Maternal Microchimerism Research Articles

Exposure to HIV is associated with altered composition of maternal microchimeric T cells in infants.

HIV exposed but uninfected infants (iHEU) display altered immunity and are at increased risk of infection. We previously reported that iHEU have decreased maternal microchimerism (MMc)-maternal cells transferred to the offspring in utero/during breastfeeding. We quantified MMc in T cell subpopulations in iHEU and unexposed infants (iHU) to determine whether a selective deficiency in MMc contributes to altered cellular immunity. Across all infants, MMc levels were highest in CD8+ T cells; however, the level of CD8+ T cell MMc was lower in iHEU versus iHU. In limited functional studies, we did not identify CMV-specific MMc during infant primary infection.

Naturally acquired microchimerism: clinical, scientific and ethical issues

Microchimerism (MC) is understood as the presence in the body of cells genetically different from the population of the individual, capable of existence and persistence, that is, reproduction and differentiation. This process is associated with the exchange of cellular material between mother and fetus. The consequences of the intrauterine acquisition of maternal MC (MMC) by the fetus are essentially different from the acquisition by the mother of fetal CM (FMC) in the mature state of the organism. Microchimerism has been implicated in the development of autoimmune diseases, but it also helps the body limit a particular disease. Since all these processes take place during the early development of the fetal immune system, the initial response of the immune system is the development of specific tolerance to maternal antigens. MMС can modify immune functions and reactivity through the nongenetic acquisition of cellular and subcellular material. Both FMС and MMС are quite common phenomena, which affects the body of the child and mother, the differentiation and functionality of the host cells. All this allows us to consider foreign cells as a potential target for drugs in the fight against autoimmune diseases or, conversely, stimulation of regeneration processes of damaged tissues. Issues of evolution and prospects for the prevention of various pathological conditions are considered from the standpoint of taking into account maternal and fetal chimerism syndrome.

Deciphering the Role of Maternal Microchimerism in Offspring Autoimmunity: A Narrative Review.

Feto-maternal microchimerism is the bidirectional transfer of cells through the placenta during pregnancy that can affect the health of both the mother and the offspring, even in childhood or adulthood. However, microchimerism seems to have different consequences in the mother, who already has a developed immune system, than in the fetus, which is vulnerable with immature defense mechanisms. Studies have shown that the presence of fetal microchimeric cells in the mother can be associated with reduced fetal growth, pre-eclampsia, miscarriage, premature birth, and the risk of autoimmune disease development in the future. However, some studies report that they may also play a positive role in the healing of maternal tissue, in cancer and cardiovascular disease. There are few studies in the literature regarding the role of maternal microchimeric cells in fetal autoimmunity. Even fewer have examined their association with the potential triggering of autoimmune diseases later in the offspring's life. The objectives of this review were to elucidate the mechanisms underlying the potential association between maternal cells and autoimmune conditions in offspring. Based on our findings, several hypotheses have been proposed regarding possible mechanisms by which maternal cells may trigger autoimmunity. In Type 1 diabetes, maternal cells have been implicated in either attacking the offspring's pancreatic β-cells, producing insulin, differentiating into endocrine and exocrine cells, or serving as markers of tissue damage. Additionally, several potential mechanisms have been suggested for the onset of neonatal lupus erythematosus. In this context, maternal cells may induce a graft-versus-host or host-versus-graft reaction in the offspring, function as effectors within tissues, or contribute to tissue healing. These cells have also been found to participate in inflammation and fibrosis processes, as well as differentiate into myocardial cells, potentially triggering an immune response. Moreover, the involvement of maternal microchimeric cells has been supported in conditions such as juvenile idiopathic inflammatory myopathies, Sjögren's syndrome, systemic sclerosis, biliary atresia, and rheumatoid arthritis. Conversely, no association has been found between maternal cells and celiac disease in offspring. These findings suggest that the role of maternal cells in autoimmunity remains a controversial topic that warrants further investigation.

