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Mechanisms and clinical effects of microchimerism in transfused trauma patients

输血创伤患者微嵌合的机制和临床效果

基本信息

批准号：
7904231
负责人：
MICHAEL Paul BUSCH
金额：
$ 98万
依托单位：
VITALANT
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7904231
关键词：
Acute Lung Injury Address Affect Allogenic Attention Autoimmune Diseases B-Lymphocytes Blood Blood Platelets Blood Transfusion Blood donor Burn Trauma Burn injury CD19 gene CD8B1 gene Cells Characteristics Clinical Clinical Trials Clonal Deletion Clonality Cohort Studies Complication Development Elements Engraftment Epidemiology Future Health Hematopoietic stem cells Immune Tolerance Immune system Immunity Immunologics Immunosuppression Individual Injury Investigation Kinetics Knockout Mice Language Leukocytes Life Liquid substance Lymphocyte Microchimerism Minor Myeloid Cells Operative Surgical Procedures Organ Transplantation Orthopedic Surgery procedures Orthopedics Outcome Patients Physiological Policies Population Pregnancy Prevalence Production Prospective Studies Reaction Regulatory T-Lymphocyte Relative (related person)Reporting Research Research Personnel Resuscitation Risk Safety Soldier Solid Stem cells T-Lymphocyte Testing Therapeutic Time Tissues Transfusion Transplantation Trauma Twin Multiple Birth United States Vascular blood supply anergy arm base blood product chronic autoimmune disease chronic graft versus host disease clinical effect cohort cost follow-up graft vs host disease immunoregulation injured programs research study septic success

项目摘要

DESCRIPTION (provided by applicant): Microchimerism (MC), the stable persistence of cells or tissues from one individual within another, has been described in association with pregnancy, twinning, transplantation, and, most recently, routine blood transfusion. Long-term MC has recently been implicated in the development of a variety of chronic autoimmune diseases. We have reported and confirmed the surprising finding that, in the clinical setting of traumatic injury, leukocytes from a single blood donor can persist in a transfusion recipient for at least three years at a level which rises over time to as much as 3-4% of the recipient's total circulating leukocytes. In our preliminary studies, this transfusion-associated MC (TA-MC) affected 10% of transfused trauma patients long-term and occurred at a similar rate even when all transfused blood products were leukocyte-reduced (LR). Multiple lineages of leukocytes appear to be involved in TA-MC, including B- and T-lymphocytes as well as myelomonocytes. The broad hypothesis behind this proposed research is that TA-MC is a prevalent complication of blood transfusion in patients with severe tissue injury having both adverse and therapeutic implications. To investigate this hypothesis, we propose a set of closely related Specific Aims to determine: 1a) the prevalence of TA-MC in two additional clinical populations in which its occurrence is plausible, burn and orthopedic surgery patients, relative to trauma patients; 1b) the recognizable health problems associated with long-term TA-MC; 2) the kinetics and immunologic mechanisms of TA-MC; and 3) the extent of donor hematopoietic stem cell engraftment and donor lymphocyte clonality in transfusion recipients with long-term high level TA-MC. The epidemiologic aims 1a and 1b will be addressed through a retrospective cohort study (n=600), and the immunologic mechanisms of TA-MC will be investigated in detail in a prospective study of transfused trauma patients (n=360). These studies will identify selected subjects with high-level long-term TA-MC for investigation of engraftment and clonality in aim 3 (n=10). LAY LANGUAGE DESCRIPTION OF THE RESEARCH: From the standpoint of blood use policy, we believe that it is now critical to determine the prevalence of transfusion-associated microchimerism and whether it represents a harmful consequence of transfusion. TA-MC also offers an opportunity to better understand, and potentially exploit, injury-induced tolerance for future therapeutic purposes.

描述（由申请人提供）：微嵌合体（MC），即来自一个个体的细胞或组织在另一个个体中的稳定持久存在，已被描述为与妊娠、孪生、移植以及最近的常规输血相关。长期MC最近被牵连在各种慢性自身免疫性疾病的发展。我们已经报道并证实了一个令人惊讶的发现，即在创伤性损伤的临床环境中，来自单个献血者的白细胞可以在输血接受者体内持续至少三年，其水平随时间上升至接受者总循环白细胞的3-4%。在我们的初步研究中，这种输血相关MC（TA-MC）长期影响10%的输血创伤患者，即使所有输注的血液制品都是白细胞减少（LR）的，发生率也相似。TA-MC中似乎涉及多种白细胞谱系，包括B-和T-淋巴细胞以及骨髓单核细胞。这项拟议研究背后的广泛假设是，TA-MC是严重组织损伤患者输血的常见并发症，具有不良和治疗意义。为了研究这一假说，我们提出了一组密切相关的特定目标，以确定：1a）TA-MC在两个额外的临床人群中的患病率，其中TA-MC的发生是合理的，相对于创伤患者，烧伤和骨科手术患者; 1b）与长期TA-MC相关的可识别的健康问题; 2）TA-MC的动力学和免疫学机制;（3）长期高水平TA-MC输血受者的供者造血干细胞植入程度和供者淋巴细胞克隆性。流行病学目标1a和1b将通过回顾性队列研究（n=600）进行讨论，TA-MC的免疫学机制将在输血创伤患者（n=360）的前瞻性研究中进行详细研究。这些研究将确定选定的高水平长期TA-MC受试者，以研究目标3中的植入和克隆性（n=10）。从血液使用政策的角度来看，我们认为现在关键是要确定输血相关微嵌合体的患病率，以及它是否代表输血的有害后果。TA-MC还提供了一个机会，以更好地了解，并可能利用，损伤诱导的耐受性，为未来的治疗目的。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Immunomodulation in transfused trauma patients.

输血创伤患者的免疫调节。

DOI：
10.1097/aco.0b013e32835d7160
发表时间：
2013
期刊：
Current opinion in anaesthesiology
影响因子：
0
作者：
Jackman,RachaelP
通讯作者：
Jackman,RachaelP

Microchimerism in the transfused obstetric population.

输血产科人群中的微嵌合现象。

DOI：
10.1111/vox.12177
发表时间：
2014
期刊：
Vox sanguinis
影响因子：
2.7
作者：
Bloch,EM;Busch,MP;Lee,T-H;Montalvo,L;Matthews,Y;Bird,A;Bruhn,R;Stefan,V
通讯作者：
Stefan,V

The importance of Foxp3 antibody and fixation/permeabilization buffer combinations in identifying CD4+CD25+Foxp3+ regulatory T cells.

DOI：
10.1002/cyto.a.20815
发表时间：
2009-12
期刊：
CYTOMETRY PART A
影响因子：
3.7
作者：
Law, Jacqueline P.;Hirschkorn, Dale F.;Owen, Rachel E.;Biswas, Hope H.;Norris, Philip J.;Lanteri, Marion C.
通讯作者：
Lanteri, Marion C.

Understanding loss of donor white blood cell immunogenicity after pathogen reduction: mechanisms of action in ultraviolet illumination and riboflavin treatment.