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 Previous Article | Table of Contents | Next Article 
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
By
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.
 |
ABSTRACT |
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.
© 1999 by The American Society of Hematology.
| |
INTRODUCTION |
BIDIRECTIONAL TRAFFIC of cells at the
fetal-maternal interface has been shown during pregnancy.1
Moreover, fetal progenitor cells have been found to persist in maternal
peripheral blood for decades after childbirth.2 Progenitor
cells can differentiate into mature immune-competent cells. We
therefore asked whether persistent fetal microchimerism also occurs in
peripheral blood mononuclear cell (PBMC) subpopulations including T and
B lymphocytes, monocytes, and natural-killer (NK) cells. As discussed
by Lo et al,1 maternal-fetal cell trafficking has important
biological ramifications in the context of hematopoietic stem cell
transplantation, vertical transmission of infectious agents, and
maternal tolerance of the fetus during pregnancy. Persistent fetal
microchimerism also has potential implications for some autoimmune
diseases. Scleroderma (systemic sclerosis; SSc) is an
autoimmune disease with a strong predilection for women, a peak
incidence in women after childbearing years,3 and clinical
similarities to chronic graft-versus-host disease (cGVHD).4
We therefore also studied women with this disease. In this paper we
report evidence for fetal microchimerism in PBMC and PBMC
subpopulations of previously pregnant healthy women and women with
scleroderma. Women with sons were recruited and Y chromosome DNA and
fetal-specific HLA DNA were used as markers of persistent fetal-cell microchimerism.
| |
MATERIALS AND METHODS |
Subjects.
Clinical specimens were collected from 48 healthy women with sons
including 13 sisters of women with SSc. The mean age was 43.1 years (34 to 71). The mean number of children was 2.2 (1 to 7) with mean number
of sons 1.7 (1 to 6). The mean age at birth of the first child was 27.5 years (15 to 39), mean age at birth of first son was 28.1 years (15 to
39), mean age at birth of last child was 30.3 years (15 to 39), and
mean age at birth of last son was 29.5 (15 to 39). The mean age of the
last child to be born was 12.8 years (0 to 45) and mean age of the last
son to be born was 15.1 (0 to 45).
Twenty women with SSc with sons were studied with the mean age of 48.8 years (34 to 71). The mean number of children was 3.8 (1 to 7) with
mean number of sons 1.8 (1 to 4). The mean age at birth of the first
child was 24.1 years (17 to 36), mean age at birth of first son was
24.8 years (18 to 36), mean age at birth of last child was 28 years (23 to 36), and mean age at birth of last son was 27.3 years (20 to 36).
The mean age of the last child to be born was 19.6 years (1 to 40) and
the mean age of the last son to be born was 21.1 years (1 to 42). The
mean age at diagnosis of SSc was 44.1 years (29 to 62) and the mean
time between birth of first child and diagnosis of SSc was 17.3 years
(2 to 42). Specimens were also collected from 2 nulligravid women and
22 parous women who had not given birth to a son.
DNA extraction from peripheral blood mononuclear cells (PBMC).
A total of 30 mL acid-citrate-dextrose (ACD)-preserved peripheral
blood was purified by ficoll hypaque density centrifugation. DNA was
extracted from PBMC using the Isoquick Nucleic Acid Extraction Kit
(Orca Research Inc, Bothell, WA) in accordance with the
manufacturer's instructions.
DNA extraction from fluorescent-activated cell sorted (FACS) PBMC
subsets.
PBMC were purified from ACD-preserved blood as described above and
resuspended in phosphate-buffered saline (PBS)/1% fetal calf serum
(FCS). Ten to 20 × 106 cells were aliquotted into
three tubes and stained with anti-CD3 fluorescein isothiocyanate (FITC)
and anti-CD56/16 PE (tube 1), anti-CD14 FITC and anti-CD19 PE (tube 2),
and anti-CD34 PE and anti-CD14 FITC (tube 3). Four µL of each
fluorescently conjugated antibody (Becton Dickinson, Mountain View,
CA) was used for staining a total volume of 500 µL.
