Studies - General Research

Past Abortion Might be a Factor in Autoimmune Diseases (2001-2007)

Summary: Past Abortion Might be a Factor in Autoimmune Diseases
Larger than normal feto-maternal transfer of cells occurs after an abortion.

Factor in autoimmune diseases.

In human pregnancies, bi-directional transfer of living maternal and embryonic cells begins with the implantation of the embryo and continues throughout the pregnancy.

Maternal cells pass into the fetal circulation and fetal cells pass into the maternal circulation. When fetal cells enter into the mother's circulation, they can exist via reproduction in maternal tissues for decades after the pregnancy and lead to fetal microchimerism (FMc).

Maternal cells also enter into the fetal circulation, where they can exist via reproduction in the child's tissues long after birth of the child, even into adulthood and lead to maternal microchimerism (MMc).1

Studies have found that MMc in a newborn is usually benign or beneficial, but is associated with a spectrum of chronic inflammatory diseases.1

In addition to a child acquiring the MMc directly from his/her mother, microchimerism is also possible to be derived from an older sibling.

Cells originating from the gestation of an older sibling could exist via uterine placental connection to the fetus of a subsequent pregnancy.1 A 2001 study found that a larger than normal fetomaternal transfer of cells occurs after an abortion.2,3

Subsequent analysis of published research, that included pregnancy history information, concluded that fetal loss was significantly associated with the development of microchimerism.4

Additionally, the effect of procreation with multiple partners has been identified as a possible influence on the development of microchimerism. Researchers found that women who had children with more than one partner had higher mortality rates than those who had only a single partner.2

Furthermore, it has been suggested that MMc is more likely to occur with elective terminations of pregnancy than with spontaneous miscarriages.5

It has been theorized that the persistence of fetal cells following pregnancy can lead to maternal immune responses to these immunologically foreign cells and may contribute to postpartum autoimmune diseases.2

Other studies have suggested that fetal cell microchimerism may occur in a much wider spectrum.2

1 Stevens, Anne M. Do Maternal Cells Trigger or Perpetuate Autoimmune Diseases in Children? Pediatric Rheumatology. May 2007.

2 Johnson, Kirby L., Diana W. Bianchi. Fetal Cells in Maternal Tissue Following Pregnancy: What Are the Consequences? Human Reproduction Update. 10(6) 497-502. August 2004.

3 Bianchi, Diana W., Antonio Farina, William Weber, Laurent D. Delli-Bovi, Matthew DeRiso, John M. Williams, and Katherine W. Klinger. Significant Fetal-Maternal Hemorrhage After Termination of Pregnancy: Implications for Development of Fetal Cell Microchimerism. American Journal of Obstetrics & Gynecology. 2001.

4 Khosrotehrani, Kiarash, Kirby L. Johnson, Joseph Lau, Alain Dupuy, Dong Hyun Cha, and Diana W. Bianchi. The Influence of Fetal Loss on the Presence of Fetal Cell Microchimerism. Arthritis & Rheumatism. November 2003. 48(11) 3237-3241.

5 McGrath, Jr. Hugh. Letter to the Editor, Arthritis & Rheumatism, September 2004, 50(9) 3058-3059.


Male microchimerism in women without sons: quantitative assessment and correlation with pregnancy history.

Am J Med. 2005 Aug;118(8):899-906.  

Yan Z, Lambert NC, Guthrie KA, Porter AJ, Loubiere LS, Madeleine MM, Stevens AM, Hermes HM, Nelson JL.

    Program in Human Immunogenetics, Fred Hutchinson Cancer Research Center, Seattle, Wash 98109, USA. [email protected]

    PURPOSE: Fetal microchimerism, derived from fetal cells that persist after pregnancy, is usually evaluated by tests for male microchimerism in women who gave birth to sons. We investigated male microchimerism in women without sons and examined correlation with prior pregnancy history. Immunologic consequences of microchimerism are unknown. We studied healthy women and women with rheumatoid arthritis (RA).

METHODS: Y-chromosome-specific real-time quantitative polymerase chain reaction was used to test peripheral blood mononuclear cells of 120 women (49 healthy and 71 with RA). Results were expressed as the number of male cells that would be equivalent to the total amount of male DNA detected within a sample containing the equivalent of 100000 female cells.

