4th Annual BMRP Investigator Meeting - Abstract
Maternal Microchimerism in Inflammatory Bowel Disease
David L. Suskind1,a, Denice Kong2, Lee-Ann Baxter-Lowe2 and Marcus O. Muench3,b
1Department of Pediatrics, Children’s Hospital and Regional Medical Center and University of Washington (Seattle, Washington, U.S.A.); 2Department of Immunogenetics, University of San Francisco (San Francisco, California, U.S.A.); 3Blood Systems Research Institute (San Francisco, California, U.S.A)
Inflammatory bowel disease (IBD) shares many immunologic and clinical characteristics with graft versus host disease (GVHD), a disease caused by the transfer of allogeneic cells during bone marrow transplantation. In each, CD4+ T lymphocytes appear central in the development of enteropathy. CD4+ T cells recognize major histocompatibility complex (MHC) class II, which is increased in both. Additionally, adoptive transfer models in which allogeneic cells are transferred to a host animal have been shown to cause an IBD-like illness. Since maternal cells are known to enter the fetal circulation in pregnancies, we hypothesize that maternal engraftment in the fetus could result in immune sequela that could lead to IBD.
We initiated a prospective case control study involving assessment of human leukocyte antigens (HLA) in persons with IBD and controls, and their mothers. Using kinetic Polymerase Chain Reaction (kPCR), the presence and extent of maternal microchimerism in the tissues and blood samples from patients then was determined.
Maternal microchimerism was observed in six of the nine (67%) patients with IBD and in one of 11 in the control group (9%) (P=0.01). Microchimerism was found in the blood of one of the Crohn’s patients and in the tissue samples of six of the Crohn’s patients. In the Crohn’s patient with maternal microchimerism in the blood, 1.6 copies of maternal DNA was found per 2.5 x 104 copies of patient’s DNA. In the tissue samples of the Crohn’s patients with maternal microchimerism, microchimerism was found in a range of 0.06 to 1.0 copies of maternal DNA per 2.5 x 104copies of patient DNA. Currently, additional samples are being analyzed as well as functional studies, mixed leukocyte reaction and cytokine assays, which will examine the patient’s immune response to maternal antigen.
aPrincipal Investigator; bCo-investigator and Presenter