Long-term fetal microchimerism in peripheral blood mononuclear cell subsets in healthy women and women with scleroderma

Fetal CD34(+) CD38(+) cells have recently been found to persist in maternal peripheral blood for many years after pregnancy. CD34(+) CD38(+) cells are progenitor cells that can differentiate into mature immune-competent cells . We asked whether long-term fetal microchimerism occurs in T lymphocyte, B lymphocyte, monocyte, and natural-killer cell populations of previously pr egnant women. We targeted women with sons and used polymerase chain reactio n for a Y-chromosome-specific sequence to test DNA extracted from periphera l blood mononuclear cells (PBMC) and from CD3, CD19, CD14, and CD56/16 sort ed subsets. We also asked whether persistent microchimerism might contribut e to subsequent autoimmune disease in the mother and included women with th e autoimmune disease scleroderma. Scleroderma has a peak incidence in women after childbearing years and has clinical similarities to chronic graft-ve rsus-host disease that occurs after allogeneic hematopoietic stem-cell tran splantation. known to involve chimerism. Sixty-eight parous women were stud ied for male DNA in PBMC and 20 for PBMC subsets. Microchimerism was found in PBMC from 33% (16 of 48) of healthy women and 60% (12 of 20) women with scleroderma, P = .046. Microchimerism was found in some women in CD3, CD19. CD14. and CD56/16 subsets including up to 38 years after pregnancy. Microc himerism in PBMC subsets was not appreciably more frequent in scleroderma p atients than in healthy controls. Overall, microchimerism was found in CD3, CD19, and CD14 subsets in approximately one third of women and in CD56/16 in one half of women. HLA typing of mothers and sons indicated that HLA com patibility was not a requirement for persistent microchimerism in PBMC subs ets. Fetal microchimerism in the face of HLA disparity implies that specifi c maternal immunoregulatory pathways exist that permit persistence but prev ent effector function of these cells in normal women. Although microchimeri sm in PBMC was more frequent in women with scleroderma than healthy control s additional studies will be necessary to determine whether microchimerism plays a role in the pathogenesis of this or other autoimmune diseases. (C) 1999 by The American Society of Hematology.