Bosire Rose, John-Stewart Grace C, Mabuka Jennifer M, Wariua Grace, Gichuhi Christine, Wamalwa Dalton, Ruzinski John, Goodman Richard, Lohman Barbara, Mbori-Ngacha Dorothy A, Overbaugh Julie, Farquhar Carey
Department of Pediatrics, University of Nairobi, Nairobi, Kenya.
AIDS Res Hum Retroviruses. 2007 Feb;23(2):198-203. doi: 10.1089/aid.2006.0125.
Alpha-defensins are proteins exhibiting in vitro anti-HIV-1 activity that may protect against mother-to-child transmission of HIV-1 via breast milk. Correlates of alpha-defensins in breast milk and transmission risk were determined in a cohort of HIV-1-infected pregnant women in Nairobi followed for 12 months postpartum with their infants. Maternal blood was collected antenatally and at delivery for HIV-1 viral load and infant HIV-1 infection status was determined < 48 h after birth and at months 1, 3, 6, 9, and 12. Breast milk specimens collected at month 1 were assayed for alpha-defensins, HIV-1 RNA, subclinical mastitis, and CC and CXC chemokines. We detected alpha-defensins in breast milk specimens from 108 (42%) of 260 HIV-1-infected women. Women with detectable alpha-defensins (> or =50 pg/ml) had a median concentration of 320 pg/ml and significantly higher mean breast milk HIV-1 RNA levels than women with undetectable alpha-defensins (2.9 log(10) copies/ml versus 2.5 log(10) copies/ml, p = 0.003). Increased alpha-defensins concentrations in breast milk were also associated with subclinical mastitis (Na (+)/K(+) ratio > 1) and increased breast milk chemokine levels. Overall, 40 (15%) infants were HIV-1 uninfected at birth and subsequently acquired HIV-1. There was no significant association between month 1 alpha-defensins and risk of HIV-1 transmission. In conclusion, alpha-defensins were associated with breast milk HIV-1 viral load, chemokine levels, and subclinical mastitis, all of which may alter risk of infant HIV-1 acquisition. Despite these associations there was no significant relationship between breast milk alpha-defensins and mother-to-child transmission, suggesting a complex interplay between breast milk HIV-1, inflammation, and antiinfective factors.
α-防御素是一类在体外具有抗HIV-1活性的蛋白质，可能通过母乳预防HIV-1的母婴传播。在内罗毕的一组感染HIV-1的孕妇及其婴儿产后随访12个月的队列中，确定了母乳中α-防御素与传播风险之间的关联。在产前和分娩时采集母体血液检测HIV-1病毒载量，在出生后<48小时以及第1、3、6、9和12个月时确定婴儿的HIV-1感染状况。在第1个月采集的母乳标本检测α-防御素、HIV-1 RNA、亚临床乳腺炎以及CC和CXC趋化因子。我们在260名感染HIV-1的女性中的108名（42%）的母乳标本中检测到了α-防御素。可检测到α-防御素（≥50 pg/ml）的女性，其α-防御素的中位浓度为320 pg/ml，且母乳中HIV-1 RNA的平均水平显著高于未检测到α-防御素的女性（2.9 log₁₀拷贝/ml对2.5 log₁₀拷贝/ml，p = 0.003）。母乳中α-防御素浓度升高还与亚临床乳腺炎（钠/钾比值>1）以及母乳趋化因子水平升高有关。总体而言，40名（15%）婴儿出生时未感染HIV-1，随后感染了HIV-1。第1个月时的α-防御素与HIV-1传播风险之间无显著关联。总之，α-防御素与母乳中HIV-1病毒载量、趋化因子水平以及亚临床乳腺炎有关，所有这些都可能改变婴儿感染HIV-1的风险。尽管存在这些关联，但母乳中的α-防御素与母婴传播之间无显著关系，这表明母乳中的HIV-1、炎症和抗感染因子之间存在复杂的相互作用。
