What can cause an increase in maternal titer during pregnancy even if the fetus is negative?

An increase in maternal titer during pregnancy, even when the fetus is negative, can often be attributed to the amnestic response. This phenomenon occurs when the mother’s immune system has been previously sensitized to a particular antigen, perhaps from a previous pregnancy or exposure, leading to a rapid increase in antibody production upon re-exposure to that antigen during the current pregnancy.

The amnestic response is crucial in maternal-fetal medicine because it explains why maternal antibody levels can rise in cases where the fetus does not express the corresponding paternal antigen. Therefore, even if the fetus is negative for a specific antigen, the mother's immune system can still react more robustly due to this prior sensitization, enhancing antibody titers.

Other options don't provide the same explanation. For instance, heterozygosity for paternal antigen involves the genetic inheritance from the father that may not directly relate to maternal titer increases. Genetic mutation refers to changes in the genome that would not typically affect the pregnancy's immunological landscape in such a specific manner. Infection can affect maternal immunology, but it tends to not specifically correlate with an increase in titer in the absence of fetal antigen expression as clearly as the amnestic response does. Thus, the amnestic response is