Maternal-Fetal Microchimerism: Impacts on Offspring's Immune Development and Transgenerational Immune Memory Transfer.

Maternal-fetal microchimerism is a fascinating phenomenon in which maternal cells migrate to the tissues of the offspring during both pregnancy and breastfeeding. These cells primarily consist of leukocytes and stem cells. Remarkably, these maternal cells possess functional potential in the offspring and play a significant role in shaping their immune system development. T lymphocytes, a cell population mainly found in various tissues of the offspring, have been identified as the major cell type derived from maternal microchimerism. These T lymphocytes not only exert effector functions but also influence the development of the offspring's T lymphocytes in the thymus and the maturation of B lymphocytes in the lymph nodes. Furthermore, the migration of maternal leukocytes also facilitates the transfer of immune memory across generations. Maternal microchimerism has also been observed to address immunodeficiencies in the offspring. This review article focuses on investigating the impact of maternal cells transported within maternal microchimerism on the immune system development of the offspring, as well as elucidating the effector functions of maternal cells that migrate through the placenta and breast milk to reach the offspring.

IL-2Rα KO mice exhibit maternal microchimerism and reveal nuclear localization of IL-2Rα in lymphoid and non-lymphoid cells.

IL-2Rα knock out (KO) mice have been instrumental to discovering the immunoregulatory properties of IL-2Rα. While initially thought of only as a stimulatory cytokine, IL-2 and IL-2Rα KO mice revealed that this cytokine-receptor system controls immune responses through restimulation-induced cell death and by promoting the survival of T regulatory cells. Although described mostly in the context of lymphocytes, recent studies by our laboratory showed that IL-2R is expressed in smooth muscle cells. Given this finding, we sought to use IL-2Rα KO to determine the function of this receptor in vascular smooth muscle cells. Surprisingly, we found that IL-2Rα KO vascular smooth muscle cells had detectable IL-2Rα. We used multiple gene and protein-based methods to determine why IL-2Rα KO vascular smooth muscle cells exhibited IL-2Rα protein. These methods included: genomic sequencing, assessing cells and tissues for evidence of maternal microchimerism, and determining the half-life of IL-2Rα protein. Our studies demonstrated the following: (1) in addition to the cell surface, IL-2Rα is localized to the nucleus; (2) the genetic deletion of IL-2Rα is intact in IL-2Rα KO mice; (3) both IL-2Rα KO and WT tissues show evidence of maternal microchimerism, the likely source of IL-2Rα (4) IL-2Rα is transmitted between cells; (5) IL-2Rα has a long half-life; and (6) nuclear IL-2Rα contributes to the regulation of cell proliferation and size. Our findings suggest that the phenotype of complete IL-2Rα loss is more severe than demonstrated by IL-2Rα KO mice, and that IL-2Rα plays a here-to-fore unrecognized role in regulating cell proliferation in non-lymphoid cells.

Development and comparison of immunologic assays to detect primary RSV infections in infants.

Effective respiratory syncytial virus (RSV) vaccines have been developed and licensed for elderly adults and pregnant women but not yet for infants and young children. The RSV immune state of the young child, i.e., previously RSV infected or not, is important to the conduct and interpretation of epidemiology studies and vaccine clinical trials. To address the need for sensitive assays to detect immunologic evidence of past infection, we developed, characterized, and evaluated 7 assays including 4 IgG antibody enzyme immunoassays (EIAs), two neutralizing antibody assays, and an IFN-γ EliSpot (EliSpot) assay. The four IgG EIAs used a subgroup A plus subgroup B RSV-infected Hep-2 cell lysate antigen (Lysate), an expressed RSV F protein antigen (F), an expressed subgroup A G protein antigen (Ga), or an expressed subgroup B G protein (Gb) antigen. The two neutralizing antibody assays used either a subgroup A or a subgroup B RSV strain. The EliSpot assay used a sucrose cushion purified combination of subgroup A and subgroup B infected cell lysate. All seven assays had acceptable repeatability, signal against control antigen, lower limit of detection, and, for the antibody assays, effect of red cell lysis, lipemia and anticoagulation of sample on results. In 44 sera collected from children >6 months after an RSV positive illness, the lysate, F, Ga and Gb IgG EIAs, and the subgroup A and B neutralizing antibody assays, and the EliSpot assays were positive in 100%, 100%, 86%, 95%, 43%, and 57%, respectively. The Lysate and F EIAs were most sensitive for detecting RSV antibody in young children with a documented RSV infection. Unexpectedly, the EliSpot assay was positive in 9/15 (60%) of PBMC specimens from infants not exposed to an RSV season, possibly from maternal microchimerism. The Lysate and F EIAs provide good options to reliably detect RSV antibodies in young children for epidemiologic studies and vaccine trials.

