A recent study investigated the pattern of anti-HPAHuman platelet antigen Proteins found on the surface of platelets. Incompatibility between maternal and fetal human platelet antigens can trigger FNAIT.-3 antibody binding on the platelet surface in fetal and neonatal alloimmune thrombocytopenia (FNAIT). The researchers found that glycans, or sugar chains often attached to the surface of cells, including platelets, play a role in that binding, a discovery that could lead to better ways to diagnose the rare bleeding disorder.
In FNAITFetal and neonatal alloimmune thrombocytopenia A rare condition in which a mother’s immune system attacks fetal platelets, leading to dangerously low platelet levels before and/or after birth., the antibodies most often target human platelet antigenHuman platelet antigen Proteins found on the surface of platelets. Incompatibility between maternal and fetal human platelet antigens can trigger FNAIT.-1a (HPA-1a), but antibodies against other HPAs can cause the condition too. This study focused on one of them, HPA-3, which sits on a platelet protein called glycoprotein IIb (GPIIb). HPA-3 comes in two slightly different forms, HPA-3a and HPA-3b, that differ by a single building block — one amino acid — at one position on the protein. Anti-HPA-3 antibodies are known to be difficult to detect with the tests used in clinics today.
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The team collected 11 plasma samples, all containing anti-HPA-3 antibodies, from patients with FNAIT and other related thrombocytopeniaThrombocytopenia A platelet count that is lower than normal. disorders. They also treated purified GPIIb proteins, derived from human platelets, with different enzymes that break the bond attaching glycans to the protein, then checked whether the anti-HPA-3 antibodies from patients’ samples could still bind.
Glycans attach to proteins in two main ways, known as N-linked (via a nitrogen atom) and O-linked (via an oxygen atom). When the researchers removed the N-linked sugars, the antibodies bound as before, but removing the O-linked sugars weakened the binding.
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Furthermore, when they treated the samples with enzymes to remove neuraminic acid, which caps the O-linked glycans near the HPA-3 site, binding sharply decreased, showing that anti-HPA-3 antibodies depend on neuraminic acid for binding.
Neuraminic acid is a form of sialic acid that is frequently bound to various cells, including platelets; in addition to its role in anti-HPA-3 antibody binding, it has been studied for its involvement in platelet count regulation.
“Understanding the epitopes that anti-HPA-3 antibodies bind to is essential for future development of improved FNAIT diagnostics,” authors wrote.
