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

• 批准号: 7148523
• 负责人: MICHAEL Paul BUSCH
• 金额: $ 102.82万
• 依托单位: VITALANT
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7148523
• 关键词: autoimmune disorder; blood transfusion; burns; cell population study; clinical research; clone cells; epidemiology; graft versus host disease; hematopoietic stem cells; human subject; leukocytes; longitudinal human study; lymphocyte; medical complication; orthopedics; tissue mosaicism; transplantation immunology; trauma

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）：已经描述了微chimerismist（MC），一种与妊娠，孪生，移植以及最近的常规输血有关的细胞或组织的稳定持续性。长期MC最近与多种慢性自身免疫性疾病的发展有关。我们已经报告并证实了令人惊讶的发现，在创伤性损伤的临床环境中，来自单个献血者的白细胞至少可以在输血接受者中持续至少三年，而随着时间的推移，该水平可以持续到3-4％的总循环白细胞。在我们的初步研究中，这种输血相关的MC（TA-MC）长期影响了10％的输血性创伤患者，即使所有输血的血液产物都是白细胞还原（LR），也以类似的速度发生。白细胞的多个谱系似乎参与了TA-MC，包括B-和T淋巴细胞以及脊髓细胞。这项拟议的研究背后的广泛假设是，TA-MC是具有不良和治疗意义的严重组织损伤患者的血液输血的普遍并发症。为了研究这一假设，我们提出了一组密切相关的特定目的，以确定：1a）在另外两个临床人群中，其发生合理的临床人群的患病率相对于创伤患者，其发生的情况是合理的，烧伤和骨科手术患者； 1b）与长期TA-MC相关的可识别健康问题； 2）TA-MC的动力学和免疫机制； 3）供体造血干细胞植入和供体淋巴细胞克隆性的供体长期TA-MC的供体淋巴细胞克隆性的程度。流行病学目的1a和1b将通过回顾性队列研究（n = 600）来解决，TA-MC的免疫机制将在一项针对输血创伤患者的前瞻性研究中进行详细研究（n = 360）。这些研究将确定具有高级长期TA-MC的选定受试者，以研究AIM 3（n = 10）中的植入和克隆性。研究的外行语言描述：从血液使用政策的角度来看，我们认为现在确定与输血相关的微思维主义的普遍性以及它是否代表输血的有害后果至关重要。 TA-MC还提供了一个机会，可以更好地理解和可能利用伤害引起的耐受性来实现未来的治疗目的。