Quantification of Female Chimeric Cells in the Tonsils of Male Children and Their Determinants.

The factors influencing mother-to-child cell trafficking and persistence over children's lives have yet to be established. The quantification of maternal microchimerism was previously reported through HLA-based approaches, which introduced bias regarding the tolerogenic environment. We aimed to identify cells of maternal origin irrespective of the HLA repertoire and to ascertain the determinants of microchimeric cells. This case-control study enrolled 40 male infants attending pediatric surgery from January 2022 to October 2022. Female cells were quantified in infants' tonsil tissue by using cytogenetic fluorescent in situ hybridization (FISH) coupled with optimized automated microscopy. Out of the 40 infants, half (47.4%) had been breastfed for more than one month, a quarter for less a month, and 10 children (26.3%) were never breastfed. XX cells were observed in male tonsils in two-thirds of participants at a median density of 5 cells per 100,000 cells. In univariate analyses, child age was negatively associated with a high female cell density. In exploratory multivariate analyses, previous breastfeeding is a likely determinant of the persistence of these cells in the host, as well as the rank among siblings. Part of the benefit of breastmilk for child health may therefore be driven by breastfeeding-related microchimerism.

In utero position matters for littermate cell transfer in mice: an additional and confounding source with maternal microchimerism.

Feto-maternal cell transfer during pregnancy is called microchimerism (Mc). Its persistence in respective hosts is increasingly studied as to its potential role in immune tolerance, autoimmunity, cancer, and degenerative diseases. Murine models with transgenic reporter genes, heterozygously carried by the mother, allow maternal Mc tracking in wild-type (WT) offspring. However, as gestation in mice is multi-embryonic, an exchange of cells between fetuses carrying the same reporter gene as their mother and negative WT littermate, named littermate Mc (LMc), can occur and be confounded with the maternal source. We propose here to evaluate LMc contribution in mice. To avoid the maternal confounding source of Mc, transgenic males, heterozygous for a reporter gene, here, the human leukocyte antigen DRB1*04 (DR4+/-), were crossed with WT females (DR4-/-). DR4+/- LMc was specifically quantified by HLA-DR4 quantitative PCR, i) in utero in main organs from 15 DR4-/- fetuses from three litters of 11, nine, and five; and ii) after birth in two litters of eight pups: in two DR4-/- stillborns and four DR4-/- adult mice. At embryonic stages, DR4-/- fetuses having one or two nearby DR4+/- littermates in the same uterine horn were almost seven times more frequently positive for DR4- microchimerism in their organs (p = 0.01) and had quantitatively more LMc (p = 0.009) than those without nearby DR4+/- littermates. Furthermore, LMc persists at birth and into adulthood with interindividual heterogeneity. This study identifies heterogeneity for LMc acquisition according to in utero position and different interpretation of previously published results on maternal Mc in mice.

