Maternal Anti-HPA-1a Antibodies Increase Endothelial Cell Apoptosis and Permeability

Intracranial hemorrhage (ICH) associated with fetal/neonatal alloimmune thrombocytopenia (FNAIT) is attributed mainly to endothelial damage caused by binding of maternal anti-HPA-1a antibodies to the alpha v beta 3 integrin on endothelial cells (ECs). We examined the effect of anti-HPA-1a antibodies on EC function using 2 EC lines from different vascular beds, HMVEC of dermal origin and hCMEC/D3 of cerebral origin. Anti-HPA-1a sera significantly increased apoptosis in both HMVEC and hCMEC/D3 cells and permeability in hCMEC/D3 cells only. This increase in both apoptosis and permeability was significantly inhibited by a monoclonal anti-beta 3 antibody (SZ21) binding to the HPA-1a epitope. Our results indicate that (1) maternal anti-HPA-1a antibodies impair EC function by increasing apoptosis and permeability and (2) ECs from different vascular beds vary in their susceptibility to pathological effects elicited by maternal anti-HPA-1a antibodies on EC permeability. Examination of maternal anti-HPA-1a antibodies for their effect on EC permeability may predict potential ICH associated with FNAIT.

Automated summary

Maternal anti-HPA-1a antibodies impair endothelial cell function by increasing apoptosis and permeability, with endothelial cells from different vascular beds showing varying susceptibility to these pathological effects elicited by the antibodies. Examination of the effect of maternal anti-HPA-1a antibodies on endothelial cell permeability may predict potential intracranial hemorrhage associated with fetal/neonatal alloimmune thrombocytopenia.