Transfusion-Associated Microchimerism: A New Complication of Blood Transfusions in Severely Injured Patients
Section snippets
Traumatic Injury, Blood Utilization, and TA-MC as a New Complication of Transfusion
In contrast to the situation with traumatic injury, patients receiving transfusion for other conditions such as human immunodeficiency virus (HIV) infection,6 hemoglobinopathies,7 and pediatric structural heart disease (our unpublished data) have shown no evidence of long-term chimerism post-transfusion. Therefore, most current studies of TA-MC focus on severely injured patients receiving relatively fresh blood products.
Blood transfusion is an integral component of life-saving fluid
Early Studies of Transfusion-Associated Microchimerism
Studies from the era before the advent of polymerase chain reaction (PCR) began to examine the clearance of donor leukocytes following blood transfusion. To a limited extent, these studies also addressed donor leukocyte function and interaction with recipient immune cells. During the 1960s, Mohr et al15 observed that tuberculin sensitivity could be transferred from a sensitive donor to a naive recipient through transfusion, leading some investigators to speculate on the existence of a “transfer
Development and Refinement of Gene Amplification Assays for Characterization of Microchimerism
Detection of microchimerism requires highly specialized assays to detect and characterize minor populations of donor cells and the technical aspects of assay development and validation are of pivotal importance to the field. Thus, despite limited but compelling historical observations of TA-MC, detailed investigation had to await the era of gene amplification. Although PCR and other gene amplification strategies have extraordinary sensitivity derived from their ability to amplify a specific
Traumatic Injury and Immunosuppression
An immune deficit, manifested both clinically and in the laboratory, has been recognized in severely injured patients for decades. Based on recent data, it appears likely that this immune deficit may be a necessary but not sufficient precursor for the establishment of TA-MC.
Severe trauma induces short-term immunosuppression, and infectious complications related to immune suppression are an important cause of death in trauma patients.36, 37 Early studies revealed impaired function of the
Recent Clinical Study of Transfusion-Associated Microchimerism in Trauma Patients
Building on these findings, our group has now documented high-level and long-lasting leukocyte microchimerism among a substantial proportion of traumatic injury patients who received a large number of fresh units of blood during their resuscitation.62 In our early studies of TA-MC, we observed that, unlike the short-lived and low levels of chimeric cells found after transfusions in patients having elective surgery, in trauma patients 3% to 4% of peripheral blood leukocytes were of donor origin,
Future Research Directions in Transfusion-Associated Microchimerism
At present, important research questions include (1) whether TA-MC can be observed using combined HLA and InDel strategies in other clinical populations, especially other injured populations (including burn victims, and military personnel receiving a disproportionate amount of very fresh blood); (2) whether patients with TA-MC have consequent adverse health effects, such as acute or chronic graft-versus-host disease or so-called autoimmune disease syndromes or laboratory manifestations of
Summary and Conclusions
Microchimerism has been recently described in association with a number of specific allogeneic exposures, including pregnancy, transplantation, and blood transfusion. The phenomenon of TA-MC in patients transfused for severe traumatic injury has now been well documented. Our findings show that in the immunomodulatory milieu of severe traumatic injury, transfused leukocytes, typically from a single blood donor, are able to persist for months to years at a level that rises over time to as much as
References (66)
Microchimerism: Incidental byproduct of pregnancy or active participant in human health?
Trends Mol Med
(2002)- et al.
Survival of transfused donor white blood cells in HIV-infected recipients
Blood
(2001) Current concepts of the inflammatory response after major trauma: An update
Injury
(2003)- et al.
Circulation of donor lymphocytes after blood transfusion in man
Blood
(1977) - et al.
Persistence of donor cells in neonates after fetal and exchange transfusion
Am J Obstet Gynecol
(1971) - et al.
Detection of circulating donor white blood cells in patients receiving multiple transfusions
Blood
(1992) - et al.
Transient increase in circulating donor leukocytes after allogeneic transfusion in immunocompetent recipients compatible with donor cell proliferation
Blood
(1995) - et al.
Measuring infectious bursal disease virus RNA in blood by multiplex real-time quantitative RT-PCR
J Virol Methods
(2000) - et al.
Multiplex detection of single-nucleotide variations using molecular beacons
Genet Anal
(1999) - et al.
Quantitative real-time PCR using TaqMan and SYBR Green for Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, tetQ gene and total bacteria
FEMS Immunol Med Microbiol
(2003)
Quantitative reverse transcription-polymerase chain reaction to study mRNA decay: Comparison of endpoint and real-time methods
Anal Biochem
Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction
Blood
Induction of tolerance in nondefective mice after in utero transplantation of major histocompatibility complex-mismatched fetal hematopoietic stem cells
Blood
The role of interleukin 6 in interferon-gamma production in thermally injured mice
Cytokine
Survival of donor leukocyte subpopulations in immunocompetent transfusion recipients: Frequent long-term microchimerism in severe trauma patients
Blood
Microchimerism: An investigative frontier in autoimmunity and transplantation
JAMA
Microchimerism in human health and disease
Autoimmunity
Pregnancy and microchimerism in autoimmune disease: protector or insurgent?
Arthritis Rheum
Microchimerism and human autoimmune diseases
Lupus
Sample suitability for the detection of minor white cell populations (microchimerism) by polymerase chain reaction
Transfusion
Blood transfusion rates in the care of acute trauma
Transfusion
Optimizing the use of blood products in trauma care
Crit Care
Comprehensive Report on Blood Collection and Transfusion in the United States in 2001
Blood use in war and disaster: Lessons from the past century
Transfusion
Both T-helper-1- and T-helper-2-type lymphokines are depressed in posttrauma anergy
J Trauma
Current and emerging infectious risks of blood transfusions
JAMA
Transfer of delayed hypersensitivity: the role of blood transfusions in humans
JAMA
Lymphocyte response to blood transfusion in man
N Engl J Med
Chimerism following fetal transfusionReport of leucocyte hybridization and infant with acute lymphocytic leukaemia
Scand J Haematol
The power of primers (editorial)
Transfusion
Detection of microchimerism by PCR is a function of amplification strategy
Transfusion
Comparison of real-time PCR with SYBR Green I or 5′-nuclease assays and dot-blot hybridization with rDNA-targeted oligonucleotide probes in quantification of selected faecal bacteria
Microbiology
Enhanced ascertainment of microchimerism using real-time quantitative PCR amplification of insertion/deletion polymorphisms
Transfusion
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Supported in part by grant R01-HL-083388 and a Specialized Center of Research (SCOR) grant in Transfusion Medicine from the National Heart Lung and Blood Institute (P50-HL-54476), and in part by a grant from the Blood Systems Foundation, Scottsdale, AZ.