Back to Search
Start Over
Current Anti-HPA-1a Standard Antibodies React with the β3 Integrin Subunit but not with αIIbβ3 and αvβ3 Complexes.
- 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.)
- Subjects :
- Endothelial Cells immunology
HEK293 Cells
Humans
Isoantibodies blood
Neovascularization, Physiologic
Predictive Value of Tests
Reproducibility of Results
Severity of Illness Index
Thrombocytopenia, Neonatal Alloimmune blood
Thrombocytopenia, Neonatal Alloimmune immunology
Antibodies, Monoclonal immunology
Antibody Specificity
Antigens, Human Platelet immunology
Immunologic Tests
Integrin alphaVbeta3 immunology
Integrin beta3 immunology
Isoantibodies immunology
Platelet Glycoprotein GPIIb-IIIa Complex immunology
Thrombocytopenia, Neonatal Alloimmune diagnosis
Subjects
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