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Blood, Vol. 93 No. 6 (March 15), 1999:
pp. 2033-2037
Long-Term Fetal Microchimerism in Peripheral Blood Mononuclear Cell
Subsets in Healthy Women and Women With Scleroderma
Paul C. Evans,
Nathalie Lambert,
Sean Maloney,
Dan E. Furst,
James
M. Moore, and
J. Lee Nelson
From the Fred Hutchinson Cancer Research Center, Seattle, WA.
Fetal CD34+ CD38+ cells have recently
been found to persist in maternal peripheral blood for many years after
pregnancy. CD34+ CD38+ cells are progenitor
cells that can differentiate into mature immune-competent cells. We
asked whether long-term fetal microchimerism occurs in T lymphocyte, B
lymphocyte, monocyte, and natural-killer cell populations of previously
pregnant women. We targeted women with sons and used polymerase chain
reaction for a Y-chromosome-specific sequence to test DNA extracted
from peripheral blood mononuclear cells (PBMC) and from CD3, CD19,
CD14, and CD56/16 sorted subsets. We also asked whether persistent
microchimerism might contribute to subsequent autoimmune disease in the
mother and included women with the autoimmune disease scleroderma.
Scleroderma has a peak incidence in women after childbearing years and
has clinical similarities to chronic graft-versus-host disease that
occurs after allogeneic hematopoietic stem-cell transplantation, known
to involve chimerism. Sixty-eight parous women were studied for male
DNA in PBMC and 20 for PBMC subsets. Microchimerism was found in PBMC
from 33% (16 of 48) of healthy women and 60% (12 of 20) women with
scleroderma, P = .046. Microchimerism was found in some women
in CD3, CD19, CD14, and CD56/16 subsets including up to 38 years after
pregnancy. Microchimerism in PBMC subsets was not appreciably more
frequent in scleroderma patients than in healthy controls. Overall,
microchimerism was found in CD3, CD19, and CD14 subsets in
approximately one third of women and in CD56/16 in one half of women.
HLA typing of mothers and sons indicated that HLA compatibility was not
a requirement for persistent microchimerism in PBMC subsets. Fetal microchimerism in the face of HLA disparity implies that specific maternal immunoregulatory pathways exist that permit persistence but
prevent effector function of these cells in normal women. Although
microchimerism in PBMC was more frequent in women with scleroderma than
healthy controls additional studies will be necessary to determine
whether microchimerism plays a role in the pathogenesis of this or
other autoimmune diseases.
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