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HLA and lung transplantation

Liya Ju, Caroline Suberbielle, Xiaofan Li, Nuala Mooney, Dominique Charron

《医学前沿（英文）》 2019年 第13卷 第3期   页码 298-313 doi: 10.1007/s11684-018-0636-x

摘要： Lung transplantation is increasingly practiced for patients with end-stage lung disease. The successful outcome of solid organ transplantation today is severely impeded by the production of alloantibodies, mainly directed against the protein products of the HLA complex of the organ donor. While the association between antibody mediated rejection and allograft damage has been well established in renal and heart transplantation, it has not yet been well characterized in lung transplantation. This review addresses the question of HLA matching in lung transplantation and current knowledge of the allogenicity of different HLA class I and II antigens. The role of the antibody mediated immune response is discussed as well as the importance of pre-transplant or post-transplant circulating antibodies. Finally, potential mechanisms, which may act individually or in combination, of antibody mediated damage to solid organ transplants are considered.

关键词： human leukocyte antigen class I and II     lung transplantation     mismatch     obliterans bronchiolitis     alloantibody     antibody mediated rejection    

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DQB1*060101 may contribute to susceptibility to immunoglobulin A nephropathy in southern Han Chinese

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 507-516 doi: 10.1007/s11684-016-0475-6

摘要：

Immunoglobulin A nephropathy (IgAN) is a common form of chronic glomerulonephritis with unknown pathogenesis. Accumulating evidences have shown the ethnic-specific association between certain human leukocyte antigen (HLA) alleles and IgAN susceptibility. This study was designed to explore the relationship between HLA-DQB1 alleles and disease susceptibility and clinical manifestations of patients with IgAN in southern Han Chinese. A PCR sequence-based typing technique was used to detect HLA-DQB1 alleles in 217 IgAN patients and 229 healthy subjects. Clinical data were collected from each patient at the time of renal biopsy. Twenty HLA-DQB1 alleles were detected in IgAN patients and healthy subjects. High frequency of HLA-DQB1*060101 and low frequency of HLA-DQB1*030101 were observed in IgAN patients compared with healthy controls. Further stratification analysis revealed that the frequency of DQB1*060101 was significantly higher in patients with urine protein≥1.0 g/24 h than in patients with urine protein<1.0 g/24 h. In combination with our previous DRB1 results, we also analyzed the association of DRB1-DQB1 haplotypes with IgAN. We found that the frequency of haplotype DRB1*090102-DQB1*060101 was significantly higher [odds ratio (OR) = 4.409, Pc = 0.016], whereas that of HLA-DRB1*070101-DQB1*020101 was significantly lower (OR= 0.194, Pc = 0.016) compared with healthy controls. Our study indicated that HLA-DQB1*060101 alleles may be a potential predictor of high-risk IgAN susceptibility in Chinese Han population.

关键词： DQB1     human leukocyte antigen (HLA)     IgA nephropathy     haplotype     association study    

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Advancement of human leukocyte antigen-partially matched related hematopoietic stem cell transplantation

null

《医学前沿（英文）》 2013年 第7卷 第3期   页码 306-315 doi: 10.1007/s11684-013-0279-x

摘要：

Allogeneic hematopoietic stem cell transplantation (HSCT) is one of the most effective options for hematological malignancies, and human leukocyte antigen-partially matched related donors (PMRDs) are a valuable option for HSCT. Several protocols (with or without ex vivo T-cell depletion (TCD)) have been established worldwide. TCD including CD34+positive selection and CD3/CD19 depletion has successfully overcome the human leukocyte antigen disparity. However, TCD is associated with prolonged immune deficiencies, increased risks of infectious complications, and high transplantation-related mortality. PMRD HSCT without ex vivo TCD is well developed, and numerous patients have benefitted from it. Here, we review the literature on PMRD HSCT.

