A new mechanism could help explain differences in the severity of fetal and neonatal alloimmune thrombocytopenia (FNAIT), according to a study published recently in Transfusion.
The mechanism involves an antibody that can directly activate platelets and cause them to clump together in laboratory experiments.
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FNAIT is caused by an immune reaction in which the mother’s antibodies attack the baby’s platelets. This can happen when the baby inherits a platelet antigen from the father that the mother does not have. Her immune system recognizes this surface marker as foreign and produces antibodies against it. These antibodies can cross the placenta and lead to the destruction of the baby’s platelets.
Researchers previously understood that higher concentrations of antibodies do not reliably predict more severe bleeding complications. Now, they want to understand why this happens. They hypothesized that antibodies targeting the same platelet antigen could have different effects on platelet activation and clumping.
They studied five antibodies and their effects on platelets and found one—M-204—that directly activated the platelets and caused them to clump together. M-204 acts by activating a receptor called FcγRIIa, located on the platelet surface.
The effect of M-204 depended on its concentration and the type of platelets tested. At higher concentrations, M-204 reduced clumping in platelets carrying only HPAHuman platelet antigen Proteins found on the surface of platelets. Incompatibility between maternal and fetal human platelet antigens can trigger FNAIT.-1a. Although the antibody still activated these platelets, it also blocked the connections needed for them to join together.
Read more about FNAIT causes and risk factors
Platelets carrying both HPA-1a and another form, HPA-1b, continued to clump because M-204 left the HPA-1b form available to make those connections.
The findings suggest “a potential mechanism contributing to variability in disease severity in FNAIT,” the authors wrote. However, the clinical significance remains unclear.
They propose studying samples from mothers of babies with different degrees of FNAIT severity to assess whether their antibodies activate platelets. Further experiments in mice could also help determine how this activity contributes to the disease.