Maternal microchimerism in a 2-years old boy with IL2R gamma chain deficiency

BackgroundAccording to the literature, 40% of patients with SCID have maternal microchimerism. MethodsWe reported a case of a 2-year-old boy with X-linked SCID caused by a mutation in the IL2RG gene. ResultsTo search for a donor and subsequent HSCT, HLA genotyping of leukocytes from peripheral blood for class I and II by SBT method was performed. The HLA-I results were as follows: A*02:01,03:01,B*07:02,18:01, C*05:01,07:02. The results for class II were questionable, as an additional allele was identified at the DQB1 locus.To exclude contamination, typing was carried out with another sample of leukocytes. The result was a complete confirmation of the primary data for class I; for class II, the result could not be interpreted. To exclude the admixture of maternal lymphocytes in the patient’s peripheral blood samples, HLA genotyping of the buccal epithelium was performed: it turned out to be impossible to identify alleles at the DQB1 and DRB1 loci. Subsequently, it turned out that the child was periodically breastfed, which could cause the presence of maternal cells in the buccal epithelium.From all of the above, it is likely that problems in identifying the patient’s HLA genotype could be related to the phenomenon of maternal microchimerism.To differentiate chimerism from mosaicism, a molecular genetic analysis of STR loci of the patient and his parents was performed. The results demonstrated that the patient’s blood sample contained an admixture of maternal cells, indicating the presence of maternal microchimerism. Molecular genetic study data confirmed the results of cytogenetic analysis by FISH. The study of lymphocytes from the patient’s peripheral blood and bone marrow revealed that 49% and 92% of the cells, respectively, had a karyotype XX. Buccal epithelium was examined to exclude the constitutional nature of mosaicism by sex chromosomes: it was found that all buccal epithelial cells had a karyotype XY.After the results of the cytogenetic study, we repeated HLA typing of buccal epithelium DQB1 and DRB1 loci. The following results were obtained during genotyping: DRB1*03:01,11:01,DQB1*02:01,03:01, thus the patient’s HLA genotype was established.Results of the analysis of short tandem repeats (STR loci) of the patient and his parentsStudied loci DNABlood sampleBuccal epithelium sample of patientfather№allele/№allelemothers№allele/№allelepatient№allele/№allelefor a period of breastfeeding№allele/№allelewithout maternal cells№allele/№alleleD3S135815/1714/1814/17/18*14/17/18*14/17vWA17/1717/1917/17/19*17/17/19*17/17D16S53910/1311/1210/11/12*10/11/12*10/11D2S133821/2418/2518*/21/2518*/21/2521/25amelogeninXYXXXYXYXYD8S117912/1210/1210/1210/1210/12D21S1129/3029/30.229/30/30.2*29/30/30.2*29/30D18S5111/1812/1811/12*/1811/12*/1811/18D19S43315/1614/1514*/15/1514*/15/1515/15TH016/97/76/76/76/7FGA22/2421/2221/22*/2421/22*/2421/24*additional allele.Results of HLA-genotyping of the patient and his parentsInvestigation of the HLA- lociGenotype of the fatherGenotype of the motherGenotype of the patientHLA-AA*03:01, 24:02A*02:01, 23:01A*02:01, 03:01HLA-BB*07:02,15:17B*18:01, 51:01B*07:02,18:01HLA-CC*07:01, 07:02C*05:01,15:02C*05:01, 07:02HLA-DRB1DRB1* 11:01, 11:03DRB1* 01:01, 03:01DRB1* 03:01, 11:01HLA-DQB1DQB1* 03:01, 03:01DQB1* 02:01, 05:01DQB1* 02:01, 03:01 ConclusionsThe presence of maternal microchimerism can make it difficult to perform HLA genotyping in patients with SCID.

Emergent roles of maternal microchimerism in postnatal development.

Maternal microchimerism (MMc) is the phenomenon that a low number of cells from the mother persists within her progeny. Despite their regular presence in mammalian pregnancies, the overall cell type repertoire and roles of maternal cells, especially after birth, remain unclear. By using transgenic mouse strains and human umbilical blood samples, recent studies have for the first time characterized and quantified MMc cell type repertoires in offspring, identified the cross-generational influence on fetal immunity, and determined possible factors that affect their presence in offspring. This review summarizes new findings, especially on the maternal cell type repertoires and their potential role in utero, in postnatal life, and long after birth.

