Thus, recent findings support the conclusion that both MMc and FMc can differentiate into somatic tissues. Therefore naturally acquired microchimerism from pregnancy could sometimes become a target for an immune response and/or could potentially contribute to tissue regeneration. If the former, new therapeutic options could block immune responses; if the latter microchimerism could potentially be exploited for therapeutic benefit in tissue regeneration.
Microchimerism in SLE
A strong rationale is provided for investigation of microchimerism in systemic lupus erythematosus (SLE) based on experimental models—especially MMc. A well-recognized murine model of SLE is created by the introduction of parental cells into non-irradiated F1 progeny and results in IgG antinuclear antibody production and fatal immune complex glomerulonephritis.20 Additionally, chronic graft-versus-host disease after allogeneic stem cell transplantation sometimes exhibits SLE-like features.
Although no study has tested for MMc in human SLE, an increased frequency of mother–child HLA class II sharing was found in a study of men with SLE.21 Male patients were selected to avoid potential confounding in women due to FMc. A few studies have tested for male DNA as a measure of FMc in peripheral blood from SLE patients.22 In a recent report male cells were found significantly more often in kidney biopsies from 49 women with lupus nephritis than control kidneys.23 Chimeric T lymphocytes as well as cells with stem cell markers were identified in some lupus nephritis specimens. Thus, experimental models and initial studies indicate further investigation is needed of microchimerism in SLE.
Summary
Bi-directional cell trafficking occurs between a mother and fetus during pregnancy. Many years after the physical union of mother and child is severed, MMc is found in her progeny and FMc is found in women who were previously pregnant. In some autoimmune rheumatologic diseases, microchimerism may be advantageous; in others, detrimental. On the beneficial side, it is likely that genetically disparate FMc contributes to the pregnancy-induced amelioration of RA. On the detrimental side, persisting FMc has been implicated in SSc pathogenesis. While only women are subject to FMc, all individuals are subject to MMc—including men, children, and nulligravid women. MMc is acquired during fetal life when the immune system is under development, whereas when FMc is acquired the immune system is mature. Therefore effects may differ.
Studies of MMc suggest that maternal effector cells could be involved in juvenile myositis and that maternal cardiac myocytes could be the immunologic targets in neonatal lupus syndrome. In addition to FMc and MMc, future studies must investigate other potential sources of naturally acquired microchimerism, such as microchimerism from an older sibling transferred via the maternal circulation or from twin–twin transfer in utero, including from an unrecognized twin lost early in gestation. Studies of rheumatologic autoimmune diseases are leading the way in this investigative frontier and generating new insights into the chimeric self in health and autoimmune disease as well as pointing the way to new possibilities in therapeutic approaches to autoimmune diseases.
