Browsing by Author "Burgos, Paula I."

Now showing 1 - 15 of 15
  • Thumbnail Image
    Item
    Association of IL4Rsingle-nucleotide polymorphisms with rheumatoid nodules in African Americans with rheumatoid arthritis
    (2010) Burgos, Paula I.; Causey, Zenoria L.; Tamhane, Ashutosh; Kelley, James M.; Brown, Elizabeth E.; Hughes, Laura B.; Danila, Maria I.; van Everdingen, Amalia; Conn, Doyt L.; Jonas, Beth L.
    Abstract Introduction To determine whether IL4R single-nucleotide polymorphisms (SNPs) rs1805010 (I50V) and rs1801275 (Q551R), which have been associated with disease severity in rheumatoid arthritis (RA) patients of European ancestry, relate to the presence of rheumatoid nodules and radiographic erosions in African Americans. Methods Two IL4R SNPs, rs1805010 and rs1801275, were genotyped in 749 patients from the Consortium for Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR) registries. End points were rheumatoid nodules defined as present either by physical examination or by chest radiography and radiographic erosions (radiographs of hands/wrists and feet were scored using the modified Sharp/van der Heijde system). Statistical analyses were performed by using logistic regression modeling adjusted for confounding factors. Results Of the 749 patients with RA, 156 (20.8%) had rheumatoid nodules, with a mean age of 47.0 years, 84.6% female gender, and median disease duration of 1.9 years. Of the 461 patients with available radiographic data, 185 (40.1%) had erosions (score >0); their mean age was 46.7 years; 83.3% were women; and median disease duration was 1.5 years. Patients positive for HLA-DRB1 shared epitope (SE) and autoantibodies (rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP)) had a higher risk of developing rheumatoid nodules in the presence of the AA and AG alleles of rs1801275 (odds ratio (OR)adj = 8.08 (95% confidence interval (CI): 1.60-40.89), P = 0.01 and ORadj = 2.97 (95% CI, 1.08 to 8.17), P = 0.04, respectively). Likewise, patients positive for the HLA-DRB1 SE and RF alone had a higher risk of developing rheumatoid nodules in presence of the AA and AG alleles of rs1801275 (ORadj = 8.45 (95% CI, 1.57 to 45.44), P = 0.01, and ORadj = 3.57 (95% CI, 1.18 to 10.76), P = 0.02, respectively) and in the presence of AA allele of rs1805010 (ORadj = 4.52 (95% CI, 1.20 to 17.03), P = 0.03). No significant association was found between IL4R and radiographic erosions or disease susceptibility, although our statistical power was limited by relatively small numbers of cases and controls. Conclusions We found that IL4R SNPs, rs1801275 and rs1805010, are associated with rheumatoid nodules in autoantibody-positive African-American RA patients with at least one HLA-DRB1 allele encoding the SE. These findings highlight the need for analysis of genetic factors associated with clinical RA phenotypes in different racial/ethnic populations.
  • Thumbnail Image
    Item
    Chemosensitizing Effect Of Nordihydroguaiaretic Acid (Ndga) And Its Tetra Acetylated Derivative (Ndgata) On Parental And Multiresistant Ta3 Mouse Mammary Adenocarcinoma Cell Lines
    (2008) Ferreira, Jorge; Pavani, Mario; Jana, Fabian; Burgos, Paula I.; Morello, Antonio; Maya, Juan Diego; Faúndez Cáceres, Mario; Lopez, Americo; De Ioannes I., Alfredo E.; Becker C., María Inés
  • Thumbnail Image
    Item
    Factors predictive of thrombotic events in LUMINA, a multi-ethnic cohort of SLE patients (LXXII)
    (OXFORD UNIV PRESS, 2010) Burgos, Paula I.; McGwin, Gerald, Jr.; Reveille, John D.; Vila, Luis M.; Alarcon, Graciela S.
    Method. SLE patients (ACR criteria), age epsilon 16 years, disease duration 5 years at enrolment (T0), African-American, Hispanic (Texan or Puerto Rican) or Caucasian ethnicity, from LUMINA, a longitudinal cohort, were studied. An event was defined as the presence of arterial or venous thrombosis. Time to the first thrombotic event was examined by univariable and multivariable (MV) Cox models adjusting for pertinent baseline clinical and socio-demographic variables.
