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Current Anti-HPA-1a Standard Antibodies React with the β3 Integrin Subunit but not with αIIbβ3 and αvβ3 Complexes.

Authors :
Bayat B
Traum A
Berghöfer H
Werth S
Zhu J
Bein G
Sachs UJ
Santoso S
Source :
Thrombosis and haemostasis [Thromb Haemost] 2019 Nov; Vol. 119 (11), pp. 1807-1815. Date of Electronic Publication: 2019 Oct 06.
Publication Year :
2019

Abstract

Background:  Fetal/neonatal alloimmune thrombocytopenia (FNAIT) results from maternal alloantibodies (abs) reacting with fetal platelets expressing paternal human platelet antigens (HPAs), mostly HPA-1a. Anti-HPA-1a abs, are the most frequent cause of severe thrombocytopenia and intracranial hemorrhage (ICH).<br />Objectives:  Titration of anti-HPA-1a in maternal serum using standard National Institute for Biological Standards and Control (NIBSC) 03/152 is one diagnostic approach to predict the severity of FNAIT. Recently, we found three anti-HPA-1a subtypes reacting with the β3 subunit independently or dependently from complexes with αIIb and αv. Endothelial cell-reactive anti-αvβ3 abs were found predominantly in cases with ICH. Our aim was to assess whether available standard material represents all anti-HPA-1a subtypes.<br />Materials and Methods:  In this study, anti-HPA-1a sera (NIBSC 03/152) and human monoclonal antibodies (moabs) against HPA-1a (moabs 26.4 and 813) were evaluated using transfected cell lines expressing αIIbβ3, αvβ3 or monomeric cβ3.<br />Results:  Flow cytometry analyses with well-characterized murine moabs recognizing αIIbβ3, αvβ3, or β3 alone demonstrated that AP3 reacts compound-independently, whereas compound-dependent moabs Gi5 and 23C6 reacted only with complexes. NIBSC 03/152, moabs 26.4, and 813 against HPA-1a reacted like AP3, same results were obtained with monomeric cβ3 in immunoblotting. Antigen capture assay targeting endothelial cells showed anti-HPA-1a reactivity disappearance after cβ3 beads adsorption. Furthermore, in contrast to anti-HPA-1a abs from ICH cases, none of NIBSC 03/152, 26.4, and 813 inhibited tube formation.<br />Conclusion:  These results suggest that current anti-HPA-1a standard material contains only the anti-β3 subtype. The absence of anti-αvβ3 makes NIBSC 03/152 less suitable as standard to predict the severity of FNAIT.<br />Competing Interests: None declared.<br /> (Georg Thieme Verlag KG Stuttgart · New York.)

Details

Language :
English
ISSN :
2567-689X
Volume :
119
Issue :
11
Database :
MEDLINE
Journal :
Thrombosis and haemostasis
Publication Type :
Academic Journal
Accession number :
31587244
Full Text :
https://doi.org/10.1055/s-0039-1696716