J. Lee

Nelson

MD

 

Education & Training: 

MD, University of California, Davis, CA (1977)

Internship, Family Medicine Spokane, Spokane, WA (1977-1978)

Residency, Internal Medicine, University of California, Davis, CA (1978-1981)

Fellowship in Rheumatology, University of Washington, Seattle, W (1981-1983)

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.

PubMed: 

PubMed Bibliography

Publications: 

SELECTED more recent publications:

Kanaan SB, Delaney C, Milano F, Scaradavou A, van Besien K, Allen JA, Sensoy O, Forsyth A, Kahn E, Cousin E, Cox ER, Lambert NC, Nelson JL.   Mother of the cord blood donor in patients post-transplantation and patient outcome. Bone Marrow Transplant 56(5):1090-1098, 2021.

Kanaan SB, Sensoy O, Yan Z, Gadi VK, Richardson ML, Nelson JL. Immunogenicity of a rheumatoid arthritis protective sequence when acquired through microchimerism. Proceedings of the National Academy of Sciences USA 116(39):19600-19608, 2019.

Kanaan SB, Gammill HS, Harrington WE, De Rosa SC, Stevenson PA, Forsyth AM, Allen J, Delaney CS, Nelson JL. Maternal microchimerism is prevalent in cord blood in memory T cells and other cell subsets, and persists post-transplant. OncoImmunology 6(5):e1311436, 2017.

Harrington WE, Kanaan SB, Muehlenbachs A, Morrison R, Stevenson PA, Fried M, Duffy DE, Nelson JL. Maternal microchimerism predicts increased infection but decreased disease due to P. falciparum during early childhood. J Infectious Dis, 215(9):1445-51, 2017.

Gentil CA, Gammill HS, Luu CT, Mayes MD, Furst DE, Nelson JL.  Characterization of HLA-DRβ1 third hypervariable region amino acid sequence according to charge and parental inheritance in systemic sclerosis, Arthritis Res Therapy 19(1):46. doi: 10.1186/s13075-017-1253-9, 2017.

Stevens AM, Kanaan SB, Torok KS, Medsger TA, Mayes MD, Reveille JD, Klein-Gitelman M, Reed AM, Lee T, Li SC, Henstorf G, Luu C, Aydelotte T, Nelson JL. HLA- DRB1, DQA1 and DQB1 in juvenile-onset systemic sclerosis. Arthritis Rheum 68(11):2772-77, 2016.

Nelson JL, Lambert NC. Forward and reverse inheritance - the yin and the yang.  Nat Rev Rheumatol 13(7):396-7, 2017.

SELECTED earlier publications:

Nelson JL.  The Otherness of Self: Microchimerism in health and disease.  Trends in Immunology 33(8):421-7, 2012. 

Gammill HS, Adams Waldorf KM Aydelotte, TM, Lucas J, Leisenring WM, Lambert NC, Nelson JL. Pregnancy, microchimerism and the maternal grandmother. PLoS One, 6(8):e24101, 2011.

Yan Z, Gadi VK, Aydelotte TM, Guthrie KG, Nelson JL.  Acquisition of the rheumatoid arthritis HLA shared epitope through naturally acquired microchimerism. Arthritis Rheum 63(3):640-4, 2011.

Nelson JL.  Your cells are my cells.  Scientific American 298(2):64-71, 2008.

Nelson JL, Gillespie KM, Lambert NC, Stevens AM, Loubiere LS, Rutledge JC, Leisenring WM, Erickson TD, Yan Z, Mullarkey ME, Boespflug ND, Bingley PJ, Gale EAM.  Maternal microchimerism in peripheral blood in type 1 diabetes and pancreatic islet b cell microchimerism.  Proc Natl Acad Sci USA 104(5):1637-42, 2007.

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.

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 104:41-47, 1999.

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.

Nelson JL, Hughes K, Smith A, Nisperos B, Branchaud A, Hansen JA.  Maternal-fetal disparity in HLA class II alloantigens and the pregnancy-induced amelioration of rheumatoid arthritis. N Engl J Med 329:466-71, 1993.