关键词： partially matched related donor     hematopoietic stem cell transplantation     allogeneic    

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immune recovery between event-free patients receiving haploidentical allografts and those receiving humanleukocyte antigen-matched sibling donor allografts

null

《医学前沿（英文）》 2018年 第12卷 第2期   页码 153-163 doi: 10.1007/s11684-017-0548-1

摘要：

To establish optimal reference values for recovered immune cell subsets, we prospectively investigated post-transplant immune reconstitution (IR) in 144 patients who received allogeneic stem cell transplantation (allo-SCT) and without showing any of the following events: poor graft function, grades II?IV acute graft-versus-host disease (GVHD), serious chronic GVHD, serious bacterial infection, invasive fungal infection, or relapse or death in the first year after transplantation. IR was rapid in monocytes, intermediate in lymphocytes, CD3+ T cells, CD8+ T cells, and CD19+ B cells, and very slow in CD4+ T cells in the entire patient cohort. Immune recovery was generally faster under HLA-matched sibling donor transplantation than under haploidentical transplantation. Results suggest that patients with an IR comparable to the reference values display superior survival, and the levels of recovery in immune cells need not reach those in healthy donor in the first year after transplantation. We suggest that data from this recipient cohort should be used as reference values for post-transplant immune cell counts in patients receiving HSCT.

关键词： immune reconstitution     hematopoietic stem cell transplantation     event-free patients     reference range    

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嵌合抗原受体和调节性T细胞——移植中人类白细胞抗原特异性免疫抑制的潜力 Review

Sabrina Wright, Conor Hennessy, Joanna Hester, Fadi Issa

《工程（英文）》 2022年 第10卷 第3期   页码 30-43 doi: 10.1016/j.eng.2021.10.018

摘要：

嵌合抗原受体（CAR）是基因工程领域的一项突破，它彻底改变了过继细胞疗法（ACT）领域。表达这些受体的细胞通过在合成的CAR构建体中包含抗原特异性结合区域而被重新定向到预定的靶点。程序化特异性细胞在肿瘤学领域的优势已被临床证明，与同类未修饰的细胞相比，这种细胞具有更高的准确性、效力与更少的脱靶效应。与常规T细胞（Tconvs）不同，调节性T细胞（Treg）在抑制免疫激活和调节宿主免疫反应方面发挥着重要作用。Treg 中CAR的表达被认为是治疗自身免疫和炎症性疾病、移植物抗宿主病（GVHD）和器官移植排斥反应的一种方法。在后者中，它们作为同种异体移植受者免疫耐受的介质具有巨大的潜力。然而，目前对CAR-Treg 工程的研究非常有限，并且关于治疗用途的最佳设计存在不确定性。本文综述了CAR-Treg 发展的理论基础、其对人类移植的意义、潜在的设计、安全性考虑因素，以及迄今为止CAR-Treg在移植模型中的对比。

关键词： 嵌合抗原受体（CAR）     调节性T细胞     异性免疫     CAR设计     基因编辑    

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HLA 分布仿真扩展研究

吴泽彬,吴慧中,李蔚清

《中国工程科学》 2008年 第10卷 第7期   页码 141-146

摘要：

分析HLA 扩展研究现状，针对HLA分布仿真互操作和重用的两个典型问题，结合Web 服务技术，将 传统HLA仿真应用框架进行去耦处理，提出一个HLA 分布仿真扩展体系结构，基于pRTI 和AXIS 引擎实现原 型系统，通过实例详细说明RTI 服务的封装部署以及RTI API 调用到SOAP 消息的映射。该扩展设计能够封 装原有的RTI 库；将传统的HLA 分布仿真应用扩展到广域网环境；具有广泛的兼容能力，可以支持不同的系 统平台，实现松散耦合、跨平台的分布式仿真系统。

关键词： HLA/RTI     分布仿真     Web 服务     SOAP     体系结构    

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Coronary leukocyte activation in relation to progression of coronary artery disease

null

《医学前沿（英文）》 2016年 第10卷 第1期   页码 85-90 doi: 10.1007/s11684-016-0435-1

摘要：

Leukocyte activation has been linked to atherogenesis, but there is little in vivo evidence for its role in the progression of atherosclerosis. We evaluated the predictive value for progression of coronary artery disease (CAD) of leukocyte activation markers in the coronary circulation. Monocyte and neutrophil CD11b, neutrophil CD66b expression and intracellular neutrophil myeloperoxidase (MPO) in the coronary arteries were determined by flow cytometry in patients undergoing coronary angiography. The primary outcome included fatal and nonfatal myocardial infarction or arterial vascular intervention due to unstable angina pectoris. In total 99 subjects who were included, 70 had CAD at inclusion (26 patients had single-vessel disease, 18 patients had two-vessel disease and 26 patients had three-vessel disease). The median follow-up duration was 2242 days (interquartile range: 2142–2358). During follow-up, 13 patients (13%) developed progression of CAD. Monocyte CD11b, neutrophil CD11b and CD66b expression and intracellular MPO measured in blood obtained from the coronary arteries were not associated with the progression of CAD. These data indicate that coronary monocyte CD11b, neutrophil CD11b and CD66b expression and intracellular MPO do not predict the risk of progression of CAD.

