Naturally acquired microchimerism: implications for transplantation outcome and novel methodologies for detection.
Microchimerism represents a condition where one individual harbors genetically distinct cell populations, and the chimeric population constitutes <1% of the total number of cells. The most common natural source of microchimerism is pregnancy. The reciprocal cell exchange between a mother and her child often leads to the stable engraftment of hematopoietic and non-hematopoietic stem cells in both parties. Interaction between cells from the mother and those from the child may result in maternal immune cells becoming sensitized to inherited paternal alloantigens of the child, which are not expressed by the mother herself. Vice versa, immune cells of the child may become sensitized toward the non-inherited maternal alloantigens of the mother. The extent of microchimerism, its anatomical location, and the sensitivity of the techniques used for detecting its presence collectively determine whether microchimerism can be detected in an individual. In this review, we focus on the clinical consequences of microchimerism in solid organ and hematopoietic stem cell transplantation, and propose concepts derived from data of epidemiologic studies. Next, we elaborate on the latest molecular methodology, including digital PCR, for determining in a reliable and sensitive way the extent of microchimerism. For the first time, tools have become available to isolate viable chimeric cells from a host background, so that the challenges of establishing the biologic mechanisms and function of these cells may finally be tackled.
Department of Immunohematology and Blood Transfusion; Leiden University Medical Center; Leiden, the Netherlands.
Michael
M
Eikmans
Immunology Laboratory; Willem Alexander Children's Hospital; Leiden University Medical Center; Leiden, the Netherlands.
Astrid G S
AG
van Halteren
Weil Cornell Medical College; New York City, NY USA.
Koen
K
van Besien
Department of Immunohematology and Blood Transfusion; Leiden University Medical Center; Leiden, the Netherlands; Europdonor Foundation; Leiden, the Netherlands.
Jon J
JJ
van Rood
Department of Immunohematology and Blood Transfusion; Leiden University Medical Center; Leiden, the Netherlands.
Jos J M
JJ
Drabbels
Department of Immunohematology and Blood Transfusion; Leiden University Medical Center; Leiden, the Netherlands.
Frans H J
FH
Claas
D000818:Animals; D046528:Chimerism; D005312:Fetal Blood / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007108:Immune Tolerance; D016377:Organ Transplantation; D016133:Polymerase Chain Reaction / Q000379:methods; D059010:Single-Cell Analysis / Q000379:methods; D019737:Transplants / Q000276:immunology*
FACS sorting; digital PCR; graft-versus-host disease; maternal antigen; microchimerism; mixed chimerism; monoclonal antibodies; paternal antigen; pregnancy; qPCR; single cell analysis; transplantation