Maternal cell microchimerism in newborn tissues

Srivatsa, Bharath; Srivatsa, Sumathi; Johnson, Kirby L.; Bianchi, Diana W.

doi:10.1067/mpd.2003.mpd0327

Cited by 117 publications

(76 citation statements)

References 22 publications

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“…Whereas maternal cells have long been known to persist in immune-deficient children, it is only recently that long-term persistence of MMc in a mother's immune-competent children has been appreciated. MMc has been reported in infants in the thymus, liver, thyroid, skin (18), and heart (16) and in the peripheral blood of healthy adults (8). In an experimental model, maternal cells were found in the bone marrow of immune-competent mice during gestation and increased postnatally (19).…”

Section: Discussionmentioning

confidence: 97%

Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet β cell microchimerism

Nelson

Gillespie

Lambert

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

168

166

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Maternal cells have recently been found in the circulation and tissues of mothers' immune-competent children, including in adult life, and is referred to as maternal microchimerism (MMc). Whether MMc confers benefits during development or later in life or sometimes has adverse effects is unknown. Type 1 diabetes (T1D) is an autoimmune disease that primarily affects children and young adults. To identify and quantify MMc, we developed a panel of quantitative PCR assays targeting nontransmitted, nonshared maternal-specific HLA alleles. MMc was assayed in peripheral blood from 172 individuals, 94 with T1D, 54 unaffected siblings, and 24 unrelated healthy subjects. MMc levels, expressed as the genome equivalent per 100,000 proband cells, were significantly higher in T1D patients than unaffected siblings and healthy subjects. Medians and ranges, respectively, were 0.09 (0 -530), 0 (0 -153), and 0 (0 -7.9). Differences between groups were evident irrespective of HLA genotypes. However, for patients with the T1D-associated DQB1*0302-DRB1*04 haplotype, MMc was found more often when the haplotype was paternally (70%) rather than maternally transmitted (14%). In other studies, we looked for female islet ␤ cells in four male pancreases from autopsies, one from a T1D patient, employing FISH for X and Y chromosomes with concomitant CD45 and ␤ cell insulin staining. Female islet ␤ cells (presumed maternal) formed 0.39 -0.96% of the total, whereas female hematopoietic cells were very rare. Thus, T1D patients have higher levels of MMc in their circulation than unaffected siblings and healthy individuals, and MMc contributes to islet ␤ cells in a mother's progeny.quantitative PCR ͉ chimerism ͉ autoimmunity ͉ pancreas ͉ HLA

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Section: Discussionmentioning

confidence: 97%

Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet β cell microchimerism

Nelson

Gillespie

Lambert

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

168

166

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“…As suggested in studies of dermatomyositis (13), one consideration is that maternal microchimerism might affect a mother's progeny through anti-fetal alloreactive T cell responses. Female cells (presumed to be maternal) have been described in the tissues of male neonates (14), and an increase in the number of female cells has been reported in the muscle tissues of children with dermatomyositis (15) or idiopathic myositis (16). We recently identified maternal (female) cardiac myocytes in the heart muscle and atrioventricular node of male infants who died of heart block associated with neonatal lupus syndrome (17), suggesting the additional possibility that maternal cells could potentially be tissue targets of immune response (or, alternatively, could be involved in tissue repair).…”

Section: Discussionmentioning

confidence: 99%

Maternal HLA class II compatibility in men with systemic lupus erythematosus

Stevens

Tsao

Hahn

et al. 2005

Arthritis & Rheumatism

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Objective. Maternal-fetal cell transfer during pregnancy can lead to long-lasting microchimerism, which raises the question of whether microchimerism sometimes contributes to autoimmune disease later in life. In an experimental model, transfusion of parental lymphocytes homozygous for major histocompatibility complex alleles results in systemic lupus erythematosus (SLE). We identified male patients with SLE and healthy male subjects and their mothers in order to investigate the mother-son HLA relationship in SLE risk. Male subjects were selected in order to avoid confounding due to fetal microchimerism, which may occur in women.Methods. HLA genotyping for DRB1, DQA1, and DQB1 was conducted for sons and their mothers. Thirty men with SLE and their mothers were compared with 76 healthy men and their mothers.Results. Sons with SLE were HLA-identical with their mothers (bidirectionally compatible) for the basic HLA-DRB1 groups encoded by DRB1*01 through DRB1*14 more often than were healthy sons (odds ratio [OR] 5.0, P ‫؍‬ 0.006). Each DRB1 group contains multiple allelic variants; male patients with SLE and their mothers often were identical for both DRB1 allelic variants (OR 3.2, P ‫؍‬ 0.08). For DQA1 and DQB1, the ORs were 2.3 (P ‫؍‬ 0.08) and 2.0 (P ‫؍‬ 0.21), respectively. When analysis was limited to male subjects with SLEassociated HLA genes (encoding HLA-DR2 or HLA-DR3), the differences further increased for DRB1 basic groups (OR 7.2, P ‫؍‬ 0.01), DRB1 alleles (OR 15.0, P ‫؍‬ 0.018), DQA1 6.4 (P ‫؍‬ 0.006), and DQB1 (OR 5.7, P ‫؍‬ 0.027). No increase in (unidirectional) compatibility of the mother from the son's perspective was observed at any locus.Conclusion. We observed increased bidirectional HLA class II compatibility of male SLE patients and their mothers compared with healthy men and their mothers. This observation implies that maternal microchimerism could sometimes be involved in SLE and therefore merits further investigation.

