Clinical implications of maternal-fetal cellular trafficking

https://doi.org/10.1053/j.sempedsurg.2012.10.011Get rights and content

Maternal-fetal cellular trafficking (MFCT) is the bidirectional passage of cells that results in the presence of fetal cells in the mother and maternal cells in the fetus. This naturally occurring biological phenomenon has been implicated in the pathogenesis of autoimmune diseases in both mothers and children. However, MFCT may also have beneficial consequences in establishing and maintaining maternal-fetal tolerance and may have long-term consequences for transplantation tolerance. There is also evidence that trafficking is altered during pregnancy complications and fetal intervention. An improved understanding of cellular trafficking during pregnancy will lead to progress in multiple fields including autoimmunity, transplantation, and fetal surgery.

Introduction

Maternal-fetal cellular trafficking (MFCT) is the bidirectional passage of cells between a mother and her fetus resulting in long-lived maternal cells in the fetus1 and fetal cells in the mother.2 The diagnostic potential of detecting fetal chromosomal abnormalities in maternal serum has led to extensive study of fetal-to-maternal cell trafficking (which results in fetal microchimerism, FMc, in mothers). Although the actual function of this trafficking is unknown, it is thought that fetal cells may trigger autoimmune disease3, 4, 5, 6 or play a regenerative role in maternal tissues after injury.7, 8 Similarly, maternal-to-fetal cellular trafficking (which results in maternal microchimerism (MMc), in fetuses) may have implications for the pathogenesis of autoimmune and other diseases in children. MMc may also lead to the development of long-lived tolerance to maternal antigens. In this review, we will summarize the potential role of FMc and MMc in maternal and pediatric disorders and explore the role of MMc in the development of maternal-fetal tolerance.

Section snippets

Fetal microchimerism

One of the earliest reports of FMc was from Georg Schmorl in the late 1800's, who identified placental trophoblast cells of fetal origin in mothers who died of eclampsia.9 Since these early findings, multiple reports have documented the presence of fetal cells and cell-free fetal DNA in maternal blood during normal pregnancy.10, 11, 12 The detection of cell-free fetal DNA, in particular, has been a major focus in the study of FMc given the obvious clinical application of detecting fetal

Maternal microchimerism

The first description of MMc was in 1963, when maternal leukocytes were identified in the cord blood of newborn infants.21 With the development of more sensitive PCR based assays, investigators have since identified long-lived maternal cells in healthy adult patients.1 More recent data has demonstrated the diverse tissue distribution of maternal cells, with reports of MMc in the blood, brain, heart, intestine, lungs, liver, muscle, pancreas, skin, and spleen.22, 23, 24, 25, 26, 27, 28, 29, 30,

Alterations in microchimerism after fetal intervention

The trafficking of fetal cells or cell-free DNA into the mother has been studied after fetal intervention. Fetal intervention may lead to changes in the placenta or fetal membranes, with resultant alterations in trafficking. Laser ablation of inter-twin vessels for twin–twin transfusion syndrome (TTTS) has been associated with increased levels of circulating fetal DNA in maternal circulation for up to 48 h after the procedure. In this study, elevated levels of fetal DNA at 24 h was associated

Conclusions and future directions

The role of MFCT in maternal and fetal health remains a fascinating yet unanswered question. Insights into this biological phenomenon will prove useful for understanding the origins of autoimmune conditions, transplantation tolerance, and maternal-fetal tolerance during pregnancy. Progress in our understanding of the clinical implications of MFCT will rely on our ability to understand the mechanism leading to trafficking as well as the mechanism by which trafficked cells contribute to disease.

References (70)

  • A.M. Stevens et al.

    Myocardial-tissue-specific phenotype of maternal microchimerism in neonatal lupus congenital heart block

    Lancet

    (2003)
  • C.J. Willer et al.

    Association between microchimerism and multiple sclerosis in Canadian twins

    J Neuroimmunol

    (2006)
  • A.M. Reed et al.

    Chimerism in children with juvenile dermatomyositis

    Lancet

    (2000)
  • C.M. Artlett et al.

    Chimeric cells of maternal origin in juvenile idiopathic inflammatory myopathies

    Lancet

    (2000)
  • K. Khosrotehrani et al.

    Presence of chimeric maternally derived keratinocytes in cutaneous inflammatory diseases of children: the example of pityriasis lichenoides

    J Invest Dermatol

    (2006)
  • J.M. Hall et al.

    Detection of maternal cells in human umbilical cord blood using fluorescence in situ hybridization

    Blood

    (1995)
  • J.F. Bastian et al.

    Maternal isoimmunisation resulting in combined immunodeficiency and fatal graft-versus-host disease in an infant

    Lancet

    (1984)
  • S.M. Muller et al.

    Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients

    Blood

    (2001)
  • A.M. Marleau et al.

    Chimerism of murine fetal bone marrow by maternal cells occurs in late gestation and persists into adulthood

    Lab Invest

    (2003)
  • C. Vernochet et al.

    Bi-directional cell trafficking between mother and fetus in mouse placenta

    Placenta

    (2007)
  • E. Roy et al.

    Specific maternal microchimeric T cells targeting fetal antigens in beta cells predispose to auto-immune diabetes in the child

    J Autoimmun

    (2011)
  • M. Stern et al.

    Survival after T cell-depleted haploidentical stem cell transplantation is improved using the mother as donor

    Blood

    (2008)
  • J.J. van Rood et al.

    Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus-host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling

    Blood

    (2002)
  • M. Hayashida et al.

    The evidence of maternal microchimerism in biliary atresia using fluorescent in situ hybridization

    J Pediatr Surg

    (2007)
  • H. Kobayashi et al.

    Maternal microchimerism in biliary atresia

    J Pediatr Surg

    (2007)
  • A. Nijagal et al.

    Decreased risk of graft failure with maternal liver transplantation in patients with biliary atresia

    Am J Transplant

    (2012)
  • T. Wataganara et al.

    Persistent elevation of cell-free fetal DNA levels in maternal plasma after selective laser coagulation of chorionic plate anastomoses in severe midgestational twin–twin transfusion syndrome

    Am J Obstet Gynecol

    (2005)
  • M.L. Tjoa et al.

    Circulating cell-free fetal messenger RNA levels after fetoscopic interventions of complicated pregnancies

    Am J Obstet Gynecol

    (2006)
  • S. Maloney et al.

    Microchimerism of maternal origin persists into adult life

    J Clin Invest

    (1999)
  • D.W. Bianchi et al.

    Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum

    Proc Natl Acad Sci U S A

    (1996)
  • K.L. Johnson et al.

    Microchimerism in a female patient with systemic lupus erythematosus

    Arthritis Rheum

    (2001)
  • K.L. Johnson et al.

    Fetal cell microchimerism in tissue from multiple sites in women with systemic sclerosis

    Arthritis Rheum

    (2001)
  • I.C. Kremer Hovinga et al.

    Pregnancy, chimerism and lupus nephritis: a multi-centre study

    Lupus

    (2008)
  • K.L. Johnson et al.

    Significant fetal cell microchimerism in a nontransfused woman with hepatitis C: evidence of long-term survival and expansion

    Hepatology

    (2002)
  • K. Khosrotehrani et al.

    Transfer of fetal cells with multilineage potential to maternal tissue

    JAMA

    (2004)
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