Specific maternal antibodies against human platelet antigen 1a (HPA-1a) may contribute to the development of fetal and neonatal alloimmune thrombocytopenia (FNAIT), according to a study abstract to be presented at the 67th American Society of Hematology Annual Meeting and Exposition.
Most cases of FNAIT are caused by anti-HPA-1a antibodies, the authors explained. However, many different antibodies fall into this category, and current tests for the disease typically do not fully capture this wide variation.
“Identifying maternal antibodies with pathogenic potential is critical to improving risk stratification and guiding individualized management strategies,” the researchers wrote.
The study investigated five different HPA-1a antibodies: 26.4, M-204, D-204, B2G1 and SZ21. To do this, the authors applied each of the antibodies to mouse and human platelets that were positive for HPA-1a.
Read more about FNAIT causes and risk factors
All of the antibodies promoted the aggregation of platelets in the presence of thrombin, an enzyme that encourages blood clotting. Without any thrombin, on the other hand, only M-204 caused aggregation of human platelets. Further investigation revealed that M-204 only affected human platelets due to the presence of a receptor protein called FcγRIIa, which is not found on mouse platelets.
Inhibiting FcγRIIa reversed the effect of M-204, supporting the mechanistic role of this receptor. M-204 also increased the production of P-selectin, another molecule that helps platelets stick to one another.
It is already known that anti-HPA-1a antibodies mark fetal platelets for destruction through a process known as opsonization. This study advances our understanding of the development of FNAIT by identifying an additional mechanism that may impact disease severity.
“These findings define a previously unrecognized, functionally distinct subset of antiHPA-1a antibodies capable of activating platelets via FcγRIIa,” the authors concluded. “This work may support development of function-based assays to enhance risk stratification in affected pregnancies.”
Sign up here to get the latest news, perspectives, and information about FNAIT sent directly to your inbox. Registration is free and only takes a minute.
