HIV感染女性阴道宫颈洗液中细胞因子检测及其与高危型人乳头瘤病毒的关联性

Detection of cytokines in cervicovaginal lavage in HIV-infected women and its association with high-risk human papillomavirus

Frontiers in Immunology

影响因子:5.9

分区:医学2区 / 免疫学2区

发表日期:2024

作者: Sandra Schindler, Eduardo Netto, Felice Deminco, Camila A Figueiredo, Candace Machado de Andrade, Amanda Rosa Alves, Carlos Brites

DOI: 10.3389/fimmu.2024.1416204

摘要

HIV/AIDS感染女性（WLHA）中高危型HPV（HR-HPV）感染和宫颈上皮内瘤变（CIN）的发生率增加，尽管采用了新一代抗逆转录病毒药物，但其发生宫颈癌的风险依然较高。本研究旨在评估WLHA局部免疫反应中不同细胞因子的浓度，这对于理解该人群中HPV相关癌症的发病机制至关重要。在巴西萨尔瓦多Edgard Santos大学医院，2019年12月至2023年4月期间，采用Luminex®技术分析106名WLHA宫颈阴道洗液（CVL）中IL-1β、IL-2、IL-4、IL-6、IL-10、IFN-γ、TNF-α、IP-10、GM-CSF和MIP-1α等细胞因子的水平。所有受试者还检测了沙眼衣原体和淋病奈瑟菌感染，并接受阴道镜检查、巴氏涂片及Nugent评分。所有WLHA均进行了HIV血浆病毒载量（VL）和CD4细胞计数检测。本研究中，22.6%的WLHA感染了HR-HPV（24/106）。感染HR-HPV的患者中，66.7%检测到IL-10水平高于阴性者的40.2%（p=0.02）。绝经前妇女中，IL-6（51.4%）或IP-10（58.3%）的检测率高于绝经妇女（IL-6为26.5%，IP-10为32.4%，p=0.013和p=0.011）。阴道炎与IP-10（24.2% vs. 61.4%）和IFN-γ（39.4% vs. 68.6%）的检测呈负相关（p<0.001和p=0.005）。IL-1β（66.7% vs. 37.1%）和IL-10（63.6% vs. 37.1%）的阳性相关性显著（p=0.005和p=0.01）。病毒载量和CD4水平未与所研究的细胞因子相关联。我们发现IL-10与CVL中HPV感染呈正相关，提示在HIV/HPV合并感染患者中，Th2反应占优势。然而，还需要更长随访的研究以评估IL-10与HPV感染、CIN及宫颈癌之间的关系。

Abstract

Women living with HIV/AIDS (WLHA) have an increased prevalence of high-risk HPV infection (HR-HPV) and cervical intraepithelial neoplasia (CIN) and a greater risk of cervical cancer despite access to a new generation of antiretroviral therapy. The aim of this study is to evaluate the concentrations of different cytokines involved in the local immune response in WLHA, which is fundamental for understanding the pathogenesis of HPV-related cancer in this population.IL-1β, IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, IP-10, GM-CSF, and MIP-1α were investigated in the cervicovaginal lavage (CVL) of 106 WLHA attending at Hospital Universitario Professor Edgard Santos in Salvador, Bahia, Brazil, during the period December 2019 to April 2023 by Luminex®. All participants were also tested for Chlamydia trachomatis and Neisseria gonorrhoeae and underwent colposcopy, Pap smear, and Nugent score. HIV plasma viral load (VL) and CD4 cell count were performed for all WLHA.In this study, 22.6% (24/106) of WLHA were infected with HR-HPV. A higher proportion of patients with HR-HPV (66.7%) had detectable levels of IL-10 than those negative ones (40.2%, p = 0.02). More premenopausal women had either IL-6 (51.4%) or IP-10 (58.3%) than those in menopausal status (26.5% for IL-6 and 32.4% for IP-10, p = 0.013 and p = 0.011, respectively). Vaginosis was negatively associated with detection of IP-10 (24.2% vs. 61.4%, p < 0.001) and INF-γ (39.4% vs. 68.6%, p = 0.005). A positive association was detected for IL-1β (66.7 vs. 37.1%, p = 0.005) and IL-10 (63.6% vs. 37.1%, p = 0.01). VL and CD4 were not associated with the studied cytokines.We demonstrated a positive association between IL-10 and HPV infection in CVL, suggesting the predominance of the Th2 response in HIV/HPV co-infected patients. However, further studies with longer follow-up will be needed to evaluate the association of IL-10 with HPV infection, CIN, and cervical cancer in WLHA.