Physiological and Pathological Effects of Fetal and Maternal Microchimerism

Microchimerism (Mc) is a bidirectional exchange of fetal and maternal cells during pregnancy. Pregnancy is the most common and natural cause of chimerism. Therefore, we are all born as microchimera. Although there are many unanswered questions it is thought that chimerism has an important role in human health. For many years, the clinical effects of microchimeric cells (McCs) in organ repair and cancer therapy have just begun to be understood. While the mission of chimerism is straight forward, the subject is profound. Chimerism carries the potential for disease as well as for health benefits. This article describes the role of Mc in the etiology of psychotic disorders. In this review, we consider Mc to be a physiological phenomenon, but it can also transform into pathology under inappropriate conditions. We describe in detail below the possible physio-pathological roles of F-MMcCs.

Umbilical Cord Maternal Microchimerism in Normal and Preeclampsia Pregnancies.

Bidirectional exchange of cells between mother and fetus establishes microchimerism (Mc). Mc can persist for decades and is associated with later-life health and disease. Greater fetal Mc is detected in the maternal compartment in preeclampsia (PE), but whether maternal Mc (MMC) in umbilical cord blood (CB) is altered in PE is unknown. We evaluated MMc in CB from normal and PE pregnancies. DNA from CB mononuclear cells following placental delivery (n = 36 PE, n = 37 controls) and maternal blood was extracted and genotyped. MMc, quantified by qPCR assays targeting maternal-specific nonshared polymorphisms in CB, was compared using logistic and negative binomial regression models. Clinically and statistically relevant confounders were included, and included the total number of cell equivalents tested, gravidity, mode of delivery, birthweight, and fetal sex. PE participants delivered at earlier gestational ages, with higher Cesarean rates, and lower infant birthweights. CB MMc detection was similar between PE and controls (52.8% vs. 51.3%, respectively, p = 0.90) and unchanged after adjustment for confounders. MMc concentration was not different between groups (mean 73.7 gEq/105gEq in PE vs. mean 22.8 gEq/105 in controls, p = 0.56), including after controlling for confounders (p = 0.64). There was no difference in CB MMc detection or concentration between PE and normal pregnancies, despite previously noted greater fetal Mc in the maternal compartment. This suggests possible differential transfer of cells at the maternal fetal interface in PE. Phenotypic evaluation of Mc cells may uncover underlying mechanisms for differential cellular exchange between mother and fetus in PE.

New insights in understanding biliary atresia from the perspectives on maternal microchimerism.

Biliary atresia (BA) is a fibroinflammatory cholangiopathy and portal venopathy. It is of unknown etiology and is associated with systemic immune dysregulation, in which the first insult begins before birth. Maternal microchimerism is a naturally occurring phenomenon during fetal life in which maternal alloantigens promote the development of tolerogenic fetal regulatory T-cells in utero. However, maternal cells may alter the fetus’s response to self-antigens and trigger an autoimmune response under certain histocompatibility combinations between the mother and the fetus. A recent report on a set of dizygotic discordant twins with BA, one of whose placentae showed villitis of unknown etiology, implies a certain immune-mediated conflict between the fetus with BA and the mother. Maternal chimeric cells persist postnatally for various time spans and can cause cholangitis, which ultimately leads to liver failure. In contrast, patients who eliminate maternal chimeric cells may retain their liver function.

Pregnancy-induced maternal microchimerism shapes neurodevelopment and behavior in mice

Life-long brain function and mental health are critically determined by developmental processes occurring before birth. During mammalian pregnancy, maternal cells are transferred to the fetus. They are referred to as maternal microchimeric cells (MMc). Among other organs, MMc seed into the fetal brain, where their function is unknown. Here, we show that, in the offspring’s developing brain in mice, MMc express a unique signature of sensome markers, control microglia homeostasis and prevent excessive presynaptic elimination. Further, MMc facilitate the oscillatory entrainment of developing prefrontal-hippocampal circuits and support the maturation of behavioral abilities. Our findings highlight that MMc are not a mere placental leak out, but rather a functional mechanism that shapes optimal conditions for healthy brain function later in life.

