IL-10 and IL-6/IL-10 as Predictive Biomarkers for treatment response in Non-infectious uveitis BRIEF RESEARCH REPORT

Rodrigo A Valenzuela^1,2Fabian Vega-Tapia²Nathaly Elizalde²Iván Esteban Flores²Felipe Rojas^3,4,5Annelise Goecke⁶Loreto Cuitino^2,4Cristhian A. Urzua^2,7,8*

• ¹Centro de Biomedicina, Universidad Mayor, Santiago, Chile
• ²Laboratory of Ocular and Systemic Autoimmune Diseases, Faculty of Medicine, University of Chile, Santiago, Chile
• ³Escuela de tecnología médica, Faculta de medicina, Universidad Andrés Bello, Santiago, Chile
• ⁴Servicio de Oftalmología, Hospital Clínico Universidad de Chile, Santiago, Chile
• ⁵Departamento de Tecnología Médica, Facultad de Medicina, Universidad de Chile, Santiago, Chile
• ⁶Rheumatology Section, Medicine Department, Hospital Clínico de la Universidad de Chile, Santiago, Chile
• ⁷Department of Ophthalmology, Faculty of Medicine, University of Chile, Santiago, Santiago Metropolitan Region (RM), Chile
• ⁸Facultad de Medicina Clinica Alemana, Universidad del Desarrollo, Santiago, Santiago Metropolitan Region (RM), Chile

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.