L&T Department of Ocular Pathology, Vision Research Foundation, Chennai, India.
Centre for Biotechnology, Anna University, Chennai, India.
Ocul Immunol Inflamm. 2023 Apr;31(3):566-575. doi: 10.1080/09273948.2022.2106247. Epub 2022 Aug 10.
Notwithstanding well-established clinical features of Immune Recovery Uveitis (IRU), specific diagnostic tools to identify at-risk patients are lacking. Identification of biomarkers for IRU prediction can allow high-risk patients to benefit from specific preventive strategies, development of therapies, and elucidate immune reconstitution associated pathogenesis.
HIV+ patients were classified into four groups (A, B, C and D) with and without ocular manifestations, with follow-up over a year. Patients' ocular parameters were examined and manifestations like uveitis and IRU noted. Selected miRNAs were investigated in PBMCs by using miRNA PCR assay. Bioinformatic analysis used miRNet to predict the targets of miRNA-192-5p and miRNA-543 and KOBAS for pathways.
Hsa-miR-192-5p and hsa-miR-543 levels were measured by qPCR using RNA isolated from PBMCs of HIVinfected patients. Hsa-miR-192-5p and hsa-miR-543 were down regulated in patients exhibiting ocular manifestations. Our results showed hsa-miR-192-5p (Group B vs D p 0.007) and hsa-miR-543 levels in PBMCs reliably distinguish between HIV patients diagnosed with IRU. Both miRNAs target multiple genes involved in inflammatory pathways as predicted by bioinformatic analysis.
Decreased expression levels of miRNA-192 in patients with ocular manifestations and IRU, could facilitate identification of the status of the disease in HIV patients.
尽管免疫恢复性葡萄膜炎 (IRU) 的临床特征已经得到充分证实,但缺乏识别高危患者的特定诊断工具。识别用于预测 IRU 的生物标志物可以使高危患者受益于特定的预防策略、治疗方法的开发,并阐明与免疫重建相关的发病机制。
将 HIV+ 患者分为有和无眼部表现的 A、B、C 和 D 四组,并进行一年以上的随访。检查患者的眼部参数并记录葡萄膜炎和 IRU 等表现。通过 miRNA PCR assay 检测 PBMCs 中的选定 miRNA。使用 miRNet 进行生物信息学分析以预测 miRNA-192-5p 和 miRNA-543 的靶标,并用 KOBAS 进行通路分析。
使用 qPCR 测量了从 HIV 感染患者的 PBMCs 中分离出的 RNA 中的 hsa-miR-192-5p 和 hsa-miR-543 水平。在出现眼部表现的患者中,hsa-miR-192-5p 和 hsa-miR-543 下调。我们的结果表明,hsa-miR-192-5p(B 组与 D 组相比,p 0.007)和 hsa-miR-543 在 PBMCs 中可以可靠地区分诊断为 IRU 的 HIV 患者。两种 miRNA 的水平都可以预测生物信息学分析中炎症途径涉及的多个基因的靶标。
眼部表现和 IRU 患者中 miRNA-192 的表达水平降低,可能有助于识别 HIV 患者的疾病状态。