  • Thumbnail Image
    Item
    First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus : Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR)
    (2018) Pons-Estel, Bernardo A.; Bonfa, Eloisa; Soriano, Enrique R.; Cardiel, Mario H.; Izcovich, Ariel; Popoff, Federico; Criniti, Juan M.; Vásquez, Gloria; Burgos, Paula I.; Llanos Muñoz, Carolina
  • No Thumbnail Available
    Item
    Hemicorea como primera manifestación clínica de lupus eritematoso sistémico
    (2017) Armstrong Bruzzone, Macarena; Iruretagoyena B., Mirentxu; Burgos, Paula I.
  • Thumbnail Image
    Item
    Inhibition of angiogenesis by platelets in systemic sclerosis patients
    (2015) Hirigoyen Pérez, Daniela María.; Burgos, Paula I.; Mezzano, Veronica.; Durán, Josefina; Barrientos, Magaly.; Sáez, Claudia G.; Panes Becerra, Olga Teresa; Mezzano, Diego; Iruretagoyena B., Mirentxu
    Abstract Introduction Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microvascular damage, inflammation, and fibrosis. It has become increasingly evident that platelets, beyond regulating hemostasis, are important in inflammation and innate immunity. Platelets may be an important source of proinflammatory and profibrotic cytokines in the vascular microenvironment. In this study, we sought to assess the contribution of platelet-derived factors in patients with SSc to the angiogenesis of human dermal microvascular endothelial cells (DMVECs) in a tubule formation assay and to characterize the secretion of profibrotic and proinflammatory cytokines in these platelets. Methods We analyzed platelets obtained from 30 patients with SSc and 12 healthy control subjects. Angiogenesis was evaluated in vitro with a DMVEC tubule formation assay on Matrigel and platelet-derived angiogenic factors such as vascular endothelial growth factor (VEGF), 165b isoform (VEGF165b), and cytokine secretion was evaluated. Platelet serotonin content was also determined. Results When DMVECs were incubated with SSc platelet releasates, tubule formation was significantly inhibited (p < 0.01, t test), and higher expression of endothelin-1 in these cells was observed compared with control subjects (p < 0.05, Mann–Whitney U test). In SSc platelet releasates, VEGF165b was significantly higher (p < 0.05, t test), and the VEGF165b/VEGF ratio was increased compared with that of control subjects. Higher secretion of transforming growth factor β (p < 0.01, t test) and CD40L (p < 0.01, t test) was observed compared with control subjects. Also, intraplatelet serotonin levels were lower in platelets obtained from patients with diffuse SSc compared with patients with limited SSc and control subjects (p < 0.05, t test). Conclusions Our findings suggest that antiangiogenic factors such as VEGF165b, together with proinflammatory and profibrotic factors secreted by platelets, can contribute to the progression of peripheral microvascular damage, defective vascular repair, and fibrosis in patients with SSc.Abstract Introduction Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microvascular damage, inflammation, and fibrosis. It has become increasingly evident that platelets, beyond regulating hemostasis, are important in inflammation and innate immunity. Platelets may be an important source of proinflammatory and profibrotic cytokines in the vascular microenvironment. In this study, we sought to assess the contribution of platelet-derived factors in patients with SSc to the angiogenesis of human dermal microvascular endothelial cells (DMVECs) in a tubule formation assay and to characterize the secretion of profibrotic and proinflammatory cytokines in these platelets. Methods We analyzed platelets obtained from 30 patients with SSc and 12 healthy control subjects. Angiogenesis was evaluated in vitro with a DMVEC tubule formation assay on Matrigel and platelet-derived angiogenic factors such as vascular endothelial growth factor (VEGF), 165b isoform (VEGF165b), and cytokine secretion was evaluated. Platelet serotonin content was also determined. Results When DMVECs were incubated with SSc platelet releasates, tubule formation was significantly inhibited (p < 0.01, t test), and higher expression of endothelin-1 in these cells was observed compared with control subjects (p < 0.05, Mann–Whitney U test). In SSc platelet releasates, VEGF165b was significantly higher (p < 0.05, t test), and the VEGF165b/VEGF ratio was increased compared with that of control subjects. Higher secretion of transforming growth factor β (p < 0.01, t test) and CD40L (p < 0.01, t test) was observed compared with control subjects. Also, intraplatelet serotonin levels were lower in platelets obtained from patients with diffuse SSc compared with patients with limited SSc and control subjects (p < 0.05, t test). Conclusions Our findings