- Michael Verneris
Author
Affiliations
Fetal microchimerism (FMc)
describes the persistence of low numbers of fetal cells in the mother after a
pregnancy. A number of recent studies suggests FMc may play a role in the
etiology of some autoimmune diseases.1 Remarkably, FMc has been
demonstrated to persist for up to 38 years after pregnancy and has been found in
multiple lymphocyte subsets and in early lymphoid precursors.2 In a single
patient, FMc was demonstrated in CD34+ cells, suggesting that FMc may
result from the engraftment of a long-term repopulating or stem cell.3 In this issue of
Blood, Adams and colleagues (page 3845) have taken the next step and
evaluated female hematopoietic cell (HC) transplant donors for the presence of Y
chromosome-specific DNA. Strikingly, Y chromosome DNA could be detected in more
than one third of peripheral blood stem cell (PBSC) collections and nearly one
half of the CD34+ selected cell fractions from these female donors.
Since the use of multiparous female donors is associated with a higher
propensity of graft-versus-host disease (GVHD),4 the authors speculate that major
histocompatibility complex (MHC)-mismatched fetal cells transferred during HC
transplantation (HCT) could participate in the induction of GVHD. Unfortunately,
a number of factors are lacking from this dataset to completely address such
questions. For instance, parity information is not available for most donors,
and the assay used detects only male DNA; thus, the actual incidence of FMc in
hematopoietic stem cell factions may be significantly higher than is estimated
by this analysis. Likewise, it is not known whether female donors with
demonstrable FMc induced a greater incidence of GVHD than other donors in this
series.⇓
Despite this, and like all good science, this work raises more
questions than it answers. For instance, virtually nothing is known about the
circumstances that allow FMc to occur. Other important questions include what
role do such cells play in the pathogenesis of either acute or chronic GVHD. If
the hypothesis by Adams et al is correct, then it may be possible to detect the
presence of transferred fetal cells in the host after HCT (possibly in GVHD
target tissues). To date there have been no reports of chimerism analysis after
HCT demonstrating a party other than the donor or recipient, but the studies by
Adams et al may prompt such reports.
Not only have fetal cells been detected in the mother, but also
maternal cells in the fetus.5 Such microchimerism might not be all
bad for patients requiring HCT, since it might aid, or even enhance, donor
selection. This is because a potential sibling donor (with maternal
microchimerism) may be tolerant of noninherited maternal antigens, allowing for
less rigorous typing of maternal alleles. Similarly, mothers who have had
multiple pregnancies (and hence FMc from more than one child) may be tolerant of
paternal antigens. Such parents may be ideal donors for their children. In fact,
Shimazaki et al have reported a technique of donor selection based on
microchimerism analysis to perform haploidentical, 2 to 3 antigen mismatched,
non-T-cell-depleted HCT.6 In this series of 5 patients the
incidence of severe (grades 3-4) GVHD was remarkably low (1 of 5 patients).
Thus, it is hopeful that the findings by Adams et al may be useful in the
understanding of FMc and how (or if) it relates to the pathogenesis of GVHD and
whether such information may assist in the selection of HC transplant
donors.
- Copyright © 2003 by The American Society of Hematology
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