Estrogens in Pregnancy and Systemic Lupus Erythematosus

Abstract

Successful pregnancy depends on an adaptation of the maternal immune system that becomes tolerant to fetal antigens of paternal origin. The altered immune regulation induced by pregnancy occurs predominantly at the maternal-fetal interface, but it has also been observed in the maternal circulation. Th1/Th2 shift is one of the most important immunologic changes during gestation. It is due to the progressive increase of estrogens, which reach peak level in the third trimester of pregnancy. At these high levels, estrogens suppress the Th1-mediated responses and stimulate Th2-mediated immunologic responses. For this reason Th1-mediated diseases, such as rheumatoid arthritis, tend to improve, while Th2-mediated diseases, such as systemic lupus erythematosus (SLE) tend to worsen during pregnancy. However, in some recent studies SLE flare-ups were less frequently observed in the third trimester of gestation in comparison to the second trimester and postpartum period. These data are apparently in contrast to the Th2 immune-response polarization expected during pregnancy due to the progressive increase of estrogens. Some further data suggest that in SLE patients estradiol serum levels are surprisingly lower than expected during the third trimester of pregnancy, probably due to a placental compromise. This occurrence could lead to a lower-than-expected increase of IL-6, accounting for the low humoral immune response and the low disease activity observed in the third trimester of pregnancy in such patients.

Effector T cells in rheumatoid arthritis: Lessons from animal models

“…Additionally, under T H 2-mediated conditions such as atopic disorders and during pregnancy, RA symptoms seem to improve [157,158]. There is evidence that the increase of estrogen during pregnancy leads to T H 2 polarization and systemic IL-4 production; therefore the prevalence of RA in females after menopause may in part be due to a loss of T H 2 protection after the drop in estrogen levels [159]. Therefore, most animal models support the concept that in patients with RA, T H 2 responses seem to have a regulatory function in disease.…”

Fókuszban a szöveti biomarkerek. Az ösztrogének mint a szövetspecifikus immunválasz és autoimmunitás modulálásának kulcsszereplői

“…A terhesség során ösztrogén hatására a Th1/Th2 arány Th2 irányba tolódik el [12]. Az ösztrogén T helper vá-laszt befolyásoló hatása dózisfüggő: magas dózisban a Th2-választ serkenti, az alacsony dózisú ösztrogén viszont stimulálja a Th1-választ, fokozza az antigén-specifi kus CD4+ T-sejt-választ és elősegíti az IFN-gammatermelő sejtek keletkezését [4].…”

Estrogen and Autoimmune Disease

“…In the SLE patient, excessive Th2 responses could lead to increased production of autoantibodies and activated disease [16]. This theory has been brought into question [17] based upon a study in which estrogen concentrations did not increase during the second and third trimesters of lupus pregnancies. The abnormal response was thought to result from damage to the placenta or abnormal steroid metabolism in the placenta.…”