Indications of anti-HY immunity in recurrent placental abruption

Placental abruption is a potential life-threatening condition for both the fetus and the mother, being significantly more common in pregnancies with male fetuses. The pathogenesis of placental abruption remains unknown. However, some recent reports point toward a maternal immune response against the fetus as a possible mechanism. No data exist concerning special characteristics of patients suffering recurrent placental abruptions.

Identification of all patients with recurrent placental abruption in a retrospective review of 881 consecutive Caucasian women seen in our tertiary centre for recurrent pregnancy losses between 1986 and 2005. The HLA, DRB1, DRB3, 4, 5 and DQB1 genotypes of patients were compared with relevant controls.

Eight patients were identified with recurrent placental abruption. The patients had a total of 22 abruptions; 18 (82%) in which the fetus died. Seven patients (88%) had first-born boys, and 15 abruptions (68%) involved male fetuses. All patients with a first-born boy, except one, had HLA-class II alleles known to restrict CD4+ T-cell responses against male-specific minor histocompatibility (HY)-antigens (HLA-DRB1*15, HLA-DRB3*0301 and HLA-DQB1*05). Haplotypes with these HLA-alleles constituted 64% of the patients' haplotypes compared to 28% of those of the controls (p=0.009). Furthermore, 43% of the patients were homozygous for these haplotypes compared to 5% of controls (p=0.023).

We have found that recurrent placental abruption is exclusively almost preceded by the birth of a boy and the majority of patients have HLA-class II known to restrict CD4 T-cell reactions against HY-antigens. This indicates that maternal immunological responses against HY-antigens play a role in recurrent placental abruption.