关键词： coronary artery disease     inflammation     integrin     myeloperoxidase     leukocyte activation    

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复杂系统计算机仿真的研究与设计

金士尧,李宏亮,党岗,王召福,刘晓建

《中国工程科学》 2002年 第4卷 第4期   页码 52-57

摘要：

复杂系统与复杂性是21世纪的核心科学问题之一，并引入国家重点基础研究发展规划。基于复杂系统的复杂性和不确定性，很难想像可以采用传统朴素的还原论法进行可行性研究。推崇多智能主体的模糊计算机仿真来研究复杂系统的复杂性，并设计了一个基于多智能体的复杂系统分布仿真平台。

关键词： 复杂系统     计算机仿真     Agent     HLA/RTI    

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Chimeric antigen receptor T cell therapies for acute myeloid leukemia

Bin Gu, Jianhong Chu, Depei Wu

《医学前沿（英文）》 2020年 第14卷 第6期   页码 701-710 doi: 10.1007/s11684-020-0763-z

摘要： Abstract Chimeric antigen receptor T cell (CAR T) therapies have achieved unprecedented efficacy in B-cell tumors, prompting scientists and doctors to exploit this strategy to treat other tumor types. Acute myeloid leukemia (AML) is a group of heterogeneous myeloid malignancies. Relapse remains the main cause of treatment failure, especially for patients with intermediate or high risk stratification. Allogeneic hematopoietic stem cell transplantation could be an effective therapy because of the graft-versus-leukemia effect, which unfortunately puts the patient at risk of serious complications, such as graft-versus-host disease. Although the identification of an ideal target antigen for AML is challenging, CAR T therapy remains a highly promising strategy for AML patients, particularly for those who are ineligible to receive a transplantation or have positive minimal residual disease. In this review, we focus on the most recent and promising advances in CAR T therapies for AML.

关键词： acute myeloid leukemia     CAR T     immunotherapy    

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人体前列腺特异性抗原携带含酮基-脱氧壬酮糖酸的N-聚糖 Article

Wei Wang, Tao Zhang, Jan Nouta, Peter A. van Veelen, Noortje de Haan, Theo M. de Reijke, Manfred Wuhrer, Guinevere S.M. Lageveen-Kammeijer

《工程（英文）》 2023年 第26卷 第7期   页码 119-131 doi: 10.1016/j.eng.2023.02.009

摘要：

Ketodeoxynononic acid (Kdn) is a rather uncommon class of sialic acid in mammals. However, associations have been found between elevated concentrations of free or conjugated Kdn in relation to human cancer progression. Hitherto, there has been a lack of conclusive evidence that Kdn occurs on (specific) human glycoproteins (conjugated Kdn). Here, we report for the first time that Kdn is expressed on prostate-specific antigen (PSA) N-linked glycans derived from human seminal plasma and urine. Interestingly, Kdn was found only in an α2,3-linkage configuration on an antennary galactose, indicating a highly specific biosynthesis. This unusual glycosylation feature was also identified in a urinary PSA cohort in relation to prostate cancer (PCa), although no differences were found between PCa and non-PCa patients. Further research is needed to investigate the occurrence, biosynthesis, biological role, and biomarker potential of both free and conjugated Kdn in humans.

关键词： 酮基-脱氧壬酮糖酸     Kdn     糖基化     前列腺癌     前列腺特异性抗原    

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A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma

