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Microchimerism: The Depth and Breadth of Consequences for Human Health

J. Lee Nelson, MD

Some cells traffic between a mother and fetus during pregnancy. Surprisingly, small numbers of cells persist in respective hosts decades later.  Microchimerism (Mc) refers to an individual harboring a small number of cells, or DNA, derived from another individual. 

Our interdisciplinary research team goal is to identify the breadth of consequences of naturally-acquired Mc across all of human health.1  

Autoimmune Disease

In 1998 in the first study of Mc, elevated levels of fetal Mc in blood were found in women with scleroderma compared to healthy women.2 Fetal Mc has since been investigated in primary biliary cirrhosis, thyroiditis, Sjögren’s syndrome, polymorphic eruption of pregnancy and rheumatoid arthritis. Maternal Mc is found in her adult progeny.3 

Maternal Mc has been studied in neonatal lupus, systemic lupus and myositis. In infants with neonatal lupus and heart block, maternal cells were identified in the heart and were found to be cardiac myocytes4. Thus microchimeric cells could be targets for an immune response.

Alternatively, the microchimeric cells could be helpful by contributing to the repair of damaged tissues. Fetal Mc may be beneficial during pregnancy in women with rheumatoid arthritis, as elevated levels significantly correlated with pregnancy-induced amelioration of arthritis.5

Cancer

In hematopoietic cell transplantation (HCT) donor cells provide an advantage against recurrent leukemia and other malignancies. By analogy, we asked whether fetal Mc might be responsible for the protection from breast cancer observed in women who have had prior pregnancies, compared to those who have not. 

In other types of malignancies the converse question may be asked, whether microchimeric cells sometimes “go bad” and result in malignancy, as suggested in some anecdotal reports.

Infectious Disease

The T lymphocyte is a key determinant of immune reactions between one's own cells and foreign cells.  Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) are characterized by critical deficiencies in CD4+ T cells. 

To our knowledge, maternal Mc has never been examined in HIV and AIDS. We are investigating maternal Mc in men with HIV and will correlate results with whether there is progression or non-progression to AIDS.  

Transplantation 

Transplantation results in iatrogenic chimerism. Donor Mc has been proposed as facilitating graft acceptance. Until recently donor Mc was measured as male DNA in female recipients. It is now clear that women commonly have male DNA from prior pregnancies. In HCT, graft-vs-host disease occurs more often if the donor is a woman with prior pregnancies.

Female apheresis products were found to contain male Mc, consistent with the interpretation that fetal Mc contributes to graft-vs-host disease.6 In kidney, pancreas and islet transplantation we have tested serial serum samples and found that donor-specific microchimerism detection may become a useful non-invasive test for early rejection.7

Finally, several groups are now therapeutically exploiting the principles of naturally-acquired Mc in their selection of donors for HCT.

References

1. Adams KA, Nelson JL.  Microchimerism: An investigative frontier in autoimmunity and transplantation.  JAMA 291:1127-1131, 2004.

2. Nelson JL, Furst DE, Maloney S, Gooley T, Evans PC, Bean MA, Ober C, Smith AJ, Bianchi DW.  Microchimerism and HLA-compatible relationships of pregnancy in women with scleroderma. Lancet 351:559-62, 1998.

3. Maloney S, Smith AG, Furst DE, Myerson D, Rupert K, Evans PC, Nelson JL.  Microchimerism of maternal origin persists into adult life.  J Clin Invest 104:41-7, 1999.

4.  Stevens AM, Hermes H, Rutledge R, Buyon J, Nelson JL.  Maternal microchimerism has myocardial tissue-specific phenotype in neonatal lupus congenital heart block. Lancet 362:1617-23, 2003.

5. Yan Z, Ostensen M, Lambert NC, Guthrie KA, Nelson JL.  Prospective study of cell-free fetal DNA and disease activity during pregnancy in women with inflammatory arthritis.  Arthritis Rheum 54:2069-73, 2006.

6. Adams KM, Lambert NC, Heimfeld S, Tylee TS, Pang JM, Erickson TD, Nelson JL.  Male DNA in peripheral blood stem cell apheresis products of female donors.  Blood 15:3845-7, 2003.

7. Gadi, VK, Nelson JL, Boespflug N, Guthrie K, Kuhr C.  Soluble donor DNA concentrations in recipient serum correlates with pancreas-kidney rejection.  Clin Chem 52:379-82, 2006.