Tubes were incubated on ice in the dark for 30 minutes then washed
twice with 5 mL PBS/1% FCS before FACS sorting. Cells were sorted into
CD3+, CD56/16+, CD14+, and
CD19+ populations. A proportion of sorted cells was then
examined by FACS to check purity, which was always 95% to 99%. Cells
were then collected by centrifugation and stored above liquid nitrogen. DNA was extracted using the Isoquick Nucleic Acid Extraction Kit (Orca
Research Inc) and Y-chromosome-specific PCR was performed. DNA was
routinely extracted from 0.5 × 105 cells although
occasionally smaller or greater numbers were studied.
Detection of fetal microchimerism by PCR for Y-chromosome-specific
DNA.
Nested PCR for a single-copy Y-chromosome-specific sequence was
modified from Lo et al5; reagents were supplied by Perkin Elmer unless otherwise stated. Measures were taken to prevent contamination including dedicated rooms, equipment, and reagents for
PCR reaction mix and product analysis and use of three laminar flow
hoods for DNA extraction, reaction mix preparation, and transfer of
primary products after step 1. For step 1 each reaction tube contained
1 µg template DNA, 50 pmol sense primer (5-CTAGACCGCAGAGGCGCCAT-3; Oligos Etc) and 50 pmol antisense primer (5-TAGTACCCACGCCTGCTCCGG-3; Oligos Etc), 200 µM dNTPs, 1.5mmol/L MgCl2, 1 × Taq
polymerase buffer, 1 µL Perfect Match Enhancer (Stratagene, La Jolla,
CA), and 1µL Amplitaq gold. Forty cycles were performed
(94°C for 1 minute, 67°C for 1 minute, 72°C for 2 minutes).
For step 2 each reaction tube contained 2 µL reaction product from
step 1 DNA, 50 pmol sense primer (5-CATCCAGAGCGTCCCTGGCTT-3; Oligos
Etc) and 50 pmol antisense primer (5-CTTTCCACAGCCACATTTGTC-3; Oligos
Etc), 200µmol/L dNTPs, 1.5 mmol/L MgCl2, 1 × Taq
polymerase buffer, 1 µL Perfect Match Enhancer (Stratagene) and 1µL
Amplitaq gold. Twenty five cycles were performed (94°C
for 1 minute, 55°C for 1 minute, 72°C for 2 minutes). Positive
(male DNA) and negative (water) controls were included in each run. A
total of 5 µL PCR product was electrophoresed in a 2% agarose gel
(Sigma Chemical Co, St Louis, MO) using TAE buffer (0.04 mol/L Tris-acetate, 0.001 mol/L EDTA). Gels were photographed over
ultraviolet light after staining with ethidium bromide. Serial
dilutions showed that the DNA equivalent of one male cell could be
detected in a background of 4 × 105 female cells. No
amplification was observed from negative water controls or from DNA
extracted from nulligravid women. Southern blotting was performed onto
nylon membrane (Boehringer Mannheim, Mannheim, Germany)
following the manufacturer's instructions to confirm specificity. A
PCR product-specific oligonucleotide
(5'-CAGCTCGGCTTCGATGTGACTCTT-3') was end labelled with
 -ATP (Amersham, Arlington Heights, IL) and used to
hybridize against blotted PCR product to confirm specificity.
Detection of fetal microchimerism by PCR for HLA-specific sequences.
The presence of fetal microchimerism was substantiated further in some
patients using HLA-specific PCR. PCR reactions were performed in a
volume of 50 µL containing 1.5 µg genomic DNA, 10 mmol/L Tris-HCl
(pH 8.3), 50 mmol/L KCl, 1.5 mmol/L MgCl2, 0.001% wt/vol
gelatin, 260 µmol/L of each deoxynucleotide, 0.5 U Perfect Match
Enhancer (Stratagene), 2.5 U Amplitaq Gold DNA Polymerase (Perkin
Elmer-Cetus, Norwalk, CT) and 20 pmol of each of the
HLA-specific primers. Amplification consisted of 5 minutes at 96°C
followed by 35 cycles at 95°C for 35 seconds, 55 to 65°C for 35 seconds and 72°C for 1 minute with a final extension step at
72°C for 10 minutes using a Gene Amp System 9600 (Perkin
Elmer-Cetus). Optimum amplification sensitivity and specificity was
achieved for each primer set by titrating MgCl2 and primer
concentrations and optimizing annealing temperature and number of
thermocycles. To control for nonspecific amplification of background
HLA alleles, DNA was extracted from control PBMC or from Epstein-Barr
virus (EBV)-transformed human B-lymphoblastoid cell lines expressing HLA alleles of the mother (and not the child). Negative controls comprising all PCR reagents without DNA were also included. DNA from
the subject's child served as a positive control for HLA-specific PCR.
