检测HIV感染妇女宫颈阴道灌洗中的细胞因子及其与高风险人乳头瘤病毒的关联

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:5.90000

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

摘要

患有艾滋病毒/艾滋病（WLHA）的妇女的高危HPV感染（HR-HPV）和宫颈上皮内肿瘤（CIN）的患病率增加，尽管接受了新一代的抗逆转录病毒治疗，但患有宫颈癌的风险更大。 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）在2019年12月至2023年4月的Luminex®期间，在巴西巴伊亚萨尔瓦多的医院大学教授Edgard Santos参加了106个WLHA。还测试了所有参与者的沙眼衣原体和淋病奈瑟氏菌的测试，并进行了阴道镜检查，子宫颈抹片检查和Nugent评分。所有WLHA进行了HIV血浆病毒载量（VL）和CD4细胞计数。在这项研究中，用HR-HPV感染了22.6％（24/106）的WLHA。与阴性患者相比，HR-HPV患者比例更高（66.7％）的IL-10水平（40.2％，p = 0.02）。绝经前妇女的具有IL-6（51.4％）或IP-10（58.3％）的绝经状态（IL-6的26.5％，IP-10的26.5％，P = 0.013和P = 0.011）。阴道病与检测IP-10（24.2％对61.4％，P <0.001）和INF-γ（39.4％vs. 68.6％，P = 0.005）负相关。检测到IL-1β的阳性关联（66.7 vs. 37.1％，p = 0.005）和IL-10（63.6％vs. 37.1％，p = 0.01）。 VL和CD4与所研究的细胞因子无关。我们在CVL中表现出IL-10和HPV感染之间的阳性关联，这表明HIV/HPV共感染的患者中Th2反应的占主导地位。但是，将需要进行更长的随访的进一步研究，以评估WLHA中IL-10与HPV感染，CIN和宫颈癌的关联。

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.