Iyer Jayant Venkatramani, Agrawal Rupesh, Yeo Tun Kuan, Gunasekeran Dinesh V, Balne Praveen Kumar, Lee Bernett, Au Veonice Bijin, Connolly John, Teoh Stephen C B
National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore; Singapore National Eye Center, Singapore.
National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore.
Cytokine. 2016 Aug;84:56-62. doi: 10.1016/j.cyto.2016.05.009. Epub 2016 May 27.
This study aims to perform comprehensive longitudinal immune factor analysis of aqueous humor in relation to the aqueous CMV viral load and systemic CD4 counts during treatment of patients with co-infection of HIV and CMVR.
Aqueous humor samples were collected from 17 HIV-positive patients with CMVR scheduled to undergo weekly intravitreal ganciclovir therapy as part of the prospective CMV Retinitis Intravitreal Ganciclovir Singapore Study (CRIGSS) over the course of 1year. Full data across all the 4 time points was obtained and analyzed for CMV DNA viral load, 41 cytokine and chemokine factors using real-time PCR with the FlexMAP 3D (Luminex®) platform and assessed using the Milliplex Human Cytokine® kit.
The following immune factors (Spearman correlation coefficient r value in parenthesis, p<0.05) showed strong correlation with CMV DNA load in the aqueous - MCP-1 (0.80, IFN-g (0.83), IP-10 (0.82), IL-8 (0.81), fractalkine (0.73), RANTES (0.68) - while the following showed moderate correlation - PDGF-AA (0.58), Flt-3L (0.59) and G-CSF (0.53). Only PDGF-AA revealed a statistically significant negative correlation with serum CD4 levels (r=-0.74).
Immune factors that correlate with intraocular CMV DNA load are identified. They are indicative of a Th1 and monocyte-macrophage mediated response, and exhibit a decreasing trend longitudinally through the course of treatment. These factors may be an important new consideration in individualizing the treatment of patients with CMVR.
本研究旨在对同时感染HIV和CMVR的患者在治疗期间，进行房水中免疫因子与房水巨细胞病毒（CMV）病毒载量及全身CD4细胞计数的全面纵向分析。
作为前瞻性新加坡玻璃体内更昔洛韦治疗巨细胞病毒性视网膜炎研究（CRIGSS）的一部分，在1年的时间里，从17例计划接受每周一次玻璃体内更昔洛韦治疗的HIV阳性CMVR患者中采集房水样本。获取所有4个时间点的完整数据，并使用FlexMAP 3D（Luminex®）平台通过实时PCR分析CMV DNA病毒载量、41种细胞因子和趋化因子，并使用Milliplex Human Cytokine®试剂盒进行评估。
以下免疫因子（括号内为Spearman相关系数r值，p<0.05）与房水中的CMV DNA载量呈强相关——单核细胞趋化蛋白-1（MCP-1）（0.80）、干扰素-γ（IFN-γ）（0.83）、干扰素诱导蛋白10（IP-10）（0.82）、白细胞介素-8（IL-8）（0.81）、 fractalkine（0.73）、调节激活正常T细胞表达和分泌的趋化因子（RANTES）（0.68）——而以下因子呈中度相关——血小板衍生生长因子-AA（PDGF-AA）（0.58）、Flt-3配体（Flt-3L）（0.59）和粒细胞集落刺激因子（G-CSF）（0.53）。只有PDGF-AA与血清CD4水平呈统计学显著负相关（r=-0.74）。
确定了与眼内CMV DNA载量相关的免疫因子。它们表明存在Th1和单核细胞-巨噬细胞介导的反应，并在治疗过程中纵向呈现下降趋势。这些因子可能是个体化治疗CMVR患者的一个重要新考虑因素。
