigation into differences in older compared with younger patients receiving identical immune suppression regimens.We evaluated PBMC from 60 kidney transplant recipients (23 older and 37 matched younger patients) by multiparameter immune phenotyping. Older kidney transplant recipients demonstrated decreased frequency of naïve CD4+ and CD8+ T cells, and increased frequency of terminally differentiated, immune senescent, and NK T cells expressing KLRG1. There was a trend towards increased frequency of T cell immune senescence in patients experiencing infection in the first year after transplantation, which reached statistical significance in a multivariate analysis.This pilot study reveals immune dysfunction in older compared with younger transplant recipients, and suggests a likely mechanism for increased vulnerability to infection. The ability to assess T cell maturation and immune senescence in transplant recipients offers the potential for risk stratification and customization of immune suppression to prevent infection and rejection after transplantation.     

Preclinical and clinical studies for transplant tolerance via the mixed chimerism approach

Based upon observations in murine models, we have developed protocols to induce renal allograft tolerance by combined kidney and bone marrow transplantation (CKBMT) in non-human primates (NHP) and in humans. Induction of persistent mixed chimerism has proved to be extremely difficult in major histocompatibility complex (MHC)-mismatched primates, with detectable chimerism typically disappearing within 30–60?days. Nevertheless, in MHC mismatched NHP, long-term immunosuppression-free renal allograft survival has been achieved reproducibly, using a non-myeloablative conditioning approach that has also been successfully extended to human kidney transplant recipients. CKBMT has also been applied to the patients with end stage renal disease with hematologic malignancies. Renal allograft tolerance and long-term remission of myeloma have been achieved by transient mixed or persistent full chimerism. This review summarizes the current status of preclinical and clinical studies for renal and non-renal allograft tolerance induction by CKBMT. Improving the consistency of tolerance induction with less morbidity, extending this approach to deceased donor transplantation and inducing tolerance of non-renal transplants, are critical next steps for bringing this strategy to a wider range of clinical applications.     

自噬与沉默信息调节因子蛋白家族对心肌缺血/再灌注的影响

背景自噬是一种细胞本体的降解过程.它以溶酶体的方式参与或老化非正常的细胞蛋白及细胞本身的降解.许多研究证实自噬水平在心肌缺血/再灌注(ischemia/reperfusion,I/R)中增高,但对于自噬在再灌注中的作用,现在争议较大.同时有研究证实新发现的与长寿相关的沉默信息调节因子蛋白(silent information regulator protein,Sirt)家族可能参与了自噬对I/R的调节.目的了解Sirt家族、自噬及I/R这三者间的联系.内容对自噬的基本过程,自噬的分子机制,自噬在心肌I/R中的作用,自噬与Sirt家族的关系作一综述.趋向促进对自噬的深入了解,期望对Sirt家族在心肌保护方面的作用提供新的认识.     

肾移植术后应用抗胸腺细胞球蛋白的价值与前景(64例次随访分析)

目的：探讨抗胸腺细胞球蛋白（ＡＴＧ），在肾移植术后的应用价值与前景。方法：对６４例次使用ＡＴＧ的肾移植受者进行回顾性分析，比较其①对急性排异反应（ＡＲ）、急性加速性排异反应（ＡＡＲ）、超急性排异反应（ＨＡＲ）的预防与治疗情况；②对部分肾移植术后因各种原因暂不能使用常规免疫抑制剂者的替代与过渡治疗情况；③获得以上各种情况的治疗总剂量与总时限。结果：①ＡＴＧ对肾移植术后ＡＲ的逆转率为８２．３５％（１４／１７），对耐激素性ＡＲ的逆转率为７８．５７％（１１／１４），对ＡＡＲ的逆转率为１００％（１０／１０）；②ＡＴＧ制品适用于肾移植术后因各种原因暂不能服用常规免疫抑制剂者的替代与过渡治疗；③ＡＴＧ对ＨＡＲ不能起到预防与治疗的作用；④抗ＡＲ的ＡＴＧ治疗总剂量与时限以８００ｍｇ、５天为宜，抗ＡＡＲ的ＡＴＧ治疗总剂量与时限以７００ｍｇ、６天为宜，预防与替代治疗的总剂量与时限以７００ｍｇ、６天为宜。结论：ＡＴＧ适用于肾移植术后ＡＲ与ＡＡＲ的预防与治疗，特别对耐激素性排异反应以及暂时的替代与过渡治疗尤为合适，如果经济状况允许，应提倡使用。     

The role of CD45RO in antithymocyte globulin's stimulation of primitive haemopoietic cells

Summary. We have found that antithymocyte globulin (ATG), an equine antibody with proven efficacy in aplastic anaemia (AA), has a direct stimulatory effect on primitive haemopoietic cells from normal donors. This growth stimulation may be mediated via anti-CD45RO activity present in the ATG preparation. Addition of unabsorbed ATG enhanced colony growth at 21 d in the blast colony forming cell (Bl-CFC) assay. Prior absorption of ATG by incubation with the CD45RO⁺ MOLT-4 cell line resulted in the loss of enhancement. Absorption by MOLT-4 cells preincubated with anti-CD45RO mAb, UCHL-1, restored ATG's stimulatory effect. The Bl-CFC could also be stimulated to grow by the addition of UCHL-1 directly. Incubation of the primitive haemopoietic cells for 4 h with ATG was associated with a decline in the antigenic density of CD45RO, a tyrosine phosphatase. This down-regulation may upset the balance between growth factor-induced tyrosine kinase activation and tyrosine phosphate dephosphorylation resulting in increased growth of primitive cells. a possible factor in the sustained recovery of haemopoiesis seen in AA patients after ATG treatment.