Universidad del Desarrollo

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Enhanced mTORC1 Signaling in Inflammatory Monocytes Links Systemic Inflammation to Cardiovascular Disease in Rheumatoid Arthritis
(MDPI AG, 2025-10-22)
Karsulovic, Claudio
;
Fabian Tempio
;
Mercedes Lopez
;
Julia Guerrero
;
Ka Wei Katty Joo Hu
Objectives: Cardiovascular disease (CVD) is the leading cause of mortality in patients with rheumatoid arthritis (RA), not fully explained by traditional risk factors and disease activity alone. This study explored the relationship between circulating monocyte subsets, inflammatory cytokine profiles, and Mammalian Target of Rapamycin Complex (mTORC) signaling in RA patients with and without a history of CVD. Methods: Peripheral blood mononuclear cells from 9 RA patients with prior CVD, 9 carefully matched RA controls without CVD, and 6 healthy controls were analyzed by flow cytometry. Matching was rigorously conducted across clinically relevant variables, including age, sex, blood pressure, lipid profile, smoking status, RA duration, disease activity, Disease-Modifying Anti-Rheumatic Drug (DMARD) failures, and steroid use. Monocyte subsets were classified as inflammatory (CD14+HLA-DR+CCR2+) and non-inflammatory (CD14+CD163+CCR2−). Results: RA-CVD+ patients exhibited higher frequencies of inflammatory monocytes and elevated intracellular levels of Interleukin 1 β (IL-1β) and Interleukin 6 (IL-6) compared to RA-CVD− patients and healthy controls. mTORC activation, assessed by phosphorylation of S6 Ribosomal Protein (S6Rp), was significantly increased in inflammatory monocytes from RA-CVD+ patients. Conclusions: S6Rp correlated with IL-1β and IL-6 levels only in the RA-CVD+ group, suggesting a link between mTORC activity and inflammatory monocyte function. Notably, these inflammatory features did not correlate with disease activity scores or disease duration. We observed increased mTORC1 signaling in inflammatory monocytes in RA-CVD+ patients, suggesting a potential association with cardiovascular comorbidity.</jats:p>
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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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Enfermedad relacionada a IgG4. Serie clínica de pacientes chilenos
(2022)
María C. Cuéllar
;
Miguel Gutiérrez
;
Alejandra Herrera
;
Fabián Elgueta
;
Pamela Wurmann
Scopus© Citations 1 4
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Clinical and Serological Features in Latin American IgG4-Related Disease Patients Differ According to Sex, Ethnicity, and Clinical Phenotype
(2022)
Eduardo Martín-Nares
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Diego Federico Baenas
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María Carolina Cuellar Gutiérrez
;
Gabriela Hernández-Molina
;
Alberto Christian Ortiz
Scopus© Citations 12 6
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A consensus of the Chilean Nephrology and Rheumatology Societies on renal involvement in systemic lupus
(2015)
Verónica Aguirre
;
Miriam Alvo
;
Leopoldo Ardiles
;
J. Daniel Carpio
;
Carolina Foster
4 1Scopus© Citations 3
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Renal involvement in antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides. Recommendations of the Chilean Societies of Nephrology and Rheumatology
(2018)
Verónica Aguirre
;
Miriam Alvo
;
Leopoldo Ardiles
;
Alberto Fierro
;
Annelise Goecke
9 1
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Glucocorticoid Receptor-alpha and MKP-1 as Candidate Biomarkers for Treatment Response and Disease Activity in Vogt-Koyanagi-Harada Disease
(2019)
Cristhian A. Urzua
;
Ping Chen
;
Benjamin Chaigne-Delalande
;
Baoying Liu
;
Rodrigo Anguita
42Scopus© Citations 5

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