Pathogenesis and Control of Chronic Infections, INSERM, EFS, Université Montpellier 1, Montpellier, France.
Département d'Information Médicale, CHU de Montpellier, Montpellier, France.
J Transl Med. 2018 Oct 25;16(1):296. doi: 10.1186/s12967-018-1667-4.
Subclinical mastitis (SCM) is relatively common in lactating women and may be associated with HIV shedding in breast milk. The potential association between HIV infection and breast milk immunologic factors and immune response to SCM needs to be addressed.
In this cross-sectional study, SCM (Na/K ratio > 1) was tested in 165 mature breast milk samples collected from 40 HIV-infected women who didn't transmit HIV to their child by breastfeeding and 43 HIV-uninfected women enrolled in an interventional cohort in South-Africa (Vertical Transmission Study). The level of 33 immune markers related to Th1/Th2 related response, inflammation and bacterial exposure were compared in ART-naive HIV-infected versus HIV-uninfected women. The associations between HIV infection and SCM on the concentration of immune factors were tested separately by Wilcoxon rank-sum test and corrected for false discovery rate. To control for potential confounder effects and take into account the clustering of breast milk samples from a single woman, multivariate mixed linear models adjusted on child age at the time of sampling were performed for each immune factor.
Subclinical mastitis was detected in 15 (37.5%) HIV-infected women and 10 (23.3%) HIV-uninfected women. In the absence of SCM, the breast milk levels of IP-10 and MIG were higher and IL1-RA lower in HIV-infected women than in HIV-uninfected women (respectively p < 0.001, p = 0.001, p = 0.045). In HIV-uninfected women, SCM was characterized by a robust immune response with higher concentrations of a broad panel of Th1 and inflammatory related immune markers than in samples without SCM. By contrast, in HIV-infected women a limited number of immune markers were increased and lower increases were observed in samples with SCM than without SCM.
HIV infection in ART-naïve women was associated with elevated breast milk levels of IP-10 and MIG, which areTh1-related cytokines induced by IFN-γ. During SCM, a lower and narrower immune response was observed in HIV-infected than HIV-uninfected women, suggesting that HIV infection affects the capacity of the mammary gland to respond to SCM.
亚临床乳腺炎（SCM）在哺乳期妇女中较为常见，可能与母乳中 HIV 的脱落有关。HIV 感染与母乳免疫因素以及对 SCM 的免疫反应之间的潜在关联需要得到解决。
在这项横断面研究中，检测了来自南非一个干预队列（垂直传播研究）中 40 名未通过母乳喂养将 HIV 传染给孩子的 HIV 感染妇女和 43 名未感染 HIV 的妇女的 165 份成熟母乳样本中的 SCM（Na/K 比值>1）。比较了初治 HIV 感染与未感染妇女中与 Th1/Th2 相关反应、炎症和细菌暴露相关的 33 种免疫标志物的水平。通过 Wilcoxon 秩和检验分别测试了 HIV 感染与 SCM 对免疫因子浓度的关联，并对假发现率进行了校正。为了控制潜在的混杂因素效应，并考虑到来自单个妇女的母乳样本的聚类，对每个免疫因子进行了调整儿童在采样时年龄的多变量混合线性模型。
15 名（37.5%）HIV 感染妇女和 10 名（23.3%）未感染 HIV 的妇女中检测到亚临床乳腺炎。在没有 SCM 的情况下，与未感染 HIV 的妇女相比，感染 HIV 的妇女的 IP-10 和 MIG 水平更高，IL1-RA 水平更低（分别为 p<0.001、p=0.001、p=0.045）。在未感染 HIV 的妇女中，SCM 的特点是广泛的 Th1 和炎症相关免疫标志物的浓度升高，这表明存在强烈的免疫反应，与没有 SCM 的样本相比。相比之下，在感染 HIV 的妇女中，只有少数免疫标志物增加，并且在有 SCM 的样本中增加幅度较低。
在未接受抗逆转录病毒治疗的妇女中，HIV 感染与 IP-10 和 MIG 水平升高有关，IP-10 和 MIG 是由 IFN-γ诱导的 Th1 相关细胞因子。在 SCM 期间，与未感染 HIV 的妇女相比，感染 HIV 的妇女的免疫反应较低且较窄，这表明 HIV 感染影响了乳腺对 SCM 的反应能力。
