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Immunization against α IIb β 3 and α v β 3 in Glanzmann thrombasthenia patients carrying the French Gypsy mutation
Author(s) -
Fiore Mathieu,
Bayat Behnaz,
Phuangtham Roongaroon,
Blouin Laura,
Huguenin Yoann,
Bein Gregor,
Santoso Sentot
Publication year - 2021
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.15117
Subject(s) - glanzmann's thrombasthenia , thrombasthenia , medicine , immunization , mutation , platelet , immunology , genetics , platelet aggregation , biology , antibody , gene
Essentials The c.1544+1G>A mutation was identified in Gypsy Glanzmann thrombasthenia (GT) patients. Gypsy GT patients express normal α v β 3 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 3 and α v β 3 .Abstract Background Glanzmann thrombasthenia (GT) is a rare bleeding disorder caused by the absence or the dysfunction of the platelet α IIb β 3 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 IIb β 3 , 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 IIb β 3 on platelets from random platelet transfusions. However, the β 3 chain can also associate with the α v subunit expressed at the platelet surface. Because Gypsy GT patients express normal α v β 3 carrying HPA‐1b epitopes, these patients might develop anti‐HPA‐1a alloantibodies reacting with α v β 3 and/or β 3 . 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 IIb β 3 or α v β3 together with soluble monomeric chimeric β 3 (as absorbent) were used to differentiate anti‐β 3 and anti‐α v β 3 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 3 and/or α v β 3 . Conclusion In this study, we found that HPA‐1bb patients who failed to express α IIb β 3 on the platelet surface can develop alloantibodies against HPA‐1a reacting with β 3 as well as α v β 3 . This is of particular importance as anti‐HPA‐1a alloantibodies might cause fetal neonatal alloimmune thrombocytopenia and/or platelet transfusion refractoriness.