Statistical analysis.
Calculations of statistical significance were done using the
Mantel-Haenszel test of the null hypothesis that the odds ratio is
equal to one (StatXact program).
| |
RESULTS |
Fetal microchimerism in PBMC of healthy women and women with
scleroderma with sons.
Thirty-one percent (11 of 35) of normal healthy women had Y chromosome
DNA in PBMC. Patients with SSc were more frequently positive for Y
chromosome DNA in PBMC than healthy women; 60% of SSc patients were
positive, P = .042 (Table 1). The
frequency of Y chromosome PCR-positive PBMC was not significantly
different amongst sisters of women with SSc and healthy women. Patients with SSc were more frequently positive for Y chromosome DNA in PBMC
than the combined control population of healthy women and sisters of
women with SSc; 60% of SSc patients were positive compared with 33%
controls, P = .046.
In control experiments we found that two nulligravid women were
consistently negative for Y-chromosome-specific DNA. However, 10 of 22 parous women who had never given birth to a male were positive (5 patients and 5 controls). Eight of the 10 had prior pregnancy loss
and/or transfusions that represent a potential source of Y
chromosome DNA in these subjects.
The presence of DNA from a son as detected by
Y-chromosome-specific DNA PCR was confirmed in some families
by use of HLA-specific PCR. In these families HLA differences of the
son were exploited to study DNA extracted from PBMC of the patient. In
one family DRB1*01-specific primers were used, in two families
DRB5-specific primers, and in another family B44 (HLA class I)-specific
primers were used.
Fetal microchimerism in PBMC subsets of healthy women and women with
scleroderma.
PCR for Y chromosome DNA was performed on FACS sorted subsets for 20 women. Eleven controls comprised 9 normal healthy women and 2 healthy
sisters of women with SSc. All subjects were positive for Y chromosome
DNA in unsorted PBMC. Table 2 shows that
Y-chromosome-positive cells were frequently detected in PBMC subsets
for both controls and patients. Three of 10 (30%) controls and 3 of 9 (33%) scleroderma patients were positive in CD3+ cells. In
CD56/CD16+ cells 4 of 9 (44%) and 5 of 8 (63%) were
positive. In CD14+ cells 4 of 11 (36%) and 2 of 9 (22%)
were positive. In CD19+ cells 5 of 11 (45%) and 2 of 8 (25%) were positive respectively. Two patients had not given birth to
a male child, however, patient SSc4 had two prior pregnancy losses and
received transfusions at the time of childbirth and patient SSc33 had
prior pregnancy loss.
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Table 2.
Persistent Microchimerism in Peripheral Blood
Mononuclear cell Subsets in Healthy Women and Women With
Scleroderma
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Table 3.
HLA-Compatibility of a Previously Born son and
Persistent Microchimerism in Peripheral Blood Mononuclear cell
Subsets
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HLA compatibility and microchimerism in PBMC subsets.
Family HLA studies were completed for 17 women (sons of 1 woman were
not available and 2 did not have a son as noted above). Sons were HLA
class-II incompatible with their mothers for DRB1, DQA1, and DQB1 in
the majority of families (53%). Nevertheless, persistent
microchimerism was found in PBMC subsets in all of these women (Table
3). Persistent microchimerism was detected in each of the subsets, CD3,
CD56/16, CD14, and CD19 in some women. No significant difference was
apparent for 8 women with a son who was compatible for 1 or more of the
class-II loci, DRB1, DQA1, and/or DQB1. Again, persistent
microchimerism was detected in some women in each of the subsets, CD3,
CD56/16, CD14, and CD19.
| |
DISCUSSION |
Application of molecular biological techniques to the study of human
pregnancy has resulted in the appreciation that there is bidirectional
traffic of cells between mother and child.1 Moreover, fetal
progenitor cells have been found to persist in the maternal peripheral
blood for decades after pregnancy.2 Because progenitor
cells can differentiate into other immune-competent cells populations,
we asked whether persistent microchimerism occurs in PBMC
subpopulations. Y chromosome DNA served as a marker for persistent male
fetal cells in women who had previously given birth to a son. Healthy
women frequently had male DNA in their PBMC despite a mean age of the
last son to be born of 15 years.
