Proliferative responses to recall antigens are associated with pregnancy outcome in women with a history of recurrent spontaneous abortion.

Abstract

Maternal tolerance of the fetal hemiallograft suggests that immunomodulation occurs during gestation. Therefore, recurrent spontaneous abortion (RSA) may represent a failure of the immune changes that maintain pregnancy. We hypothesized that fertile women but not women with RSA may lose their immune responses to recall antigens when pregnant. This phenomenon has been seen in immunosuppressed transplant recipients and is associated with graft survival. Therefore, we evaluated proliferative responses to recall antigens in four groups of women: group 1, nonpregnant fertile women with no history of pregnancy loss and at least one prior healthy pregnancy, n ϭ 13; group 2, nonpregnant women with a history of three or more spontaneous abortions, n ϭ 28; group 3, healthy pregnant women between 6 and 9 wk of gestation without a history of prior pregnancy loss, n ϭ 15; and group 4, pregnant women between 6 and 9 wk of gestation, with a history of RSA, n ϭ 22. Proliferative responses of peripheral blood leukocytes to the recall antigens influenza and tetanus, alloantigens, and phytohemagglutinin were determined prospectively. Positive responses (stimulation index Ͼ 3) to recall antigens (a response to either influenza or tetanus was considered positive) were as follows: group 1 (nonpregnant fertile women), 11/13 (85%); group 2 (nonpregnant RSA women), 24 / 28 (86%); group 3 (pregnant fertile women), 4/15 (27%) ( P Յ 0.007); and group 4 (pregnant RSA women), 13/22 (59%) ( P ϭ NS). In group 4, there was 100% fetal survival in the nine women who lost responsiveness to recall antigens; however, in the 13/22 patients who responded to recall antigens, 9/13 (69%) had a repeat spontaneous abortion. These findings suggest that immunosuppression, indirectly measured by proliferation to recall antigens, is necessary for early pregnancy maintenance. Furthermore, this approach may be useful for predicting pregnancy outcome for women with RSA and may provide a useful means for designing and monitoring therapies. ( J. Clin. Invest. 1997. 100:1330-1334.)

The Role of Pregnancy‐Specific Glycoprotein 1a (PSG1a) in Regulating the Innate and Adaptive Immune Response

“…Among several explanations for the acceptance of the fetus, the one that suggests that the maternal immune system is suppressed or modified has been the subject of many studies. In agreement, several reports have demonstrated that during the normal pregnancy, a state of systemic suppression of the maternal immune system seems to be present . However, except for certain pathogens with defined predilection for prenatal infection, in general pregnant women are not significantly more susceptible to infections than non‐pregnant …”

Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunologic Perspectives

“…These peripheral and local changes could be the result of the direct action of progesterone on peripheral and uNK cells through nongenomic pathways or indirect effects on NK cells through support of a Th2 cytokine environment. It is known that proliferative responses of PBMC to recall antigens such as influenza A and tetanus as well as to alloantigens are significantly decreased in healthy women in early pregnancy compared with the nonpregnant state (159). These changes occur in an immune environment characterized by decreased levels of Th1 cytokines.…”

Immune mechanisms of childhood asthma

“…There is evidence both in murine and human studies that during pregnancy the maternal immune response is of the Th2 type, as Th1 type cell mediated immune responses are potentially harmful to the maintenance of pregnancy 65-68. Pregnant women have compromised cell mediated immunity,69 impaired lymphocyte proliferation,70 and loss of peripheral blood mononuclear cell (PBMC) proliferative responses to recall antigens 71…”