Human Epididymis Protein 4 and Secretory Leukocyte Protease Inhibitor in Vaginal Fluid Relation to Vaginal Components and Bacterial Composition
Human Epididymis Protein 4 and Secretory Leukocyte Protease Inhibitor in Vaginal Fluid Relation to Vaginal Components and Bacterial Composition
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DOI：
10.1177/1933719113503416
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发表时间：
2014-04-01
影响因子：
2.9
通讯作者：
Witkin, Steven S.
中科院分区：
文献类型：
--
作者：
Orfanelli, Theofano;Jayaram, Aswathi;Witkin, Steven S.
人附睾蛋白4（HE 4）是一种蛋白酶抑制剂，是最近发现的卵巢癌血清生物标志物。尚未评估健康女性生殖道中HE 4的特性。我们评估了HE 4和第二种阴道蛋白酶抑制剂分泌性白细胞蛋白酶抑制剂（SLPI）与阴道先天免疫介质或蛋白酶浓度以及阴道细菌群落类型之间的关联。从18名健康育龄妇女收集阴道分泌物，并通过酶联免疫吸附测定法测定HE 4、SLPI、激肽释放酶5、组织蛋白酶B、白细胞介素1 β（IL-1）、IL-1受体拮抗剂（IL-1 ra）、甘露糖结合凝集素（MBL）、可诱导的70 kDa热休克蛋白和基质金属蛋白酶（MMP）-8的浓度。16名妇女阴道细菌群落的物种组成的特点是来自16 S细菌核糖体RNA基因的测序扩增子。通过斯皮尔曼秩相关检验分析任何2种测定之间的相关性。通过Mann-Whitney U检验分析HE 4和SLPI浓度的差异以及可溶性组分和阴道群落类型之间的差异。阴道HE 4浓度与IL-1 β（P = 0.0152）、IL-1 ra（P = 0.0061）、MBL（P = 0.0100）和MMP-8（P = 0.0315）水平呈正相关，而SLPI水平与之无关。当阴道加德纳菌占主导地位时，阴道HE 4水平中位数以及MBL、IL-1 β、IL-1 ra和MMP-8的浓度最高。HE 4、蛋白酶水平升高、免疫介质和高比例G迷走细胞之间的关联强烈表明HE 4是女性生殖道中促炎免疫应答的组分。
Human epididymis protein 4 (HE4) is a protease inhibitor and a recently identified serum biomarker for ovarian cancer. Properties of HE4 in the genital tract of healthy women have not been evaluated. We evaluated associations between HE4 and a second vaginal protease inhibitor, secretory leukocyte protease inhibitor (SLPI), with vaginal concentrations of innate immune mediators or proteases and with the types of vaginal bacterial communities. Vaginal secretions were collected from 18 healthy reproductive age women and assayed by enzyme-linked immunosorbent assay for concentrations of HE4, SLPI, kallikrein 5, cathepsin B, interleukin 1 beta (IL-1), IL-1 receptor antagonist (IL-1 ra), mannose-binding lectin (MBL), the inducible 70-kDa heat shock protein, and matrix metalloproteinase (MMP)-8. The species composition of vaginal bacterial communities in 16 women was characterized by sequencing amplicons derived from 16S bacterial ribosomal RNA genes. Correlations between any 2 assays were analyzed by the Spearman rank correlation tests. Differences in the concentrations of HE4 and SLPI, and between soluble components and vaginal community types, were analyzed by the Mann-Whitney U tests. Vaginal HE4 concentrations, but not SLPI levels, were positively correlated with levels of IL-1 beta (P = .0152), IL-1ra (P = .0061), MBL (P = .0100), and MMP-8 (P = .0315). The median vaginal HE4 level, as well as concentrations of MBL, IL-1 beta, IL-1ra, and MMP-8, was highest when Gardnerella vaginalis dominated a vaginal community. The association between HE4, elevated levels of proteases, immune mediators and high proportions of G vaginalis strongly suggests that HE4 is a component of the proinflammatory immune response in the female genital tract.