Wednesday, 27.05.2026, Day 1
Time: 09:20 – 10:15
Microchimerism: Past, Present and Future
Diana W. Bianchi, MD
NIH/NHGRI, Washington D.C., USA
In 1977 when British musician Peter Frampton wrote a song called “I’m in You (You’re in Me)” he was presumably being metaphorical. He didn’t realize that a century earlier the German pathologist Georg Schmorl visualized the presence of placental-derived multi-nucleated syncytial giant cells in the organs of pregnant women who died of eclampsia. This led to the concept of microchimerism, in which the pregnant or post-partum woman acquires cells from her fetus that may persist in her body for decades. Named for the chimera, a Greek mythical animal with a lion’s head, a goat’s body, and the tail of a serpent, there was a resurgence of interest in the late 20th century. At that time, many scientists showed that bidirectional exchange and retention of intact cells, as well as non-cellular material, occurs between parents and their children, grandparents, and siblings. With the subsequent evolution of technology from histology to increasingly sophisticated techniques of molecular biology, documentation of microchimerism has been validated in both humans and animals with hemochorial placentation. The old concept that we, as individuals, consist of only our own cells is no longer true. We are all mosaics that contain cells, cell-free nucleic acids and extracellular vesicles from multiple family members. What we don’t know, however, is to what extent this non-self material affects evolution, pregnancy success, transplant acceptance, repair of disease, and development of the fetal immune system from a functional perspective. Further, the decades-long retention of fetal cells in maternal organs is being addressed in a pre-conference symposium focused on the ethical considerations of microchimerism and reproductive experiences. Microchimerism has attracted the interest of a multi-disciplinary group of scientists and physicians, and we are grateful that many of the established and early career scientists are with us today to address the critical questions in the field moving forward.
MICROCHIMERISM IN AUTOIMMUNITY AND ALLOIMMUNITY OVER TIME
Lee Nelson 1,2
1 Department of Medicine, University of Washington, Seattle, WA, USA
2Translational Science and Therapeutics Fred Hutchinson Cancer Center
Naturally acquired microchimerism (Mc) is creatively pleotropic and protean with beneficial and potentially detrimental consequences for an individual’s health. Mc creates a venue for forward, reverse, and horizontal inheritance, with long-term persistence after bi-directional maternal-fetal exchange, exchange between twins, and among littermates in dogs and mice. HLA molecules function in multiple key roles to maintain an individual’s health, discerning harmful infections, preventing harmful autoimmunity, and maintaining healthy alloimmunity. While mechanisms by which HLA molecules predispose or protect from an autoimmune disease are not fully understood, it is clear that age matters. The same HLA molecule can even predispose to different diseases at different lifespan times. Mc is of special interest because it is most often only HLA-haploidentical with the hosting individual. Mc is also time-dependent with potentially different impact as an individual and the Mc age (and whether Mc was acquired in utero or in adult life). Women acquire Mc during pregnancy and a woman’s reproductive history clearly impacts numerous aspects of subsequent health, including autoimmunity, cardiovascular disease, and risk of some malignancies. An example of the time-dependence of parity is reduction of rheumatoid arthritis risk with protection diminishing as time elapses from a birth, vanishing by ten years. Time elapsed from a birth is also a factor in protection against some malignancies such as breast cancer. At present, Mc in healthy alloimmunity against malignancies is relatively underexplored, but clear benefit of donor-recipient HLA-disparity is well established in the setting of hematopoietic cell transplantation (HCT). Further intriguing is decreased leukemia relapse rate after HCT when cord blood is the donor product, implicating HLA-mismatched maternal Mc in cord blood. Looking to the future, Mc and HLA-relationships are therefore of particular interest to understand the interface of autoimmunity and healthy alloimmunity and for development of novel preventative and therapeutic interventions.
Acknowledgements
The author’s work was supported by NIH grants HL-117737, AI-45659, the Washington Women’s Foundation and the Wong Foundation.
Competing interests
JLN is a co-founder of Chimerocyte, Inc. that develops highly sensitive chimerism analysis technologies. Chimerocyte, Inc. had no role in funding this research.