Valenzuela Rodrigo A, Vega-Tapia Fabian, Elizalde Nathaly, Flores Ivan, Rojas Felipe M, Goecke Annelise, Cuitino Loreto, Urzua Cristhian A
Laboratory of Ocular and Systemic Autoimmune Diseases, Faculty of Medicine, University of Chile, Santiago, Chile.
Laboratory of Vascular Immunopharmacology, Centro de Biomedicina, Universidad Mayor, Santiago, Chile.
Front Immunol. 2025 May 13;16:1584905. doi: 10.3389/fimmu.2025.1584905. eCollection 2025.
Uveitis, a group of heterogeneous diseases causing ocular inflammation, is a major contributor to vision loss globally. While systemic corticosteroids (CS) are the mainstay treatment, identifying CS-refractory patients remains a significant challenge. This study aimed to explore cytokine expression and Glucocorticoid Receptor (GR) levels as biomarkers for the early detection of CS-refractory cases in non-infectious uveitis. We assayed blood samples from 19 patients with non-infectious uveitis, for the expression of IL-6, IL-17A, TNF-α, IL-10 and GRα. The cohort included 11 refractory and 8 sensitive patients, categorized based on their clinical response to corticosteroids (prednisone 1 mg/kg/day). Blood draws were conducted at three time points (at baseline, day 7- and day 14 after CS initiation), and peripheral blood mononuclear cells (PBMCs) were isolated to measure cytokine and GRα transcript levels via real-time PCR. The expression levels of GRα and cytokines IL-6, IL-17A and TNF-α did not show significant changes between CS-sensitive and CS-refractory patients on the different days of treatment. However, IL-10 expression levels as the day14-to-day7 ratio were significantly higher in patients sensitive to CS therapy. A higher day14-to-day7 ratio was also found for the IL-6/IL-10, IL-17A/IL-10 and GRα/IL-10 ratios. ROC curve analysis demonstrated a robust predictive performance of IL-10 mRNA expression and the IL-6/IL-10 ratio for identifying CS-refractory patients. In conclusion, the expression of IL-10 and the IL-6/IL-10 ratio hold promise as early predictive biomarkers for CS treatment refractoriness in patients with non-infectious uveitis. These findings offer valuable insights into personalized treatment strategies, potentially leading to improved clinical outcomes.
葡萄膜炎是一组导致眼部炎症的异质性疾病,是全球视力丧失的主要原因。虽然全身用皮质类固醇(CS)是主要治疗方法,但识别对CS耐药的患者仍然是一项重大挑战。本研究旨在探索细胞因子表达和糖皮质激素受体(GR)水平作为非感染性葡萄膜炎中CS耐药病例早期检测的生物标志物。我们检测了19例非感染性葡萄膜炎患者血液样本中IL-6、IL-17A、TNF-α、IL-10和GRα的表达。该队列包括11例耐药患者和8例敏感患者,根据他们对皮质类固醇(泼尼松1mg/kg/天)的临床反应进行分类。在三个时间点(基线、CS开始后第7天和第14天)进行采血,并分离外周血单个核细胞(PBMC),通过实时PCR测量细胞因子和GRα转录水平。在治疗的不同天数,CS敏感和CS耐药患者之间GRα以及细胞因子IL-6、IL-17A和TNF-α的表达水平没有显著变化。然而,CS治疗敏感患者中IL-10表达水平的第14天与第7天比值显著更高。IL-6/IL-10、IL-17A/IL-10和GRα/IL-10比值的第14天与第7天比值也更高。ROC曲线分析表明,IL-10 mRNA表达和IL-6/IL-10比值在识别CS耐药患者方面具有强大的预测性能。总之,IL-10的表达和IL-6/IL-10比值有望作为非感染性葡萄膜炎患者CS治疗耐药性的早期预测生物标志物。这些发现为个性化治疗策略提供了有价值的见解,可能导致改善临床结果。