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IL-10 and IL-6/IL-10 as predictive biomarkers for treatment response in non-infectious uveitis
(Frontiers Media SA, 2025-05-13)
Rodrigo A. Valenzuela
;
Fabian Vega-Tapia
;
Nathaly Elizalde
;
Ivan Flores
;
Felipe M. Rojas
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.
Scopus© Citations 6 1
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Non-Infectious Uveitis and Pregnancy, is There an Optimal Treatment? Uveitis Course and Safety of Uveitis Treatment in Pregnancy
(2024)
Magdalene Yin Lin Ting
;
Fabian Vega-Tapia
;
Rodrigo Anguita
;
Loreto Cuitino
;
Rodrigo A. Valenzuela
Scopus© Citations 2 7
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Combination of infrared reflectance and OCT imaging for age-related macular degeneration screening via deep learning
(2023)
URZUA SALINAS, CRISTHIAN
;
Felipe Salgado
;
Loreto Cuitino
;
Carla Vairetti
;
Fabián Vega Tapia
10
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miRNA Landscape in Pathogenesis and Treatment of Vogt–Koyanagi–Harada Disease
(2021)
Fabian Vega-Tapia
;
Mario Bustamante
;
Rodrigo A. Valenzuela
;
Cristhian A. Urzua
;
Loreto Cuitino
<jats:p>miRNAs, one of the members of the noncoding RNA family, are regulators of gene expression in inflammatory and autoimmune diseases. Changes in miRNA pool expression have been associated with differentiation of CD4<jats:sup>+</jats:sup> T cells toward an inflammatory phenotype and with loss of self-tolerance in autoimmune diseases. Vogt–Koyanagi–Harada (VKH) disease is a chronic multisystemic pathology, affecting the uvea, inner ear, central nervous system, and skin. Several lines of evidence support an autoimmune etiology for VKH, with loss of tolerance against retinal pigmented epithelium-related self-antigens. This deleterious reaction is characterized by exacerbated inflammation, due to an aberrant T<jats:sub><jats:italic>H</jats:italic></jats:sub>1 and T<jats:sub><jats:italic>H</jats:italic></jats:sub>17 polarization and secretion of their proinflammatory hallmark cytokines interleukin 6 (IL-6), IL-17, interferon γ, and tumor necrosis factor α, and an impaired CD4<jats:sup>+</jats:sup> CD25<jats:sup><jats:italic>high</jats:italic></jats:sup> FoxP3<jats:sup>+</jats:sup> regulatory T cell function. To restrain inflammation, VKH is pharmacologically treated with corticosteroids and immunosuppressive drugs as first and second line of therapy, respectively. Changes in the expression of miRNAs related to immunoregulatory pathways have been associated with VKH development, whereas some genetic variants of miRNAs have been found to be risk modifiers of VKH. Furthermore, the drugs commonly used in VKH treatment have great influence on miRNA expression, including those miRNAs associated to VKH disease. This relationship between response to therapy and miRNA regulation suggests that these small noncoding molecules might be therapeutic targets for the development of more effective and specific pharmacological therapy for VKH. In this review, we discuss the latest evidence regarding regulation and alteration of miRNA associated with VKH disease and its treatment.</jats:p>
4Scopus© Citations 7
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New Pharmacological Strategies for the Treatment of Non-Infectious Uveitis. A Minireview
(2020)
Rodrigo A. Valenzuela
;
Iván Flores
;
Beatriz Urrutia
;
Francisca Fuentes
;
Pablo E. Sabat
Scopus© Citations 28 2
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Definition of Uveitis Refractory to Treatment: A Systematic Review in the Absence of a Consensus
(2020)
Rodrigo A. Valenzuela
;
Iván Flores
;
Myriam Pujol
;
Carolina Llanos
;
Ester Carreño
3Scopus© Citations 10
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Initial-onset acute and chronic recurrent stages are two distinctive courses of Vogt-Koyanagi-Harada disease
(2020)
URZUA SALINAS, CRISTHIAN
;
Carl Herbort
;
Rodrigo A. Valenzuela
;
Ahmed M. Abu El-Asrar
;
Lourdes Arellanes-Garcia
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>To describe distinctive stages of Vogt-Koyanagi-Harada (VKH) disease: initial-onset acute versus chronic recurrent disease.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>A comprehensive literature review regarding stages and clinical presentations of VKH disease was conducted.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Despite a list of signs that has been described as characteristic features of early or late phases of VKH disease, the current classification -developed by an international committee and published in 2001- does not consider a distinction regarding the time from onset of disease symptoms, and specific findings observed at certain time point from the symptoms presentation and outcomes related to the stage of VKH disease. In that sense, chronic recurrent VKH disease is more refractory to treatment and is associated with a higher rate of complications. Accordingly, this subset of VKH patients has poorer functional and anatomical outcomes than patients with an initial-onset acute disease.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>An early clear distinction of VKH phenotype [Initial-onset acute versus chronic recurrent disease] should be considered in each clinical scenario, evaluating the delay in diagnosis and the clinical presentation, since it may help clinicians to perform a correct disease prognosis categorization and thus to make treatment decisions in terms of potential refractoriness or expected clinical outcomes.</jats:p> </jats:sec>
Scopus© Citations 25 1

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