Pregnancy has both short-term effects and long-term consequences. For women who have an autoimmune disease and subsequently become pregnant, pregnancy can induce amelioration of the mother's disease, such as in rheumatoid arthritis, while exacerbating or having no effect on other autoimmune diseases like systemic lupus erythematosus. That pregnancy also leaves a long-term legacy has recently become apparent by the discovery that bi-directional cell trafficking results in persistence of fetal cells in the mother and of maternal cells in her offspring for decades after birth. The long-term persistence of a small number of cells (or DNA) from a genetically disparate individual is referred to as microchimerism. While microchimerism is common in healthy individuals and is likely to have health benefits, microchimerism has been implicated in some autoimmune diseases such as systemic sclerosis. In this paper, we will first discuss short-term effects of pregnancy on women with autoimmune disease. Pregnancy-associated changes will be reviewed for selected autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid disease. The pregnancy-induced amelioration of rheumatoid arthritis presents a window of opportunity for insights into both immunological mechanisms of fetal-maternal tolerance and pathogenic mechanisms in autoimmunity. A mechanistic hypothesis for the pregnancy-induced amelioration of rheumatoid arthritis will be described. We will then discuss the legacy of maternal-fetal cell transfer from the perspective of autoimmune diseases. Fetal and maternal microchimerism will be reviewed with a focus on systemic sclerosis (scleroderma), autoimmune thyroid disease, neonatal lupus and type I diabetes mellitus.Keywords autoimmune disease; pregnancy; microchimerism; systemic lupus erythematosus; rheumatoid arthritis
PREGNANCY IN WOMEN WITH PRE-EXISTING AUTOIMMUNE DISEASEAutoimmune disease may complicate pregnancy in many different ways adding to the immunologic challenges already faced by the mother. The maternal immune system must avoid rejecting a semi-allogeneic fetus, remain immunocompetent to fight infections, and clear abnormal cells (e.g. precancerous) that could be harmful to the mother or fetus. Symptoms of an autoimmune disease could improve, worsen, or remain unchanged when a et al. 1987) In contrast, only a weak association between SLE susceptibility and HLA-DRB1*15 or DRB1*03 has been found in specific ethnic groups; it has been suggested that these associations are instead related to genes in linkage disequilibrium (e.g. gene encoding tumor necrosis factor-alpha with HLA-DRB1*15). (Jacob et al. 1990;Vyse and Kotzin 1998) Sex hormones and the immunologic effects of pregnancy have been investigated in autoimmunity. The well-studied relationship between sex hormones and lupus-like disease in animal models suggests a contributory role for estrogen in disease exacerbation and possibly in disease susceptibility. SLE may occur more frequently in women who have ...