A recent study published in Frontiers of Immunology found that while anti-human leukocyte antigen (HLA) antibodies may trigger mild thrombocytopenia, their ability to cause fetal and neonatal alloimmune thrombocytopenia (FNAIT) is still uncertain.
What is thrombocytopenia?
Thrombocytopenia in fetal and neonatal alloimmune thrombocytopenia (FNAIT) refers to an abnormally low number of platelets in the fetus or newborn as a result of an immune reaction. This occurs when the mother’s immune system produces antibodies that target the fetal platelets, typically due to a mismatch in human platelet antigens (HPAs) between the mother and fetus. The maternal antibodies cross the placenta and attack the fetal platelets, leading to their destruction.
FNAIT is usually caused by anti-human platelet antigen (HPA) antibodies. In Caucasian populations, for example, anti-HPA-1a antibodies cause most cases of FNAIT.
Although it has been suggested that anti-HLA antibodies may be implicated in rare cases of FNAIT, the evidence is conflicting. Studies have shown, though, that anti-HLA antibodies are common in patients who do not respond to platelet transfusions, indicating a potential role in platelet function.
Read more about FNAIT causes and risk factors
The study analyzed anti-HLA antibodies in blood samples and a mouse model to determine why these antibodies typically lead to mild thrombocytopenia.
Findings revealed that anti-HLA antibodies bound to platelets at relatively low levels. However, they bound to monocytes, a type of cell that helps regulate immune function, at high levels.
In patients with FNAIT, monocytes play a key role in the disease process by engulfing and destroying platelets. To understand the impact of anti-HLA binding to monocytes, the researchers added these antibodies to platelets treated with anti-HPA antibodies.
They found that in these samples, the anti-HLA antibodies prevented platelet destruction from occurring. This implies that anti-HLA antibodies are somehow working to dampen the response of monocytes to anti-HPA antibodies.
Next, the authors treated mice with anti-HLA antibodies and observed mild levels of thrombocytopenia. When the mice were given a type of antibody known to attack platelets, on the other hand, they experienced more severe thrombocytopenia.
“Whether these findings can explain the controversial opinions regarding the role of anti-HLA class I antibodies in FNAIT remains unclear and needs to be further addressed,” the researchers concluded.
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