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“…A recent study observed persistent maternal cells in liver, spleen, thymus, thyroid and skin of all four newborns examined who died from either chromosome abnormality or congenital malformation during the first week of life. This observation indicates that maternal cells entering the fetal circulation are capable of migration to fetal or neonatal organs, and this event may be quite common in abnormal fetuses 73 . Finally, results from an animal experiment indicated that maternal T cells of pregnant mice could cross the placenta and eventually induce antigen-specific immunological tolerance in the offspring 74 .…”

Section: Journal Of Maternal-fetal and Neonatal Medicinementioning

confidence: 99%

Neonates born to pre-eclamptic mothers have a higher percentage of natural killer cells (CD3 - /CD56+16+) in umbilical cord blood than those without pre-eclampsia

White

Ahlstrand²

2003

DJMF

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Objective: Maternal endothelial dysfunction and intravascular inflammation have been implicated in the mechanisms of disease responsible for the clinical syndrome of pre-eclampsia. Recently, the activation of the innate limb of the immune response (neutrophils and monocytes) in the fetal circulation has been reported in neonates born to mothers with pre-eclampsia. Natural killer (NK) cells are identified morphologically as a subpopulation of lymphocytes, but functionally as one component of the innate immune system. NK cells participate in the control of viral or bacterial infection, regulation of hematopoiesis, production of cytokines and cytotoxicity of neoplastic cells. Accumulating evidence suggests that the innate system is required for mounting an adequate adaptive response. NK cells, originally defined as effector cells of the innate immune system, may also play a role as regulatory cells for the adaptive immune system. This study was designed to determine the proportion of the NK cell subset of lymphocytes in umbilical cord blood of neonates born to mothers with and without pre-eclampsia. Methods: A cross-sectional study including neonates of mothers with (n = 48) and those without pre-eclampsia (control group) (n = 72) was conducted. Pre-eclampsia was diagnosed in the presence of hypertension and proteinuria. The control group consisted of neonates (premature and term) with no evidence of acute inflammation within the extraplacental membranes (chorioamnionitis). Umbilical cord blood was collected at the time of delivery, and assayed using monoclonal antibodies for selective cluster differentiation (CD) antigens in order to determine the proportion of NK cells as a percentage of total lymphocytes. The immunophenotypic characteristic was determined using flow cytometry, and NK cells were identified by positivity of CD16 and CD56 without CD3 (CD3-/CD56+16+). Log transformation of the percentage of NK cells was performed. Parametric statistics were used for analysis. Multiple regression analysis was utilized to examine the contribution of potentially confounding factors on the proportion of NK cells. A p value of < 0.05 was considered statistically significant. Results: Neonates born to mothers with pre-eclampsia had a significantly higher percentage of NK cells (CD3-/CD56+16+) than those in the control group (pre-eclampsia, mean ± SD 17 ± 9% vs. control, mean ± SD 12 ± 7.5%; p = 0.001). Multiple regression analysis suggested that umbilical cord blood pH of < 7.2, labor with vaginal delivery and maternal pre-eclampsia were associated with an increased percentage of NK cells in umbilical cord blood. Conclusions: Pre-eclampsia is associated with a higher NK cell (CD3-/CD56+16+) subset of lymphocytes in umbilical cord blood than in the control group. This difference cannot be explained by fetal acidosis or the presence of labor.

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Maternal cell microchimerism in newborn tissues

Cited by 117 publications

References 22 publications

Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet β cell microchimerism

Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet β cell microchimerism

Maternal HLA class II compatibility in men with systemic lupus erythematosus

Neonates born to pre-eclamptic mothers have a higher percentage of natural killer cells (CD3 - /CD56+16+) in umbilical cord blood than those without pre-eclampsia

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