RESULTS: Male microchimerism was found in 21% of women overall. Healthy women and women with RA did not significantly differ (24% vs 18%). Results ranged from the DNA equivalent of 0 to 20.7 male cells per 100000 female cells. Women were categorized into 4 groups according to pregnancy history. Group A had only daughters (n = 26), Group B had spontaneous abortions (n = 23), Group C had induced abortions (n = 23), and Group D were nulligravid (n = 48). Male microchimerism prevalence was significantly greater in Group C than other groups (8%, 22%, 57%, 10%, respectively). Levels were also significantly higher in the induced abortion group.

CONCLUSIONS: Male microchimerism was not infrequent in women without sons. Besides known pregnancies, other possible sources of male microchimerism include unrecognized spontaneous abortion, vanished male twin, an older brother transferred by the maternal circulation, or sexual intercourse. Male microchimerism was significantly more frequent and levels were higher in women with induced abortion than in women with other pregnancy histories. Further studies are needed to determine specific origins of male microchimerism in women.

    PMID: 16084184 [PubMed – indexed for MEDLINE

    Comment in:
        Arthritis Rheum. 2004 Sep;50(9):3058-9; author reply 3059.

The influence of fetal loss on the presence of fetal cell microchimerism: a systematic review.
Arthritis Rheum. 2003 Nov;48(11):3237-41.   

Khosrotehrani K, Johnson KL, Lau J, Dupuy A, Cha DH, Bianchi DW.


nbsp;  Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.

    OBJECTIVE: Fetal cells enter the maternal circulation during most pregnancies. Their persistence for years occurs in only some women and has been associated with several autoimmune diseases such as systemic sclerosis. The objective of this study was to determine whether pregnancy history influences the persistence of fetal microchimeric cells.

METHODS: We reviewed all reports of studies on fetal cell microchimerism, defined as male DNA in maternal tissue, that describe individual pregnancy histories, disease diagnoses, and microchimerism status. The total numbers of pregnancies, births, and sons, the history of fetal loss (spontaneous abortion and elective termination), and the presence of a maternal autoimmune disease were tested as factors potentially associated with persistent microchimerism.

RESULTS: One hundred twenty-four subjects from 11 studies met the inclusion criteria. Only fetal loss was significantly associated with the presence of microchimerism (odds ratio 2.4, 95% confidence interval 1.2-6.0).

CONCLUSION: These results suggest that fetomaternal cell trafficking following fetal loss may be important for the engraftment of microchimeric cells in maternal tissue. This may be due to an increased amount of fetomaternal transfusion or to transfer of a cell type that is more likely to engraft. We recommend that investigators in future studies on microchimerism report detailed pregnancy information, since these data are critical for the understanding of factors that influence the development of fetal cell microchimerism.

    PMID: 14613289 [PubMed – indexed for MEDLINE]


Significant fetal-maternal hemorrhage after termination of pregnancy: implications for development of fetal cell microchimerism.

Am J Obstet Gynecol. 2001 Mar;184(4):703-6.  

Bianchi DW, Farina A, Weber W, Delli-Bovi LC, Deriso M, Williams JM, Klinger KW.

    Division of Genetics and the Department of Pediatrics, Tufts University School of Medicine, Genzyme Genetics, Framingham, Massachusetts, USA.

    OBJECTIVE: Recent reports that an association exists between fetal cell microchimerism and autoimmune disease has increased interest in the postpartum persistence of fetal cells. The purpose of this study was to determine, by means of quantitative polymerase chain reaction amplification, whether a significant fetalmaternal hemorrhage occurs after elective termination of pregnancy.

STUDY DESIGN: Blood samples were obtained from 23 women who underwent termination of pregnancy immediately before venipuncture; these samples were subjected to analysis by quantitative polymerase chain reaction amplification with the use of Y-chromosome primers. There were 21 male and 2 female fetuses. Results were equilibrated to 16 mL and analyzed by a weighted linear regression analysis to evaluate the correlation between detected fetal nucleated cell equivalents and gestational weeks.

RESULTS: Among the 21 known male fetuses, the median number of detected fetal nucleated cell equivalents was 1552 (range, 50-37,618). The female fetuses had no fetal nucleated cell equivalents detected. A positive dependence of male fetal nucleated cell equivalents on gestational age was shown (P <.001).

CONCLUSION: Analysis by quantitative polymerase chain reaction amplification demonstrated a large fetal-maternal transfusion after elective abortion. Consideration of the biologic consequences of pregnancy and the potential for future development of fetal cell microchimerism must now extend to a larger population of women.

    PMID: 11262475 [PubMed – indexed for MEDLINE]