Abby C Eblen

Alterations in humoral immune responses associated with recurrent pregnancy loss

OBJECTIVE To investigate the reactivity of maternal antibodies with endometrium-derived antigens and to correlate their association with recurrent pregnancy loss (RPL). DESIGN Prevalence study. SETTING Academic research center. PATIENT(S) Nulliparous women (n = 10), women with RPL (n = 15), pregnant women (n = 8), and multiparous women with a normal obstetric history (n = 20). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Reactive antibodies were analyzed by Western immunoblot techniques and quantitated by densitometry. RESULT(S) Antibodies from women with RPL and multiparous women recognized antigens ranging from 10-120 kd on normal endometrium and endometrial tumors. Antibodies from most women with RPL (10/15) and from multiparous women (15/20) recognized 65-kd and 80-kd proteins in normal endometrium. Antibodies from women with RPL recognized 21-kd and 28-kd antigens (12/15 and 13/15, respectively) in endometrial tumors at a significantly greater rate (than did antibodies from multiparous women (5/20 and 8/20, respectively). Women with RPL had significantly lower levels of asymmetric IgG compared with controls. CONCLUSION(S) Recurrent pregnancy loss may be linked with the failure to elicit asymmetric IgG and a unique immunologic recognition of endometrial antigens.

Modulation of T-cell CD3-zeta chain expression during normal pregnancy.

The objectives of this study were to assess the modulation of T-cell CD3-zeta expression by factor(s) present in sera of pregnant women, to correlate this activity with markers of T-cell function associated with pregnancy, and to identify the presence of a circulating pregnancy-associated factor responsible for the suppression of CD3-zeta chain. The suppression of TcR/CD3-zeta expression on cultured T-lymphocytes (Jurkat cells) by sera and amniotic fluids from pregnant women was examined by Western immunoblots and quantitated by densitometry. This suppression was correlated with the induction of T-cell apoptosis and reduced production of IL-2. The serum component suppressing zeta expression was characterized by ultrafiltration and protease sensitivity. Incubation of Jurkat cells with sera obtained from women in the first trimester produced a slight, but not statistically significant, suppression of zeta expression; however, sera from pregnant women in the second and third trimesters and amniotic fluids significantly suppressed zeta levels in a dose-dependent manner. The loss of zeta chain correlated with both reduced secretion of IL-2 and induction of lymphocyte apoptosis. Fractionation of sera by ultrafiltration demonstrated that the zeta chain suppressive factor was <5 kDa, and its trypsin-sensitivity suggests a proteinaceous moiety. Pregnancy is associated with a progressive suppression of cell-mediated immunity. These suppressed T-cell functions have been linked to Fas/Fas ligand-induced apoptosis and suppression of Th1 cytokines, including IL-2. We demonstrate that these pregnancy-associated events are mimicked by a factor(s) present in patient-derived fluids. Suppression of zeta expression appears to be due to a circulating low-molecular-weight protein that suppresses CD3-zeta in a concentration-dependent manner.

Modulation of T-cell CD3-zeta chain expression in early pregnancy.

PROBLEM: To assess the modulation of T‐cell CD3‐zeta chain expression by a factor in the sera of women, prior to egg retrieval and 14 days after an in vitro fertilization (IVF) and to delineate the mechanism of this modulation.