Plasma concentration of injectable contraceptive correlates with reduced cervicovaginal growth factor expression in South African women.,Mucosal Immunology

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Plasma concentration of injectable contraceptive correlates with reduced cervicovaginal growth factor expression in South African women.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2020-01-02 , DOI: 10.1038/s41385-019-0249-y
Refilwe P Molatlhegi _{1,

2} , Lenine J Liebenberg _{1,

2} , Alasdair Leslie ₃ , Laura Noel-Romas _{4,

5} , Amanda Mabhula ₃ , Nobuhle Mchunu ₁ , Michelle Perner _{4,

5} , Kenzie Birse _{4,

5} , Sinaye Ngcapu _{1,

2} , John H Adamson ₃ , Katya Govender ₃ , Nigel J Garrett ₁ , Natasha Samsunder ₁ , Adam D Burgener _{4,

5,

6,

7} , Salim S Abdool Karim _{1,

8} , Quarraisha Abdool Karim _{1,

8} , Jo-Ann S Passmore _{1,

9} , Lyle R McKinnon _{1,

4,

5}

Affiliation

Long-acting injectable contraceptives have been associated with mucosal immune changes and increased HIV acquisition, but studies have often been hampered by the inaccuracy of self-reported data, unknown timing of injection, and interactions with mucosal transmission co-factors. We used mass spectrometry to quantify the plasma concentrations of injectable contraceptives in women from the CAPRISA004 study (n = 664), with parallel quantification of 48 cytokines and >500 host proteins in cervicovaginal lavage. Higher DMPA levels were associated with reduced CVL concentrations of GCSF, MCSF, IL-16, CTACK, LIF, IL-1α, and SCGF-β in adjusted linear mixed models. Dose-dependent relationships between DMPA concentration and genital cytokines were frequently observed. Unsupervised clustering of host proteins by DMPA concentration suggest that women with low DMPA had increases in proteins associated with mucosal fluid function, growth factors, and keratinization. Although DMPA was not broadly pro-inflammatory, DMPA was associated with increased IP-10 in HSV-2 seropositive and older women. DMPA-cytokine associations frequently differed by vaginal microbiome; in non-Lactobacillus-dominant women, DMPA was associated with elevated IL-8, MCP-1, and IP-10 concentrations. These data confirm a direct, concentration-dependant effect of DMPA on functionally important immune factors within the vaginal compartment. The biological effects of DMPA may vary depending on age, HSV-2 status, and vaginal microbiome composition.

中文翻译：

注射避孕药的血浆浓度与南非妇女宫颈阴道生长因子表达降低有关。

长效注射避孕药与粘膜免疫变化和 HIV 感染增加有关，但研究经常受到自我报告数据不准确、注射时间未知以及与粘膜传播辅助因子相互作用的阻碍。我们使用质谱法对来自 CAPRISA004 研究 (n = 664) 的女性注射避孕药的血浆浓度进行了量化，同时对宫颈阴道灌洗液中的 48 种细胞因子和 >500 种宿主蛋白进行了平行量化。在调整后的线性混合模型中，较高的 DMPA 水平与 GCSF、MCSF、IL-16、CTACK、LIF、IL-1α 和 SCGF-β 的 CVL 浓度降低相关。经常观察到 DMPA 浓度与生殖细胞因子之间的剂量依赖关系。通过 DMPA 浓度对宿主蛋白质进行无监督聚类表明，DMPA 低的女性与粘膜液功能、生长因子和角化相关的蛋白质增加。尽管 DMPA 不是广泛的促炎剂，但 DMPA 与 HSV-2 血清反应阳性和老年妇女的 IP-10 增加有关。DMPA-细胞因子关联通常因阴道微生物组而异；在非乳酸菌占优势的女性中，DMPA 与 IL-8、MCP-1 和 IP-10 浓度升高有关。这些数据证实了 DMPA 对阴道隔室内功能重要的免疫因子的直接、浓度依赖性影响。DMPA 的生物学效应可能因年龄、HSV-2 状态和阴道微生物组成而异。和角质化。尽管 DMPA 不是广泛的促炎剂，但 DMPA 与 HSV-2 血清反应阳性和老年妇女的 IP-10 增加有关。DMPA-细胞因子关联通常因阴道微生物组而异；在非乳酸菌占优势的女性中，DMPA 与 IL-8、MCP-1 和 IP-10 浓度升高有关。这些数据证实了 DMPA 对阴道隔室内功能重要的免疫因子的直接、浓度依赖性影响。DMPA 的生物学效应可能因年龄、HSV-2 状态和阴道微生物组成而异。和角质化。尽管 DMPA 不是广泛的促炎剂，但 DMPA 与 HSV-2 血清反应阳性和老年妇女的 IP-10 增加有关。DMPA-细胞因子关联通常因阴道微生物组而异；在非乳酸菌占优势的女性中，DMPA 与 IL-8、MCP-1 和 IP-10 浓度升高有关。这些数据证实了 DMPA 对阴道隔室内功能重要的免疫因子的直接、浓度依赖性影响。DMPA 的生物学效应可能因年龄、HSV-2 状态和阴道微生物组成而异。MCP-1 和 IP-10 浓度。这些数据证实了 DMPA 对阴道隔室内功能重要的免疫因子的直接、浓度依赖性影响。DMPA 的生物学效应可能因年龄、HSV-2 状态和阴道微生物组成而异。MCP-1 和 IP-10 浓度。这些数据证实了 DMPA 对阴道隔室内功能重要的免疫因子的直接、浓度依赖性影响。DMPA 的生物学效应可能因年龄、HSV-2 状态和阴道微生物组成而异。

更新日期：2020-01-02

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