Ono E, Nunes dos Santos A M, de Menezes Succi R C, Machado D M, de Angelis D S A, Salomão R, Kallás E G, de Moraes-Pinto M I
Disciplina de Infectologia Pediátrica, Universidade Federal de São Paulo.
Braz J Med Biol Res. 2008 Aug;41(8):700-8. doi: 10.1590/s0100-879x2008000800011.
The immune consequences of in utero HIV exposure to uninfected children whose mothers were submitted to highly active antiretroviral therapy (HAART) during gestation are not well defined. We evaluated 45 HIV-exposed uninfected (ENI) neonates and 45 healthy unexposed control (CT) neonates. All HIV-infected mothers received HAART during pregnancy, and the viral load at delivery was <50 copies/mL for 56.8%. Twenty-three ENI neonates were further evaluated after 12 months and compared to 23 unexposed healthy age-matched infants. Immunophenotyping was performed by flow cytometry in cord and peripheral blood. Cord blood lymphocyte numbers did not differ between groups. However, ENI neonates had a lower percentage of naive T cells than CT neonates (CD4+, 76.6 vs 83.1%, P < 0.001; CD8+, 70.9 vs 79.6%, P = 0.003) and higher percentages of central memory T cells than CT neonates (CD4+, 13.9 vs 8.7%, P < 0.001; CD8+, 8.6 vs 4.8%, P = 0.001). CD38 mean fluorescence intensity of T cells was higher in ENI neonates (CD4+, 62.2 vs 52.1, P = 0.007; CD8+, 47.7 vs 35.3, P < 0.001). At 12 months, ENI infants still had higher mean fluorescence intensity of CD38 on T cells (CD4+, 34.2 vs 23.3, P < 0.001; CD8+, 26.8 vs 19.4, P = 0.035). Despite effective maternal virologic control at delivery, HIV-exposed uninfected children were born with lower levels of naive T cells. Immune activation was present at birth and remained until at least 12 months of age, suggesting that in utero exposure to HIV causes subtle immune abnormalities.
母亲在妊娠期接受高效抗逆转录病毒疗法（HAART）的情况下，子宫内暴露于HIV的未感染儿童的免疫后果尚未明确界定。我们评估了45名暴露于HIV的未感染（ENI）新生儿和45名健康的未暴露对照（CT）新生儿。所有感染HIV的母亲在孕期均接受了HAART，分娩时病毒载量<50拷贝/mL的占56.8%。23名ENI新生儿在12个月后进一步接受评估，并与23名年龄匹配的未暴露健康婴儿进行比较。通过流式细胞术对脐带血和外周血进行免疫表型分析。两组之间脐带血淋巴细胞数量无差异。然而，ENI新生儿的初始T细胞百分比低于CT新生儿（CD4+，76.6%对83.1%，P<0.001；CD8+，70.9%对79.6%，P = 0.003），而中枢记忆T细胞百分比高于CT新生儿（CD4+，13.9%对8.7%，P<0.001；CD8+，8.6%对4.8%，P = 0.001）。ENI新生儿T细胞的CD38平均荧光强度更高（CD4+，62.2对52.1，P = 0.007；CD8+，47.7对35.3，P<0.001）。在12个月时，ENI婴儿T细胞上CD38的平均荧光强度仍然较高（CD4+，34.2对23.3，P<0.001；CD8+，26.8对19.4，P = 0.035）。尽管分娩时母亲病毒学控制有效，但暴露于HIV的未感染儿童出生时初始T细胞水平较低。免疫激活在出生时即存在，并至少持续至12月龄，这表明子宫内暴露于HIV会导致细微的免疫异常。
