• Anti-phospholipid;
  • intrauterine growth regardation;
  • pre-eclampsia autoantibody;
  • cardiolipin

ABSTRACT: Abnormal autoimmune function has been associated with reproductive failure for decades. In fact, all medical conditions historically associated with pregnancy loss (and on occasion infertility) are now recognized to have an autoimmune etiology. It is therefore quite surprising that only less than a decade ago a correlation between the presence of abnormal autoantibodies and pregnancy loss was reported for the first time. Since reproductive failure, similar to other abnormal autoimmune states, is not a monoclonal event, we have established that affected patients demonstrate polyclonal autoantibody abnormalities including a variety of nonorganospecific as well as organspecific autoantibody groupings. For example, patients with repeated pregnancy loss will exhibit abnormal levels of anti-phospholipid antibodies (PA).

In normal pregnancy natural autoantibodies do not follow the standard immunoglobulin (Ig) pattern, characterized by a decrease in levels despite a probably mild increase in production, which is excessively compensated by the vasodilatation of pregnancy. PA, especially, demonstrate a mild increase during pregnancy, though levels only in the peripartal period may reach abnormally high titers (in comparison to nonpregnant controls). This dichotomy between total Ig and natural autoantibodies is interesting since it suggests that autoantibodies may be under distinct control. In fact, we have suggested that this observed elevation of autoantibodies may be the result of an antigenic stimulus by self-like antigen, represented by the maternal growth of the parasitic fetus.

In abnormal pregnancies, especially those associated with maternal hypertension and fetal growth retardation (IUGR), autoantibody levels do reach highly abnormal levels. We have reported that in both of these conditions significant abnormalities especially in IgG-PA can be detected, which stand in direct correlation with severity of disease (though autoimmune hemolytic anemia (AHA) can also be found). This is an interesting observation because both of these conditions have been associated with an imbalance between thromboxane and prostacyclin in favor of the platelet aggregating and vasoconstrictive thromboxane. This is exactly the imbalance reported in women with habitual abortions, which is assumed to be PA-induced. Aspirin, recently widely reported as being successful in the prevention of pregnancy-induced hypertension (PIH) and IUGR, has also been recommended as treatment for habitual aborters. Lastly, habitual aborters who are successfully treated and reach viability in a subsequent pregnancy, experience a highly increased incidence of PIH and IUGR. All of these observations strongly suggest that PIH, IUGR, and repeated pregnancy loss may have a common pathophysiology. It is tempting to speculate that it is autoantibody—and especially PA—related.