Factors influencing maternal microchimerism throughout infancy and its impact on infant T cell immunity.

Determinants of the acquisition and maintenance of maternal microchimerism (MMc) during infancy and the impact of MMc on infant immune responses are unknown. We examined factors that influence MMc detection and level across infancy and the effect of MMc on T cell responses to bacillus Calmette-Guérin (BCG) vaccination in a cohort of HIV-exposed, uninfected and HIV-unexposed infants in South Africa. MMc was measured in whole blood from 58 infants using a panel of quantitative PCR assays at day 1, and 7, 15, and 36 weeks of life. Infants received BCG at birth, and selected whole blood samples from infancy were stimulated in vitro with BCG and assessed for polyfunctional CD4+ T cell responses. MMc was present in most infants across infancy, with levels ranging from 0 to 1,193/100,000 genomic equivalents and was positively impacted by absence of maternal HIV, maternal and infant HLA compatibility, infant female sex, and exclusive breastfeeding. Initiation of maternal antiretroviral therapy prior to pregnancy partially restored MMc level in HIV-exposed, uninfected infants. Birth MMc was associated with an improved polyfunctional CD4+ T cell response to BCG. These data emphasize that both maternal and infant factors influence the level of MMc, which may subsequently affect infant T cell responses.

Biliary atresia: graft-versus-host disease with maternal microchimerism as an etiopathogenesis

Biliary atresia (BA) is an inflammatory disease of the biliary system in newborns and infants. The etiology is largely unknown. Approximately half of BA patients require liver transplantation by 20 years of age, even after surgical correction due to progressive fibrosis of the liver. Regarding the disease mechanism, there is circumstantial evidence to support the hypothesis of graft-versus-host disease because of the existence of maternal cells in the liver (maternal microchimerism, MMC), histopathological similarity of the liver and an intense maternal response to the BA patient with mixed lymphocyte culture. Immune dysregulation with decreased Treg and increased Th1 and Th17 cells are the pathogenic features of BA, which are homologous to the pathogenic features of GvHD.Further elucidation of the etiopathogenetic mechanism of BA is warranted for development of new therapeutic strategies for native liver survival.

Quantification of Maternal Microchimeric Cells in the Liver of Children With Biliary Atresia.

Biliary atresia (BA) is a rare disorder of unknown etiology. There is a debate as to whether maternal microchimerism plays a significant role in the development of BA or in graft tolerance after liver transplantation. Here, we performed quantitative-PCR-based assays for liver tissues of children with BA and other diseases. Maternal cells were detected in 4/13 and 1/3 of the BA and control groups, respectively. The estimated number of maternal cells ranged between 0 and 34.7 per 106 total cells. The frequency and severity of maternal microchimerism were similar between the BA and control groups, and between patients with and without acute rejection of maternal grafts. These results highlight the high frequency of maternal microchimerism in the liver. This study provides no evidence for roles of microchimerism in the etiology of BA or in graft tolerance. Thus, the biological consequences of maternal microchimerism need to be clarified in future studies.

