Division of Rheumatology
1959 NE Pacific St
Health Science Bldg BB561
Campus Box 356428
Seattle, WA 98195
J. Lee Nelson, M.D.
Professor of Medicine
Division of Rheumatology
Fred Hutchinson Cancer Research Center
1100 Fairview Ave N
Seattle, WA 98109-1024
Nelson Lab | Phone: 206-667-6840
EDUCATION AND TRAINING
CURRENT RESEARCH INTERESTS
Dr. Nelson’s research group investigates immunologic consequences of maternal-fetal exchange during pregnancy and the legacy that maternal-fetal exchange creates for both individuals years later. A mother’s cells persist in her children into adult life and cells of fetal origin remain in the mother decades later. “Microchimerism” refers to harboring a small number of cells (or DNA) that originated in a genetically different individual. Dr. Nelson’s multidisciplinary research group investigates microchimerism in autoimmune disease, infectious disease, cancer, and transplantation.
Early research by her group evaluated immunologic consequences of pregnancy in the setting of autoimmune disease. Women with rheumatoid arthritis often experience arthritis amelioration during pregnancy. The group found that fetal-maternal differences for particular molecules, called HLA class II, correlated with arthritis improvement during pregnancy. In a subsequent study the team directly identified fetal-specific DNA in maternal blood and showed that higher levels correlated with pregnancy-induced arthritis amelioration. These HLA molecules are also important in transplantation and must be well-matched for organ and bone marrow transplantation to be successful.
Some HLA “types” are associated with risk of specific diseases, while other HLA molecules are protective. The Nelson team found that women who themselves lacked HLA “risk” molecules could acquire disease risk through cells from pregnancy (microchimerism), a kind of “mini-gene transfer of pregnancy”. On the other hand they also found that if microchimerism was acquired that had “protective” HLA molecules, pregnancy could result in a vaccine-like protection against disease that persisted for many years.
The autoimmune disease systemic sclerosis (also called scleroderma) has striking similarities to a syndrome that can develop after hematopoietic cell transplantation called “graft-versus-host disease”. Reasoning that cells exchanged during pregnancy create a legacy that lasts for decades Dr. Nelson proposed that microchimerism plays a role in some autoimmune diseases and first reported the novel finding of greater fetal origin microchimerism in women with systemic sclerosis compared to healthy women. Moreover, in studies of neonatal lupus, a passively acquired autoimmune disease associated with serious congenital heart block, the team identified maternal microchimerism in the heart and found that most maternal cells were not simply blood cells but rather were cardiac muscle cells. They also found maternal cells in the pancreas that produced insulin. Her team and others have found that maternal cells are normally present in a variety of organs and increased in some diseases. Read more about her research...
CURRENT LABORATORY STUDIES
While work on microchimerism in autoimmune disease continues, the group has since become interested in much broader ways in which consequences of maternal-fetal exchange are likely to impact human health. Women who have given birth generally have reduced breast cancer risk, suggesting fetal origin microchimerism may be protective. Consistent with this idea, they found less fetal microchimerism in women with breast cancer, compared to those without.
The Nelson group also found that microchimerism from a woman’s own mother becomes less detected after the woman has had her own children, suggesting child-derived microchimerism can displace microchimerism from the ‘grandmother. They are interested in whether this type of “graft-versus-graft” effect is analogous to the observation in double cord blood transplantation that only one unit appears to “win out” over time. The group is currently investigating maternal microchimerism in recipients of cord blood transplantation as potentially giving a protective boost against recurrent leukemia in the recipient. They previously showed that microchimerism is present in products that are administered to patients during hematopoietic stem cell transplantation.
These findings are giving us important clues as to precisely how maternal-fetal microchimerism can impact human health, and may lead to strategies to predict and perhaps prevent a variety of different diseases.
RECENT REPRESENTATIVE PUBLICATIONS
Mittal A, Pachter L, Nelson JL, Kjærgaard H, Smed MK, Gildengorin VL, Zoffmann V, Hetland ML, Jewell NP, Olsen J, Jawaheer D. Pregnancy-Induced Changes in Systemic Gene Expression among Healthy Women and Women with Rheumatoid Arthritis. PLoS One. 2015 Dec 18;10(12):e0145204. doi: 10.1371/journal.pone.0145204. eCollection 2015. PMID: 26683605
Gammill, HG, Nelson JL. Naturally acquired microchimerism. Int J Dev Bio, 54:531-43, 2010. PMCID: In process.
Guthrie KA, Gammill HS, Madeleine MM, Dugowson CE, Nelson JL. Parity and HLA alleles in risk of rheumatoid arthritis. Chimerism. 2011 Jan;2(1):11-15.
Adams-Waldorf K, Gammill HS, Lucas J, Aydelotte TM, Leisenring W, Lambert NC, Nelson JL. Dynamic changes in fetal microchimerism in maternal peripheral blood mononuclear cells, CD4+ and CD8+ cells in normal pregnancy. Placenta, May 31, 2010. [Epub ahead of print.]
Radstake TRDJ, Gorlova O, Rueda B, Martin JE, Alizadeh B, Palomino-Morales R, Coenen M, Vonk M, Voskuyl A, Scheurweg A, Broen J, van Riel PLCM, Riemekasten G, Gay G, Gonzalez-Escribano M, Spanish Scleroderma Group, Gregersen P, Lee A, Wigley F, Hummers L, Nelson JL, Agarwal S, Assassi S, Gourh P, Tan F, Koeleman B, Arnett F, Martin J, Mayes M. Genome-wide association study in systemic sclerosis identifies novel susceptibility loci. Nature Genetics, Apr 11 2010. [Epub ahead of print].
Guthrie KA, Dugowson C, Voigt LF, Koepsell TD, Nelson JL. Does pregnancy provide vaccine-like protection against rheumatoid arthritis? Arthritis Rheum, Mar 22 2010. [Epub ahead of print.]
Nelson JL. Naturally acquired microchimerism: For better or for worse. Arthritis Rheum 60:5-7, 2009. PMCID: PMC2693961.
Stevens, AM, Hermes HM, Kiefer MM, Rutledge JC, Nelson JL. Chimeric Maternal cells with tissue-specific antigen expression and morphology are common in infant tissues. Pediatr Dev Pathol 12:337-46, 2009. PMCID: PMC2783488.
Adams KA, Nelson JL. Autoimmune disease during pregnancy and the microchimerism legacy of pregnancy. Immunol Invest 37:631-44, 2008. PMCID: PMC2709983.
Guthrie KG, Tishkevich NR, Nelson JL. Non-inherited maternal HLA alleles in susceptibility to familial rheumatoid arthritis. Ann Rheum Dis 68:107-9, 2009. PMCID: PMC2760537.