Houli Zhao, Yiyun Wang, Elaine Tan Su Yin, Kui Zhao, Yongxian Hu, He Huang

《医学前沿（英文）》 2020年 第14卷 第6期   页码 711-725 doi: 10.1007/s11684-020-0808-3

摘要： The combination of the immunotherapy (i.e., the use of monoclonal antibodies) and the conventional chemotherapy increases the long-term survival of patients with lymphoma. However, for patients with relapsed or treatment-resistant lymphoma, a novel treatment approach is urgently needed. Chimeric antigen receptor T (CAR-T) cells were introduced as a treatment for these patients. Based on recent clinical data, approximately 50% of patients with relapsed or refractory B-cell lymphoma achieved complete remission after receiving the CD19 CAR-T cell therapy. Moreover, clinical data revealed that some patients remained in remission for more than two years after the CAR-T cell therapy. Other than the CD19-targeted CAR-T, the novel target antigens, such as CD20, CD22, CD30, and CD37, which were greatly expressed on lymphoma cells, were studied under preclinical and clinical evaluations for use in the treatment of lymphoma. Nonetheless, the CAR-T therapy was usually associated with potentially lethal adverse effects, such as the cytokine release syndrome and the neurotoxicity. Therefore, optimizing the structure of CAR, creating new drugs, and combining CAR-T cell therapy with stem cell transplantation are potential solutions to increase the effectiveness of treatment and reduce the toxicity in patients with lymphoma after the CAR-T cell therapy.

关键词： chimeric antigen receptor T (CAR-T) cell     lymphoma     cytokine release syndrome (CRS)     immune effector cell-associated neurotoxicity syndrome (ICANS)    

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Serum carbohydrate antigen (CA) 19-9 as a prognostic factor in cholangiocarcinoma: A meta-analysis

Shang-Long LIU, Zi-Fang SONG, Qing-Gang HU, Shao-Bo HU, Jun LI, Qi-Chang ZHENG, Duo SHAN,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 457-462 doi: 10.1007/s11684-010-0240-1

摘要： This study was performed to determine the prognostic role of preoperative serum carbohydrate antigen (CA) 19-9 levels in the survival of patients with cholangiocarcinoma. Articles published up to June 1, 2010 that evaluated preoperative CA19-9 levels and the prognosis of cholangiocarcinoma were collected for meta-analysis. The required information for calculating individual relative risk (RR) was extracted from the studies, and a combined overall RR was estimated. Nine eligible studies were included. One study dealt with extra-hepatic cholangiocarcinoma, while the other eight studies analyzed intra-hepatic cholangiocarcinoma. The mean methodological quality score was 74.1%, ranging from 65.5% to 82.5%. The overall RR for the nine studies was 1.28 (95% confidence interval= 1.10–1.46), and the Z-score for overall effect was 13.83 (<0.001). The association between serum CA19-9 level and lymph node involvement was also assessed. The combined RR was 1.471 (95% confidence interval= 0.411–5.264) and Z-score for overall effect was 0.59 ( = 0.553). CA19-9 levels were associated significantly with the prognosis of patients with cholangiocarcinoma. This meta-analysis shows that elevation of preoperative CA19-9 levels is correlated with a poor prognosis of patients with cholangiocarcinoma. However, larger scale and randomized studies are needed to draw a more substantive conclusion.

关键词： cholangiocarcinoma     prognostic factors     serum carbohydrate antigen 19-9    

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CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a

《医学前沿（英文）》 2022年 第16卷 第3期   页码 322-338 doi: 10.1007/s11684-021-0901-2

摘要： Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.

关键词： cancer immunotherapy     chimeric antigen receptor     solid tumors     tumor-associated antigen     glycosylation     O-glycans     adoptive cell therapy    

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Detection and monitoring prostate specific antigen using nanotechnology approaches to biosensing

Grant Perry, Fernando Cortezon-Tamarit, Sofia I. Pascu

《化学科学与工程前沿（英文）》 2020年 第14卷 第1期   页码 4-18 doi: 10.1007/s11705-019-1846-8

摘要： Prostate cancer has a high incidence in men and remains the second cause of mortality due to cancer. As the development of the disease is greatly correlated to age, the identification of novel detection methods reliable, efficient, and cost effective is a matter of significant importance in the ageing population of western societies. The detection of the prostate specific antigen (PSA) in blood samples has been the preferred method for the detection and monitoring of prostate cancer over the past decades. Despite the indications against its use in massive population screening, PSA still remains the best studied biomarker for prostate cancer and the detection of its different forms and incorporation in multiplexed designs with other biomarkers still remains a highly valuable indicator in the theranostics of prostate cancer. The latest developments in the use of nanomaterials towards the construction of PSA biosensors are reviewed hereby. The incorporation of gold nanoparticles, silica nanoparticles and graphene nanostructures to biosensing devices has represented a big leap forward in terms of sensitivity, stability and miniaturization. Both electrochemical and optical detection methods will be reviewed herein for the detection of PSA.