Long-term persistence of fetal cells has potential biological
significance,1 including the possibility that these cells could be involved in some autoimmune diseases.6 We studied women with SSc because of the hypothesized link between microchimerism and development of this autoimmune disease.6 SSc is a
progressive and often fatal connective tissue disease characterized by
inflammation, fibrosis, and obliterative vasculopathy of skin, lung,
heart, kidney, and gut.7 SSc shares a number of
characteristics with cGVHD that may arise after hematopoietic stem-cell
transplantation,4 has a higher incidence among women than
men, and rises sharply following childbearing years.3 A
significantly greater proportion of women with SSc had male DNA in PBMC
compared with control women with sons. The mean age since last birth of
a son in SSc patients was 21 years. The nested PCR test employed was
not quantitative, but the difference between healthy women and women
with SSc could reflect a quantitative difference because negative
subjects may harbor fetal cells at a level below the sensitivity of the
test. This is consistent with our previous report of a smaller series that was limited to testing of whole blood samples in which
it was shown that women with SSc compared with controls
harbor a greater quantity of DNA of fetal origin in peripheral
blood.8
In PBMC subpopulations we found persistent microchimerism in the
majority of healthy women and also in women with scleroderma. Ninety
percent of women had microchimerism in some PBMC subpopulation, either
in T lymphoctyes, B lymphoctyes, monocytes, and/or in NK cell populations. Only one woman was positive for all subpopulations, and this subject had the most recent delivery of a son. Thus, most
women evidenced persistent microchimerism in some, but not all PBMC
subpopulations. Microchimerism may be detected more readily after
application of FACS because greater concentrations of specific PBMC
subsets can be tested than would be present in whole PBMC. Due to the
relative purity with which PBMC subpopulations can be attained with
FACS it is possible that microchimerism detected could be from a
contaminating-cell subset. The nested PCR was sensitive, capable of
detecting the DNA equivalent of a single cell so that if, for example,
sorting purity was 95% there could be a 1 in 20 chance that
microchimerism detected was not from the subset of interest. Whereas it
is possible that an individual determination could be in error, a
systemic error is unlikely, purity was always greater than 95%, and
most subjects were studied on more than one occasion and with multiple
aliquots of cells. It is therefore unlikely that this consideration
impacts the overall study results.
Long-term microchimerism of fetal cells in the peripheral blood of
parous women is a recent concept.2 Persistence of fetal cells after nonterm pregnancies has not been specifically studied, but
is the most likely explanation for positive results in some women
without a son. Fetal cells have been detected in maternal peripheral
blood as early as 5-weeks gestation.9 In control experiments we found Y chromosome positivity in 10 parous women without
sons, all but two of whom had history of prior pregnancy losses
and/or had received blood transfusions. Another potential source is through transfusion that has, in some cases, led to the
development of GVHD.10,11 A potential source of male
chimeric cells remains unexplained for two women who may have
experienced an unrecognized early pregnancy loss. Although the
possibility of contamination cannot be entirely ruled out, stringent
measures were employed to minimize this risk and negative controls were consistently negative. A final potential source of microchimerism is
engraftment of cells from a twin that could occur early in pregnancy
with later unrecognized loss of the twin. Chimeric cells were first
described by Owen12 who detected red blood cell antigen sharing between dizygotic twin cattle. Interestingly, one control woman
in the present study, with two daughters and one early pregnancy loss
also had a twin brother, and was consistently positive for Y chromosome DNA.
The factors facilitating microchimerism are poorly understood. It can
be envisaged that patient age and/or time since childbirth could influence fetal-cell microchimerism; however, there was no
readily apparent correlation of these variables with results in our
study. Total parity also did not correlate with microchimerism.
Persistent fetal microchimerism raises the issue of maternal tolerance
to fetal paternally inherited HLA antigens. Maternal T-cell13 and humoral14 awareness of paternally
inherited antigens has been shown during and after pregnancy. In a
murine model it was found that fetal cells are cleared from the
maternal circulation more rapidly after allogeneic matings than
syngeneic.15 In this study there was no apparent
correlation between HLA compatibility of a son and the long-term
persistence of male DNA in PBMC subsets. We found evidence for
persistent microchimerism in CD3+, CD56/CD16+,
CD14+, and CD19+ PBMC subsets in healthy women
and in women with SSc for whom all previously born sons were
HLA-incompatible.
