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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL083388-03
Application #
7479573
Study Section
Special Emphasis Panel (ZRG1-HEME-B (01))
Program Officer
Welniak, Lisbeth A
Project Start
2006-09-01
Project End
2011-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
3
Fiscal Year
2008
Total Cost
$1,235,637
Indirect Cost
Name
Blood Systems Research Institute
Department
Type
DUNS #
006902498
City
San Francisco
State
CA
Country
United States
Zip Code
94118
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Bloch, Evan M; Jackman, Rachael P; Lee, Tzong-Hae et al. (2013) Transfusion-associated microchimerism: the hybrid within. Transfus Med Rev 27:10-20
Jackman, Rachael P (2013) Immunomodulation in transfused trauma patients. Curr Opin Anaesthesiol 26:196-203
Sanchez, Rosa; Lee, Tzong-Hae; Wen, Li et al. (2012) Absence of transfusion-associated microchimerism in pediatric and adult recipients of leukoreduced and gamma-irradiated blood components. Transfusion 52:936-45
Jackman, Rachael P; Utter, Garth H; Muench, Marcus O et al. (2012) Distinct roles of trauma and transfusion in induction of immune modulation after injury. Transfusion 52:2533-50
Suskind, David L; Kong, Denice; Stevens, Anne et al. (2011) Maternal microchimerism in pediatric inflammatory bowel disease. Chimerism 2:50-4
Jackman, Rachael P; Utter, Garth H; Heitman, John W et al. (2011) Effects of blood sample age at time of separation on measured cytokine concentrations in human plasma. Clin Vaccine Immunol 18:318-26
Bloch, Evan M; Reed, William F; Lee, Tzong-Hae et al. (2011) Male microchimerism in peripheral blood leukocytes from women with multiple sclerosis. Chimerism 2:6-10
Lee, Tzong-Hae; Chafets, Daniel M; Biggar, Robert J et al. (2010) The role of transplacental microtransfusions of maternal lymphocytes in in utero HIV transmission. J Acquir Immune Defic Syndr 55:143-7

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