Why Doesn’t a Mother Reject Her Fetus?

Immune Activation Early in Pregnancy: Trouble Down the Road?

Silver RM.

Am J Obstet Gynecol 2008;199:327–328..

Complement Activation Fragment Bb in Early Pregnancy and Spontaneous Preterm Birth

Lynch AM, Gibbs RS, Murphy JR, et al.

Am J Obstet Gynecol 2008;199:354.e1–354.e8.

It is a wonder of pregnancy that the fetus is not rejected by the mother’s immune system. A fetus must have some favored status that allows maternal tolerance, but the exact modifications of her immune responses have so far defied definition. It is clear that when the tolerance process goes awry, a spectrum of disorders results, such as miscarriage, fetal demise, preeclampsia, and preterm labor. It is postulated that deficient tolerance in early pregnancy leads to adverse outcomes months later.

The activation of the immune response or its suppression is being unraveled by the exploration of various pathways, many of which involve mediators of inflammatory mechanisms. One that is yielding intriguing results is the complement activation mechanism. Silver indicates that complement activation has been implicated in a number of autoimmune processes including lupus, rheumatoid arthritis, asthma, and various renal disorders.

In pregnancy, complement activation seems to have a key role in fetal loss associated with antiphospholipid syndrome. Complement activation or inhibition may be crucial in the treatment of the syndrome or in unexplained recurrent pregnancy losses.

Research by Lynch and colleagues now suggests that complement activation (or failure of its suppression) in early gestation leads to a greater risk of preterm labor downstream. Through a complex series of steps that mediate inflammatory events, enzymes trigger the body’s normal protective functions and these have been pursued as infective or inflammatory causes of preterm labor. The latest work suggests it is not infection starting the process, but early abnormal complement activation. By measuring serum levels of one of the complement activation fragments (called Bb), the researchers were able to show an association between abnormally high levels and spontaneous preterm delivery prior to 34 weeks of gestation.

It is early days, but a marker of inflammatory action that could predict preterm labor would be an important first step in management protocols. Watch for Bb!