In summary, our findings show that persistent fetal microchimerism
is not uncommon in normal healthy women in T-lymphocyte, B-lymphocyte,
NK, and monocyte-cell populations. Significantly, more women with SSc
had microchimerism in unsorted PBMC than controls, however, additional
studies will be necessary to address the potential role of
microchimerism in the pathogenesis of SSc and other autoimmune diseases.
| |
FOOTNOTES |
Submitted August 24, 1998; accepted November 11, 1998.
Supported by NIH grants AI38583 and AI41721 and the Scleroderma Federation.
The publication costs of this
article were defrayed in part by
page charge payment. This article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. section
1734 solely to indicate this fact.
Address correspondence to J. Lee Nelson, Immunogenetics D2-100, Fred
Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA
98109.
| |
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V. K. Gadi, J. L. Nelson, N. D. Boespflug, K. A. Guthrie, and C. S. Kuhr
Soluble Donor DNA Concentrations in Recipient Serum Correlate with Pancreas-Kidney Rejection
Clin. Chem.,
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[Abstract]
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I. B. Pedersen, P. Laurberg, N. Knudsen, T. Jorgensen, H. Perrild, L. Ovesen, and L. B. Rasmussen
Lack of association between thyroid autoantibodies and parity in a population study argues against microchimerism as a trigger of thyroid autoimmunity
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[Abstract]
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K. Khosrotehrani and D. W. Bianchi
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C. Vernochet, S. M. Caucheteux, M.-C. Gendron, J. Wantyghem, and C. Kanellopoulos-Langevin
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Biol Reprod,
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[Abstract]
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C. Renne, E. Ramos Lopez, S. A. Steimle-Grauer, P. Ziolkowski, M. A. Pani, C. Luther, K. Holzer, A. Encke, R. A. Wahl, W. O. Bechstein, et al.
Thyroid Fetal Male Microchimerisms in Mothers with Thyroid Disorders: Presence of Y-Chromosomal Immunofluorescence in Thyroid-Infiltrating Lymphocytes Is More Prevalent in Hashimoto's Thyroiditis and Graves' Disease Than in Follicular Adenomas
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[Abstract]
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K. Khosrotehrani, K. L. Johnson, D. H. Cha, R. N. Salomon, and D. W. Bianchi
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JAMA,
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[Abstract]
[Full Text]
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E. Hocht-Zeisberg, H. Kahnert, K. Guan, G. Wulf, B. Hemmerlein, T. Schlott, G. Tenderich, R. Korfer, U. Raute-Kreinsen, and G. Hasenfuss
Cellular repopulation of myocardial infarction in patients with sex-mismatched heart transplantation
Eur. Heart J.,
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[Abstract]
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M. Verneris
Fetal microchimerism--what our children leave behind
Blood,
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[Full Text]
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K. M. Adams, N. C. Lambert, S. Heimfeld, T. S. Tylee, J. M. Pang, T. D. Erickson, and J. L. Nelson
Male DNA in female donor apheresis and CD34-enriched products
Blood,
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3845 - 3847.
[Abstract]
[Full Text]
[PDF]
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K. O'Donoghue, M. Choolani, J. Chan, J. de la Fuente, S. Kumar, C. Campagnoli, P.R. Bennett, I.A.G. Roberts, and N.M. Fisk
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[Abstract]
[Full Text]
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M Mosca, M Curcio, S Lapi, G Valentini, S D'Angelo, G Rizzo, and S Bombardieri
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[Abstract]
[Full Text]
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R. Poulsom, M. R. Alison, T. Cook, R. Jeffery, E. Ryan, S. J. Forbes, T. Hunt, S. Wyles, and N. A. Wright
Bone Marrow Stem Cells Contribute to Healing of the Kidney
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[Abstract]
[Full Text]
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C. Shimazaki, N. Ochiai, R. Uchida, A. Okano, S.-i. Fuchida, E. Ashihara, T. Inaba, N. Fujita, E. Maruya, and M. Nakagawa
Non-T-cell-depleted HLA haploidentical stem cell transplantation in advanced hematologic malignancies based on the feto-maternal michrochimerism
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[Abstract]
[Full Text]
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L. A. Cox, R. C. Ramos, T. N. Dennis, S. A. Jimenez, J. B. Smith, and C. M. Artlett
Detection of Microchimeric Cells in the Peripheral Blood of Nonpregnant Women Is Enhanced by Magnetic Cell Sorting before PCR
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A Selva-O'Callaghan, T Mijares-Boeckh-Behrens, E B. Prades, R Solans-Laque, C P Simeon-Aznar, V Fonollosa-Pla, and M Vilardell-Tarres
Lack of evidence of foetal microchimerism in female Spanish patients with systemic sclerosis
Lupus,
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[Abstract]
[PDF]
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J R Scott
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Lupus,
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[Abstract]
[PDF]
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N. C. Lambert, Y. M. D. Lo, T. D. Erickson, T. S. Tylee, K. A. Guthrie, D. E. Furst, and J. L. Nelson
Male microchimerism in healthy women and women with scleroderma: cells or circulating DNA? A quantitative answer
Blood,
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[Abstract]
[Full Text]
[PDF]
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P. F. Penas, M. Jones-Caballero, M. Aragues, J. Fernandez-Herrera, J. Fraga, and A. Garcia-Diez
Sclerodermatous Graft-vs-Host Disease: Clinical and Pathological Study of 17 Patients
Arch Dermatol,
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924 - 934.
