The alloantibodies are directed against fetal plateletspecific antigens which are inherited from the father. The most widespread human platelet antigens accountable for the maternal immunisation within the Caucasian populations are HPA1 and HPA5 . An growing variety of private or rare HPAs related to FNAIT have already been reported during the last two decades. Meanwhile, 15 lowfrequency HPAs happen to be assigned. The majority of them reside on the ?IIb?three integrin , a single resides on glycoprotein GPIb? and two on the ?two?1 integrin . The ?IIb?three integrin is the big integral platelet glycoprotein which functions as a receptor for divalent fibrinogen, multivalent von Willebrand factor and also other ligands similar to vitronectin, fibronectin and thrombospondin. Ligand binding to ?IIb?3 integrin is controlled by insideout signals that modulate receptor conformation and clustering.
In turn, pathway inhibitor ligand binding triggers outsidein signals by way of ?IIb?3 . Crystal structure analysis revealed a complex domain structure that rearranges when the integrin switches from a resting to an active type . The ?IIb subunit consists of an aminoterminal ?propeller domain followed by a thigh domain and two calf domains. The ?three subunit has eight domains: an aminoterminal PSI domain, an Iglike hybrid domain that contains the ligandbinding ?Ahybrid domain, 4 EGFlike domains, as well as the ?tail domain. By the identification of these domains, point mutations accountable for HPAs may very well be localised precisely. No preferential domain was observed for HPAs, and all HPA related polymorphisms on GP IIb/IIIa described so far didn’t impair the receptor function.
In this study, we describe a case of FNAIT brought on by maternal alloimmunisation against a previously unreported, low frequency polymorphism on the ?three integrin subunit, termed Seca. This mutation is situated Chondroitin inside the EGF4 domain and alters the adhesion of ?IIb?3 to fibrinogen. Hence, the Seca alloantigen represents the initial lowfrequency polymorphism on ?three integrin which influences the receptor?s function. A 35yearold female having a history of miscarriages at gestational weeks 10 and 21, respectively, received dalteparin in the course of her third pregnancy. She delivered a fullterm boy within the 39th week of gestation with facial petechiae and cephalic haematoma, but no intracranial bleeding. Neonatal platelet count was 25 G/l. An initial therapy with intravenous immunoglobulins resulted inside a fast raise of the platelet count , and also the newborn was discharged devoid of any signs of sequelae.
While antibody testing in MAIPA making use of random donor platelets revealed unfavorable outcomes, a crossmatch analysis involving maternal serum and paternal platelets in a glycoproteinspecific assay showed constructive reactions with ?IIb?three, indicating an alloimmunisation against a new lowfrequency antigen residing on the ?IIb?three heterodimer.
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