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Immunization against α IIb β 3 and α v β 3 in Glanzmann thrombasthenia patients carrying the French Gypsy mutation
Ist Teil von
Journal of thrombosis and haemostasis, 2021-01, Vol.19 (1), p.255
Ort / Verlag
England
Erscheinungsjahr
2021
Link zum Volltext
Quelle
Electronic Journals Library
Beschreibungen/Notizen
Essentials The c.1544+1G>A mutation was identified in Gypsy Glanzmann thrombasthenia (GT) patients. Gypsy GT patients express normal α
β
carrying HPA-1b epitopes. To demonstrate HPA-1a alloimmunization by modified antigen capture assays. Gypsy GT patients could develop anti-HPA-1a alloantibodies against β
and α
β
. ABSTRACT: Background Glanzmann thrombasthenia (GT) is a rare bleeding disorder caused by the absence or the dysfunction of the platelet α
β
integrin. A founder mutation in the ITGA2B gene was previously identified in French Gypsy patients. Interestingly, this mutation was strongly linked to the human platelet antigen-1b (HPA-1b). The HPA-1bb Gypsy patients are at risk of isoimmunization against α
β
, as this complex is not expressed at their platelet surface. Tentatively, they would, however, not have an increased risk of developing anti-HPA-1a alloantibodies by exposure of α
β
on platelets from random platelet transfusions. However, the β
chain can also associate with the α
subunit expressed at the platelet surface. Because Gypsy GT patients express normal α
β
carrying HPA-1b epitopes, these patients might develop anti-HPA-1a alloantibodies reacting with α
β
and/or β
. Objectives/Patients/Methods To demonstrate this hypothesis, sera from HPA-1bb (n = 5) and HPA-1ab (n = 1) Gypsy GT patients were investigated by modified antigen capture assay using platelets or stable transfected cells. Furthermore, stable transfected cells expressing either α
β
or α
β3 together with soluble monomeric chimeric β
(as absorbent) were used to differentiate anti-β
and anti-α
β
reactivity. Results Only HPA-1bb patients developed alloantibodies reacting with HPA-1a cells. Further analysis showed that HPA-1bb patients developed anti-HPA-1a alloantibodies reacting with β
and/or α
β
. Conclusion In this study, we found that HPA-1bb patients who failed to express α
β
on the platelet surface can develop alloantibodies against HPA-1a reacting with β
as well as α
β
. This is of particular importance as anti-HPA-1a alloantibodies might cause fetal neonatal alloimmune thrombocytopenia and/or platelet transfusion refractoriness.