Immune Activation in the Female Genital Tract: Expression Profiles of Soluble Proteins in Women at High Risk for HIV Infection.
Immune Activation in the Female Genital Tract: Expression Profiles of Soluble Proteins in Women at High Risk for HIV Infection.
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DOI：
10.1371/journal.pone.0143109
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Shattock RJ
中科院分区：
文献类型：
--
作者：
Francis SC;Hou Y;Baisley K;van de Wijgert J;Watson-Jones D;Ao TT;Herrera C;Maganja K;Andreasen A;Kapiga S;Coulton GR;Hayes RJ;Shattock RJ
为了可靠地评估包括疫苗和杀菌剂在内的新的生物医学预防策略的安全性，需要可溶的宫颈阴道炎症、免疫激活和艾滋病毒感染风险生物标志物。然而，更全面地了解HIV感染高风险妇女的表达谱对于在3期试验环境中有效使用这些潜在的生物标志物至关重要。我们在100名HIV阴性的HIV感染高危妇女的宫颈阴道灌洗液样本中检测了45种可溶性蛋白和多肽。研究人员对妇女进行了一个月经周期的随访，以调查激素避孕、月经周期、近期性接触和阴道内实践对她们的调节作用。注射DMPA的女性先天和适应性免疫系统中几种可溶性蛋白的浓度增加，包括IL-1α、IL-1β、IL-2、MIP-1β、IP-10、IL-8、TGF-β、HBD4、IgA、IgG1和IgG2。使用联合口服避孕药的女性也有类似的特征。与排卵前相比，排卵后样品中的浓度存在差异，特别是免疫球蛋白的增加。前列腺特异性抗原升高，表明近期性暴露，与IL-6、MCP-1和SLPI升高以及GM-CSF和HBD3降低相关。所确定的特征特征可能对评估不同生物医学干预策略的潜在安全性和对艾滋病毒感染风险的影响至关重要。
Soluble cervicovaginal biomarkers of inflammation, immune activation and risk of HIV acquisition are needed to reliably assess the safety of new biomedical prevention strategies including vaccines and microbicides. However, a fuller understanding of expression profiles in women at high risk for HIV infection is crucial to the effective use of these potential biomarkers in Phase 3 trial settings. We have measured 45 soluble proteins and peptides in cervicovaginal lavage samples from 100 HIV negative women at high risk for HIV infection. Women were followed over one menstrual cycle to investigate modulation by hormonal contraception, menstrual cycle phase, recent sexual exposure and intravaginal practices. Women using injectable DMPA had increased concentration of several soluble proteins of the innate and adaptive immune system, including IL-1α, IL-1β, IL-2, MIP-1β, IP-10, IL-8, TGF-β, HBD4, IgA, IgG1, and IgG2. Women using combined oral contraceptives had a similar signature. There were differences in concentrations among samples from post-ovulation compared to pre-ovulation, notably increased immunoglobulins. Increased prostate-specific antigen, indicative of recent sexual exposure, was correlated with increased IL-6, MCP-1, and SLPI, and decreased GM-CSF and HBD3. The identified signature profiles may prove critical in evaluating the potential safety and impact on risk of HIV acquisition of different biomedical intervention strategies.