In:
Blood, American Society of Hematology, Vol. 138, No. 18 ( 2021-11-04), p. 1757-1767
Abstract:
Recent studies have shown that maternal anti-CD36 antibodies represent a frequent cause of fetal/neonatal alloimmune thrombocytopenia (FNAIT) in Asian and African populations. However, little is known about the pathomechanism and antenatal treatment of anti-CD36–mediated FNAIT. Here, we established a novel animal model to examine the clinical features of pups from immunized Cd36−/− female mice after breeding with wild-type male mice. Mild thrombocytopenia was observed, but high pup mortality was also documented (40.26%). Administration of intravenous immunoglobulin (IVIG) (1 g/kg) on days 7, 12, and 17 to immunized Cd36−/− mothers after breeding reduced fetal death (12.70%). However, delaying the IVIG administration series on days 10, 15, and 20 did not reduce fetal death (40.00%). In contrast, injection of deglycosylated anti-CD36 (deg-anti-CD36) polyclonal antibodies (5 mg/kg) on days 10, 15, and 20 significantly reduced fetal death (5.26%). Subsequently, monoclonal antibodies (mAbs) against mouse CD36 were developed, and one clone producing high-affinity anti-CD36 (termed 32-106) effectively inhibited maternal antibody binding and was therefore selected. Using the same approach of deg-anti-CD36, the administration of deg-32-106 significantly reduced fetal death (2.17%). Furthermore, immunized Cd36−/− mothers exhibited placental deficiency. Accordingly, maternal anti-CD36 antibodies inhibited angiogenesis of placenta endothelial cells, which could be restored by deg-32-106. In summary, maternal anti-CD36 antibodies caused a high frequency of fetal death in our animal model, associated with placental dysfunction. This deleterious effect could be diminished by the antenatal administration of IVIG and deg-mAb 32-106. Interestingly, treatment with deg-32-106 seems more beneficial considering the lower dose, later start of treatment, and therapy success.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.2021011131
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2021
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
