Concomitant Imbalances of Systemic and Mucosal Immunity Increase HIV Acquisition Risk.
Concomitant Imbalances of Systemic and Mucosal Immunity Increase HIV Acquisition Risk.
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DOI：
10.1097/qai.0000000000002299
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发表时间：
2020-05-01
期刊：
影响因子：
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通讯作者：
Fichorova RN
中科院分区：
文献类型：
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作者：
Morrison CS;Chen PL;Yamamoto H;Gao X;Chipato T;Anderson S;Barbieri R;Salata R;Doncel GF;Fichorova RN
我们之前报道过，宫颈 RANTES 增加和分泌性白细胞蛋白酶抑制剂 (SLPI) 减少与育龄妇女感染 HIV 的风险较高之间存在关联。我们现在研究伴随改变的全身免疫和宫颈免疫对这种风险的相互作用。我们每季度访问 218 名 HIV 血清转化者和 784 名血清阴性女性，测量了 4390 份宫颈标本和 2390 份配对血清标本中的免疫生物标志物。我们评估了促炎（IL-1β、IL-6、IL-8、MIP-3α 和 RANTES）、抗炎（IL-1RA 和 SLPI）、血管活化（血管内皮生长因子和细胞间粘附分子-1）和防御素 (BD2) 宫颈生物标志物以及全身（外周血）C 反应蛋白 (CRP)、IL-6、IL-7 和 sCD14 作为免疫指标。失调。生物标志物水平经过 Box-Cox 转换，并根据所有 HIV 阴性就诊的前四分位或高于/低于中位水平计算 HIV 获得的比值比。随后的 HIV 感染与 14 个个体生物标志物中的 5 个相关：低全身 CRP [比值比 (OR) = 1.49, 1.21–1.83] 和 IL-6 (OR = 1.23, 1.00–1.51)、高颈椎 BD-2 (OR = 1.33, 1.11–1.58) 和 RANTES (OR = 1.20, 1.01–1.43）和低宫颈IL-1RA（OR = 0.65，0.48–0.86）。低全身 CRP 伴随宫颈免疫力改变，尤其是高 BD2，带来最高的 HIV 风险 (1.63, 1.29–2.05)。当全身性 CRP 低同时出现时，会出现其他风险增加的标志物： 全身性 IL-6 和 IL-7 低（OR= 1.53、1.18–1.97）；高宫颈IL-8和MIP-3α（OR = 1.40，1.07–1.83）；高宫颈IL-1β和IL-6（OR = 1.43，1.09–1.86）；或低颈椎 SLPI（OR = 1.36，1.08–1.71）。外周和粘膜免疫的变化可能先于女性感染艾滋病毒，并使其易于感染艾滋病毒。单独抑制全身免疫（即低CRP）或与不平衡的宫颈先天免疫（高促炎介质和低抗炎介质）相结合表明更容易受到感染。了解这些对艾滋病毒易感性的综合影响对于预防新的感染至关重要。
We previously reported association of increased cervical RANTES and decreased secretory leukocyte protease inhibitor (SLPI) with higher risk of HIV acquisition in reproductive-age women. We now examine the interaction of concomitantly altered systemic and cervical immunity on such risk. We measured immune biomarkers in 4390 cervical and 2390 paired serum specimens at quarterly visits in 218 HIV seroconverters and 784 seronegative women. We assessed proinflammatory (IL-1β, IL-6, IL-8, MIP-3α, and RANTES), anti-inflammatory (IL-1RA and SLPI), vascular activation (vascular endothelial growth factor and Intercellular Adhesion Molecule-1) and defensin (BD2) cervical biomarkers and systemic (peripheral blood) C reactive protein (CRP), IL-6, IL-7, and sCD14 as indicators of immune dysregulation. Biomarker levels were Box–Cox transformed and odds ratios for HIV acquisition calculated based on top quartile or higher/lower than median levels for all HIV-negative visits. Subsequent HIV acquisition was associated with 5 of 14 individual biomarkers: low systemic CRP [odds ratio (OR) = 1.49, 1.21–1.83] and IL-6 (OR = 1.23, 1.00–1.51), high cervical BD-2 (OR = 1.33, 1.11–1.58) and RANTES (OR = 1.20, 1.01–1.43), and low cervical IL-1RA (OR = 0.65, 0.48–0.86). Low systemic CRP concomitant with altered cervical immunity, especially high BD2, conveyed highest HIV risk (1.63, 1.29–2.05). Additional markers of increased risk emerged when low systemic CRP coincided with: low systemic IL-6 and IL-7 (OR= 1.53, 1.18–1.97); high cervical IL-8 and MIP-3α (OR = 1.40, 1.07–1.83); high cervical IL-1β and IL-6 (OR = 1.43, 1.09–1.86); or low cervical SLPI (OR = 1.36, 1.08–1.71). Changes in both peripheral and mucosal immunity may precede and predispose women to HIV infection. Suppressed systemic immunity (ie, low CRP) alone or in combination with imbalanced cervical innate immunity (high proinflammatory and low anti-inflammatory mediators) indicated increased vulnerability to infection. Understanding these combined effects on HIV susceptibility is essential to preventing new infections.