Grandmaternal cells in cord blood

sBackgroundDuring pregnancy a feto-maternal exchange of cells through the placenta conducts to maternal microchimerism (Mc) in the child and fetal Mc in the mother. Because of this bidirectional traffic of cells, pregnant women have also acquired maternal cells in utero from their mother and could transfer grandmaternal (GdM) cells to their child through the maternal bloodstream during pregnancy. Thus, cord blood (CB) samples could theoretically carry GdMMc. Nevertheless this has never been demonstrated.MethodsUsing Human Leukocyte Antigen (HLA)-specific quantitative PCR assays on three-generation families, we were able to test 28 CB samples from healthy primigravid women for GdMMc in whole blood (WB) and isolated cells (PBMC, T, B, granulocytes, stem cells).FindingsFive CB samples (18%) had GdMMc which could not be confounded with maternal source, with quantities 100 fold lower than maternal Mc in WB and PBMC. Risk of aneuploidies and/or related invasive prenatal procedures significantly correlated with the presence of GdMMc in CB (p=0.024). Significantly decreased HLA compatibility was observed in three-generation families from CB samples carrying GdMMc (p=0.019).InterpretationTransgenerational transfer of cells could have implications in immunology and evolution. Further analyses will be necessary to evaluate whether GdMMc in CB is a passive or immunologically active transfer and whether invasive prenatal procedures could trigger GdMMc.FundingProvence-Alpes-Côte d'Azur APEX grant # 2012_06549E, 2012_11786F and 2014_03978) and the Foundation for Medical Research (FRM Grant #ING20140129045).

Increased microchimerism in peripheral blood of women with systemic lupus erythematosus: relation with pregnancy.

We aimed to determine the presence, amount and origin of microchimerism in peripheral blood of pregnant and non-pregnant parous women with systemic lupus erythematosus (SLE) as compared to control subjects. We performed a comparative study in which peripheral blood was drawn from eleven female non-pregnant SLE-patients and 22 control subjects, and from six pregnant SLE-patients and eleven control subjects during gestation and up to six months postpartum. Quantitative PCR for insertion-deletion polymorphisms and null alleles was used to detect microchimerism in peripheral blood mononuclear cells and granulocytes. Microchimerism was detected more often in non-pregnant SLE-patients than control subjects (54.4% vs. 13.6%, respectively; p=0.03). When present, the median total number of foetal chimeric cells was 5 gEq/106 in patients and 2.5gEq/106 in control subjects (p=0.048). Microchimerism was mostly foetal in origin; maternal microchimerism was detected in one patient and one control subject. In control subjects, microchimerism was always derived from only one source whereas in 50% of patients it originated from multiple sources. The pregnant patients had a significantly higher median number of foetal chimeric cells in the granulocyte fraction just after delivery than control subjects (7.5 gEq/106 vs. 0 gEq/106, respectively; p=0.02). Just after delivery, SLE-patients had more microchimerism than control subjects. Three months post-partum, microchimerism was no longer detectable, only to reappear many years after the last pregnancy, more often and at higher levels in SLE-patients than in control subjects. This suggests that these chimeric cells may originate from non-circulating foetal chimeric stem cells.

Peripheral Plasmodium falciparum Infection in Early Pregnancy Is Associated With Increased Maternal Microchimerism in the Offspring.

Placental malaria has been associated with increased cord blood maternal microchimerism (MMc), which in turn may affect susceptibility to malaria in the offspring. We sought to determine the impact of maternal peripheral Plasmodium falciparum parasitemia during pregnancy on MMc and to determine whether maternal cells expand during primary parasitemia in the offspring. We conducted a nested cohort study of maternal-infant pairs from a prior pregnancy malaria chemoprevention study. Maternal microchimerism was measured by quantitative polymerase chain reaction targeting a maternal-specific marker in genomic DNA from cord blood, first P falciparum parasitemia, and preparasitemia. Logistic and negative binomial regression were used to assess the impact of maternal peripheral parasitemia, symptomatic malaria, and placental malaria on cord blood MMc. Generalized estimating equations were used to assess predictors of MMc during infancy. Early maternal parasitemia was associated with increased detection of cord blood MMc (adjusted odds ratio = 3.91, P = .03), whereas late parasitemia, symptomatic malaria, and placental malaria were not. The first parasitemia episode in the infant was not associated with increased MMc relative to preparasitemia. Maternal parasitemia early in pregnancy may increase the amount of MMc acquired by the fetus. Future work should investigate the impact of this MMc on immune responses in the offspring.