Maternal HLA Panel-Reactive Antibodies in Early Gestation Positively Correlate with Chronic Chorioamnionitis: Evidence in Support of the Chronic Nature of Maternal Anti-fetal Rejection

Problem Maternal tolerance of the fetus is essential for viviparity, yet anti-fetal rejection occurs in several pregnancy complications. Chronic chorioamnionitis is a feature of anti-fetal cellular rejection. There is a robust association between chronic chorioamnionitis and maternal seropositivity for anti-human leukocyte antigen (HLA) panel-reactive antibodies (PRA) at the time of delivery. This longitudinal study was performed to assess maternal HLA PRA status in early gestation and the temporal evolution of maternal HLA PRA in the context of chronic chorioamnionitis and, thereby, to determine whether HLA PRA during the course of pregnancy is useful for the detection of anti-fetal rejection. Method of study Maternal sera obtained before 16weeks of gestation and at delivery were analyzed for HLA PRA in cases with (N=100) and without (N=150) chronic chorioamnionitis. Results IgG (but not IgM) HLA class I and II PRA positivity at delivery was higher in cases with chronic chorioamnionitis than in those without chronic chorioamnionitis. IgG HLA class I PRA positivity before 16weeks of gestation was higher in cases with chronic chorioamnionitis than in those without (30.3 versus 13.3%; P=0.001). Positive conversion (negative HLA PRA before 16weeks of gestation but positive at delivery) of IgG HLA class I and II PRA was significantly associated with chronic chorioamnionitis. Fetal HLA class I antigen-specific antibodies were confirmed in 12 of 16 mothers tested who were sensitized to HLA class I antigens before 16weeks of gestation. Conclusion Positive maternal HLA PRA before 16weeks of gestation and the temporal evolution of maternal HLA PRA are associated with the presence of chronic chorioamnionitis at the time of delivery. Maternal IgG HLA PRA has the potential to be a monitoring tool of anti-fetal rejection. Furthermore, the findings herein indicate that subsets of fetuses are exposed to alloimmune HLA antibodies for months, especially in cases with chronic chorioamnionitis.