Successful prenatal therapy for anti-CD36-mediated severe FNAIT by deglycosylated antibodies in a novel murine model

胎儿 抗体 胎盘 单克隆抗体 CD36 医学 多克隆抗体 新生儿同种免疫性血小板减少症 免疫学 怀孕 男科 单克隆 生物 内科学 受体 遗传学
作者
Xiuzhang Xu,Dawei Chen,Xin Ye,Wenjie Xia,Yaori Xu,Yangkai Chen,Yuan Shao,Jing Deng,Haoqiang Ding,Jing Liu,Jiali Wang,Heyu Ni,Yongshui Fu,Sentot Santoso
出处
期刊:Blood [Elsevier BV]
卷期号:138 (18): 1757-1767 被引量:10
标识
DOI:10.1182/blood.2021011131
摘要

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.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
刘佳佳完成签到 ,获得积分10
1秒前
1秒前
monoklatt发布了新的文献求助10
1秒前
Kevin发布了新的文献求助10
1秒前
Orange应助樱悼柳雪采纳,获得10
2秒前
2秒前
ZYT723完成签到,获得积分10
2秒前
SH发布了新的文献求助10
3秒前
3秒前
顾矜应助彩色蘑菇采纳,获得10
3秒前
sisyphus_yy完成签到 ,获得积分10
4秒前
轻松的惜芹应助Djtc采纳,获得20
4秒前
5秒前
Donby发布了新的文献求助10
5秒前
于浩完成签到 ,获得积分10
5秒前
QZZ发布了新的文献求助10
5秒前
6秒前
mzf发布了新的文献求助10
6秒前
zz完成签到,获得积分10
7秒前
7秒前
SciGPT应助wjx采纳,获得10
7秒前
7秒前
SHD发布了新的文献求助10
7秒前
清爽玉米完成签到,获得积分10
8秒前
vialavilda发布了新的文献求助10
8秒前
8秒前
英俊的铭应助zzrg采纳,获得10
8秒前
8秒前
复杂的兔子完成签到,获得积分10
9秒前
keke完成签到,获得积分10
9秒前
十一发布了新的文献求助10
9秒前
阿俊发布了新的文献求助10
10秒前
10秒前
MoriZhang完成签到,获得积分10
10秒前
10秒前
知了完成签到,获得积分10
10秒前
Ava应助小赐采纳,获得10
10秒前
FZD是小福星完成签到,获得积分10
11秒前
11秒前
高分求助中
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
Effective Learning and Mental Wellbeing 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3974856
求助须知:如何正确求助?哪些是违规求助? 3519400
关于积分的说明 11198085
捐赠科研通 3255563
什么是DOI,文献DOI怎么找? 1797860
邀请新用户注册赠送积分活动 877208
科研通“疑难数据库(出版商)”最低求助积分说明 806219