Prophylactic administration of HPA-1a-specific antibodies prevents fetal/neonatal alloimmune thrombocytopenia in mice. Blood 2022 Nov 17;140(20):2146-2153
Date
07/27/2022Pubmed ID
35881848Pubmed Central ID
PMC9837438DOI
10.1182/blood.2022015666Scopus ID
2-s2.0-85141527258 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder caused by maternal alloantibodies directed against paternally inherited human platelet alloantigens (HPAs) present on the surface of fetal and neonatal platelets. There are currently no approved therapies for the prevention of FNAIT. We report herein the ability of 2 human HPA-1a-specific therapeutic candidates, one a polyclonal, and the other a monoclonal antibody, to prevent alloimmunization in a novel preclinical mouse model of FNAIT. Both antibody preparations effected the rapid and complete elimination of HPA-1a+ platelets from circulation and prevented the development of HPA-1a alloantibodies. HPA-1a- female mice treated prophylactically with anti-HPA-1a antibody prior to exposure to HPA-1a+ platelets gave birth to HPA-1a+/- pups with significantly improved platelet counts and no bleeding symptoms. These preclinical data establish both the potential and threshold exposure targets for prophylactic treatment with HPA-1a-specific antibodies for the prevention of FNAIT in humans.
Author List
Zhi H, Sheridan D, Newman DK, Newman PJAuthors
Debra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinDebra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAntigens, Human Platelet
Female
Fetus
Humans
Integrin beta3
Isoantibodies
Mice
Pregnancy
Prenatal Care
Thrombocytopenia, Neonatal Alloimmune