关键词： biosensing     immunosensor     PSA     prostate cancer     fluorescence    

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may affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen

Lili Zhou, Ping Li, Shiguang Ye, Xiaochen Tang, Junbang Wang, Jie Liu, Aibin Liang

《医学前沿（英文）》 2020年 第14卷 第6期   页码 786-791 doi: 10.1007/s11684-020-0751-3

摘要： Factors associated with complete and durable remissions after anti-CD19 chimeric antigen receptor T (CAR-T) cell immunotherapy for relapsed or refractory non-Hodgkin lymphoma (r/r NHL) have not been well characterized. In this study, we found that the different sites of extranodal involvement may affect response, overall survival (OS), and progression-free survival (PFS) in patients with r/r NHL treated with anti-CD19 CAR-T cells. In a cohort of 32 treated patients, 12 (37.5%) and 8 (25%) patients exhibited soft tissue lymphoma and bone marrow (BM) infiltrations, respectively, and 13 (41%) patients exhibited infiltration at other sites. The factors that may affect prognosis were identified through multivariable analysis. As an independent risk factor, soft tissue infiltration was the only factor significantly correlated with adverse prognosis ( <0.05), whereas other factors did not reach statistical significance. Furthermore, the site of extranodal tumor infiltration significantly and negatively affected OS and PFS in patients with r/r NHL treated with anti-CD19 CAR-T cell therapy. PFS and OS in patients with BM involvement were not significantly different from those of patients with lymph node involvement alone. Thus, anti-CD19 CAR-T cell therapy may improve the prognosis of patients with BM infiltration.

关键词： anti-CD19 chimeric antigen receptor T cell     soft tissue     bone marrow     relapsed or refractory non-Hodgkin lymphoma    

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标题 作者 时间 类型 操作

HLA and lung transplantation

Liya Ju, Caroline Suberbielle, Xiaofan Li, Nuala Mooney, Dominique Charron

期刊论文

DQB1*060101 may contribute to susceptibility to immunoglobulin A nephropathy in southern Han Chinese

null

期刊论文

Advancement of human leukocyte antigen-partially matched related hematopoietic stem cell transplantation

null

期刊论文

immune recovery between event-free patients receiving haploidentical allografts and those receiving humanleukocyte antigen-matched sibling donor allografts

null

期刊论文

嵌合抗原受体和调节性T细胞——移植中人类白细胞抗原特异性免疫抑制的潜力

Sabrina Wright, Conor Hennessy, Joanna Hester, Fadi Issa

期刊论文

HLA 分布仿真扩展研究

吴泽彬,吴慧中,李蔚清

期刊论文

Coronary leukocyte activation in relation to progression of coronary artery disease

null

期刊论文

复杂系统计算机仿真的研究与设计

金士尧,李宏亮,党岗,王召福,刘晓建

期刊论文

Chimeric antigen receptor T cell therapies for acute myeloid leukemia

Bin Gu, Jianhong Chu, Depei Wu

期刊论文

人体前列腺特异性抗原携带含酮基-脱氧壬酮糖酸的N-聚糖

Wei Wang, Tao Zhang, Jan Nouta, Peter A. van Veelen, Noortje de Haan, Theo M. de Reijke, Manfred Wuhrer, Guinevere S.M. Lageveen-Kammeijer

期刊论文

A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma

Houli Zhao, Yiyun Wang, Elaine Tan Su Yin, Kui Zhao, Yongxian Hu, He Huang

期刊论文

Serum carbohydrate antigen (CA) 19-9 as a prognostic factor in cholangiocarcinoma: A meta-analysis

Shang-Long LIU, Zi-Fang SONG, Qing-Gang HU, Shao-Bo HU, Jun LI, Qi-Chang ZHENG, Duo SHAN,

期刊论文

CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a

期刊论文

Detection and monitoring prostate specific antigen using nanotechnology approaches to biosensing

Grant Perry, Fernando Cortezon-Tamarit, Sofia I. Pascu

期刊论文

may affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen

Lili Zhou, Ping Li, Shiguang Ye, Xiaochen Tang, Junbang Wang, Jie Liu, Aibin Liang

期刊论文