High Antibodies to VAR2CSA in Response to Malaria Infection Are Associated With Improved Birthweight in a Longitudinal Study of Pregnant Women.
High Antibodies to VAR2CSA in Response to Malaria Infection Are Associated With Improved Birthweight in a Longitudinal Study of Pregnant Women.
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DOI：
10.3389/fimmu.2021.644563
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发表时间：
2021
影响因子：
7.3
通讯作者：
Fowkes FJI
中科院分区：
文献类型：
--
作者：
McLean ARD;Opi DH;Stanisic DI;Cutts JC;Feng G;Ura A;Mueller I;Rogerson SJ;Beeson JG;Fowkes FJI
孕妇感染恶性疟原虫的风险增加，这与低出生体重和早产有关。VAR 2CSA是一种在被寄生的红细胞表面上表达的变体表面抗原，能够在胎盘中隔离。很少有研究前瞻性地研究怀孕期间的抗体反应与随后的不良出生结果之间的关系，非洲以外的数据有限。在301名妇女中测量了针对VAR 2CSA结构域（DBL 3; DBL 5）和表达VAR 2CSA的胎盘结合恶性疟原虫分离株（PfCS 2-IE）的IgG水平，这些妇女在怀孕中期首次接受产前护理时登记（中位数= 26周，下四分位数和上四分位数= 22，28）。通过调整混杂因素的线性回归和逻辑回归评估入组时抗体水平与胎盘感染、出生体重和分娩时估计胎龄之间的关系。对于所有结局，评估了受试者入组时妊娠和外周血恶性疟原虫感染的影响。在入组时感染恶性疟原虫的妇女中，VAR 2CSA抗体水平较高的妇女，（第75百分位数）的婴儿平均出生体重较高（根据抗体反应，估计值从+35 g到+149 g不等），并降低了胎盘感染的调整几率（aOR估计值从0.17到0.80不等），相对于VAR 2CSA抗体水平较低（第25百分位数）的女性。然而，在入组时未感染的女性中，较高的VAR 2CSA抗体与胎盘感染的几率增加相关（aOR估计值从1.10到2.24不等）。当怀孕中期感染时，对表达VAR 2CSA的寄生虫的更好的免疫应答可能有助于防止不良妊娠结局。
Pregnant women have an increased risk of P. falciparum infection, which is associated with low birth weight and preterm delivery. VAR2CSA, a variant surface antigen expressed on the parasitized erythrocyte surface, enables sequestration in the placenta. Few studies have prospectively examined relationships between antibody responses during pregnancy and subsequent adverse birth outcomes, and there are limited data outside Africa. Levels of IgG against VAR2CSA domains (DBL3; DBL5) and a VAR2CSA-expressing placental-binding P. falciparum isolate (PfCS2-IE) were measured in 301 women enrolled at their first visit to antenatal care which occurred mid-pregnancy (median = 26 weeks, lower and upper quartiles = 22, 28). Associations between antibody levels at enrolment and placental infection, birthweight and estimated gestational age at delivery were assessed by linear and logistic regression with adjustment for confounders. For all outcomes, effect modification by gravidity and peripheral blood P. falciparum infection at enrolment was assessed. Among women who had acquired P. falciparum infection at enrolment, those with higher levels of VAR2CSA antibodies (75th percentile) had infants with higher mean birthweight (estimates varied from +35g to +149g depending on antibody response) and reduced adjusted odds of placental infection (aOR estimates varied from 0.17 to 0.80), relative to women with lower levels (25th percentile) of VAR2CSA antibodies. However, among women who had not acquired an infection at enrolment, higher VAR2CSA antibodies were associated with increased odds of placental infection (aOR estimates varied from 1.10 to 2.24). When infected by mid-pregnancy, a better immune response to VAR2CSA-expressing parasites may contribute to protecting against adverse pregnancy outcomes.
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作者：
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