Picat Marie-Quitterie, Pellegrin Isabelle, Bitard Juliette, Wittkop Linda, Proust-Lima Cécile, Liquet Benoît, Moreau Jean-François, Bonnet Fabrice, Blanco Patrick, Thiébaut Rodolphe
Centre INSERM U1219 Bordeaux Population Health, Bordeaux, France.
Univ. Bordeaux, ISPED, Bordeaux, France.
PLoS One. 2017 Jan 3;12(1):e0169164. doi: 10.1371/journal.pone.0169164. eCollection 2017.
To unravel the complex relationships between cytomegalovirus-induced-, autoimmune-induced responses, microbial translocation and chronic immune activation (CIA) in successfully treated HIV-infected patients and to explore the mediating role of alpha-interferon in these processes.
Cross-sectional study nested in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients in South-Western France.
Patients initiated antiretroviral therapy between 2005 and 2008 and were treated with sustained virological suppression for at least two years. CIA was defined by the percentage of HLA-DR+/CD38+ among CD8+T-cells. Integrative analyses were performed using structural equation modelling (SEM).
The main analysis was performed in 57 HLA-A0201 positive patients, due to availability of percentages of actin-, vimentin-, lamin-specific CD8+T-cells (HLA-A2-restricted tests) to further characterize autoimmune response. Cytomegalovirus-induced response was assessed by Quantiferon and pp-65 ELISPOT. SEM revealed a direct effect of cytomegalovirus-induced response on CIA (standardized estimate βstd = 0.56, p-value = 0.0004). The effect of autoimmune-induced response on CIA was indirect through alpha-interferon pathway, assessed by expression levels of 5 alpha-interferon-stimulated genes ADAR, ISG15, IFIT1, Mx1 and OAS1 (effect of autoimmune response on alpha-interferon: βstd = 0.36, p-value = 0.0401; effect of alpha-interferon on CIA: βstd = 0.39, p-value = 0.0044). There was no direct effect of autoimmune-induced response on CIA (p-value = 0.3169). Microbial translocation as measured by 16SrDNA and sCD14 in plasma was not associated with CIA. Results were consistent in 142 patients in whom cytomegalovirus and auto-immunity responses were measured by Quantiferon and anti-nuclear antibodies, respectively. All analyses performed in HLA-A0201 positive patients and in the overall population revealed a significant effect of IFN-α latent variable on CIA.
The role of cytomegalovirus-induced response on CIA was confirmed as well as the involvement of alpha-interferon on CIA. The indirect effect of auto-immunity response on CIA revealed through the alpha-interferon pathway requires further investigation to confirm the potential role of auto-immunity for CIA in HIV-infected patients.
在成功接受治疗的HIV感染患者中，揭示巨细胞病毒诱导的反应、自身免疫诱导的反应、微生物易位与慢性免疫激活（CIA）之间的复杂关系，并探讨α干扰素在这些过程中的介导作用。
嵌套于ANRS CO3阿基坦队列的横断面研究，该队列是法国西南部一个以医院为基础的HIV-1感染患者前瞻性队列。
患者于2005年至2008年间开始接受抗逆转录病毒治疗，并接受持续病毒学抑制治疗至少两年。CIA通过CD8+T细胞中HLA-DR+/CD38+的百分比来定义。使用结构方程模型（SEM）进行综合分析。
由于可获得肌动蛋白、波形蛋白、层粘连蛋白特异性CD8+T细胞的百分比（HLA-A2限制性检测）以进一步表征自身免疫反应，因此对57名HLA-A*0201阳性患者进行了主要分析。通过定量干扰素和pp-65 ELISPOT评估巨细胞病毒诱导的反应。SEM显示巨细胞病毒诱导的反应对CIA有直接影响（标准化估计βstd = 0.56，p值 = 0.0004）。自身免疫诱导的反应对CIA的影响是通过α干扰素途径间接产生的，通过5种α干扰素刺激基因ADAR、ISG15、IFIT1、Mx1和OAS1的表达水平进行评估（自身免疫反应对α干扰素的影响：βstd = 0.36，p值 = 0.0401；α干扰素对CIA的影响：βstd = 0.39，p值 = 0.0044）。自身免疫诱导的反应对CIA没有直接影响（p值 = 0.