[Abstract]
[Full Text]
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Y. Endo, I. Negishi, and O. Ishikawa
Possible contribution of microchimerism to the pathogenesis of Sjogren's syndrome
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[Abstract]
[Full Text]
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L. I. Sakkas, B. Xu, C. M. Artlett, S. Lu, S. A. Jimenez, and C. D. Platsoucas
Oligoclonal T Cell Expansion in the Skin of Patients with Systemic Sclerosis
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[Abstract]
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Y. Zhang, L. L. McCormick, S. R. Desai, C. Wu, and A. C. Gilliam
Murine Sclerodermatous Graft-Versus-Host Disease, a Model for Human Scleroderma: Cutaneous Cytokines, Chemokines, and Immune Cell Activation
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[Abstract]
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R. Bolli
Regeneration of the Human Heart -- No Chimera?
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M. Imaizumi, A. Pritsker, P. Unger, and T. F. Davies
Intrathyroidal Fetal Microchimerism in Pregnancy and Postpartum
Endocrinology,
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[Abstract]
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A. Stevens and J. L. Nelson
Maternal and Fetal Microchimerism: Implications for Human Diseases
NeoReviews,
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M. D. Lockshin
Genome and Hormones: Gender Differences in Physiology: Invited Review: Sex ratio and rheumatic disease
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[Abstract]
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F CARLUCCI, R PRIORI, C ALESSANDRI, G VALESINI, and A STOPPACCIARO
Y chromosome microchimerism in Sjogren's syndrome
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K P MACHOLD and J S SMOLEN
Stem cell transplantation: limits and hopes
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[Abstract]
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I Toda, M Kuwana, K Tsubota, and Y Kawakami
Lack of evidence for an increased microchimerism in the circulation of patients with Sjogren's syndrome
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M. Imaizumi, A. Pritsker, M. Kita, L. Ahmad, P. Unger, and T. F. Davies
Pregnancy and Murine Thyroiditis: Thyroglobulin Immunization Leads to Fetal Loss in Specific Allogeneic Pregnancies
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Y.M. D. Lo, T. K. Lau, L. Y.S. Chan, T. N. Leung, and A. M.Z. Chang
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D. Nierhoff, H. C. Horvath, J. Mytilineos, M. Golling, O. Bud, E. Klar, G. Opelz, M. T. Voso, A. D. Ho, R. Haas, et al.
Microchimerism in bone marrow-derived CD34+ cells of patients after liver transplantation
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N. C. Lambert, P. C. Evans, T. L. Hashizumi, S. Maloney, T. Gooley, D. E. Furst, and J. L. Nelson
Cutting Edge: Persistent Fetal Microchimerism in T Lymphocytes Is Associated with HLA-DQA1*0501: Implications in Autoimmunity
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H. E. Vietor, E. Hallensleben, S. P. M. J. van Bree, E. M. W. van der Meer, S. E. J. Kaal, J. Bennebroek-Gravenhorst, H. H. H. Kanhai, A. Brand, and F. H. J. Claas
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J L. Nelson
Autoimmune disease and the long-term persistence of fetal and maternal microchimerism
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TOP
ABSTRACT
INTRODUCTION