suggest that antiangiogenic factors such as VEGF165b, together with proinflammatory and profibrotic factors secreted by platelets, can contribute to the progression of peripheral microvascular damage, defective vascular repair, and fibrosis in patients with SSc.Abstract Introduction Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microvascular damage, inflammation, and fibrosis. It has become increasingly evident that platelets, beyond regulating hemostasis, are important in inflammation and innate immunity. Platelets may be an important source of proinflammatory and profibrotic cytokines in the vascular microenvironment. In this study, we sought to assess the contribution of platelet-derived factors in patients with SSc to the angiogenesis of human dermal microvascular endothelial cells (DMVECs) in a tubule formation assay and to characterize the secretion of profibrotic and proinflammatory cytokines in these platelets. Methods We analyzed platelets obtained from 30 patients with SSc and 12 healthy control subjects. Angiogenesis was evaluated in vitro with a DMVEC tubule formation assay on Matrigel and platelet-derived angiogenic factors such as vascular endothelial growth factor (VEGF), 165b isoform (VEGF165b), and cytokine secretion was evaluated. Platelet serotonin content was also determined. Results When DMVECs were incubated with SSc platelet releasates, tubule formation was significantly inhibited (p < 0.01, t test), and higher expression of endothelin-1 in these cells was observed compared with control subjects (p < 0.05, Mann–Whitney U test). In SSc platelet releasates, VEGF165b was significantly higher (p < 0.05, t test), and the VEGF165b/VEGF ratio was increased compared with that of control subjects. Higher secretion of transforming growth factor β (p < 0.01, t test) and CD40L (p < 0.01, t test) was observed compared with control subjects. Also, intraplatelet serotonin levels were lower in platelets obtained from patients with diffuse SSc compared with patients with limited SSc and control subjects (p < 0.05, t test). Conclusions Our findings suggest that antiangiogenic factors such as VEGF165b, together with proinflammatory and profibrotic factors secreted by platelets, can contribute to the progression of peripheral microvascular damage, defective vascular repair, and fibrosis in patients with SSc.
  • No Thumbnail Available
    Item
    Interferon-gamma ameliorates experimental autoimmune encephalomyelitis by inducing homeostatic adaptation of microglia
    (2023) Tichauer, Juan E.; Arellano, Gabriel; Acuna, Eric; Gonzalez, Luis F.; Kannaiyan, Nirmal R.; Murgas, Paola; Panadero-Medianero, Concepcion; Ibanez-Vega, Jorge; Burgos, Paula I.; Loda, Eileah; Miller, Stephen D.; Rossner, Moritz J.; Gebicke-Haerter, Peter J.; Naves, Rodrigo
    Compelling evidence has shown that interferon (IFN)-gamma has dual effects in multiple sclerosis and in its animal model of experimental autoimmune encephalomyelitis (EAE), with results supporting both a pathogenic and beneficial function. However, the mechanisms whereby IFN-gamma may promote neuroprotection in EAE and its effects on central nervous system (CNS)-resident cells have remained an enigma for more than 30 years. In this study, the impact of IFN-gamma at the peak of EAE, its effects on CNS infiltrating myeloid cells (MC) and microglia (MG), and the underlying cellular and molecular mechanisms were investigated. IFN-gamma administration resulted in disease amelioration and attenuation of neuroinflammation associated with significantly lower frequencies of CNS CD11b(+) myeloid cells and less infiltration of inflammatory cells and demyelination. A significant reduction in activated MG and enhanced resting MG was determined by flow cytometry and immunohistrochemistry. Primary MC/MG cultures obtained from the spinal cord of IFN-gamma-treated EAE mice that were ex vivo re-stimulated with a low dose (1 ng/ml) of IFN-gamma and neuroantigen, promoted a significantly higher induction of CD4(+) regulatory T (Treg) cells associated with increased transforming growth factor (TGF)-beta secretion. Additionally, IFN-gamma-treated primary MC/MG cultures produced significantly lower nitrite in response to LPS challenge than control MC/MG. IFN-gamma-treated EAE mice had a significantly higher frequency of CX3CR1(high) MC/MG and expressed lower levels of program death ligand 1 (PD-L1) than PBS-treated mice. Most CX3CR1(high)PD-L1(low)CD11b(+)Ly6G(-) cells expressed MG markers (Tmem119, Sall2, and P2ry12), indicating that they represented an enriched MG subset (CX3CR1(high)PD-L1(low) MG). Amelioration of clinical symptoms and induction of CX3CR1(high)PD-L1(low) MG by IFN-gamma were dependent on STAT-1. RNA-seq analyses revealed that in vivo treatment with IFN-gamma promoted the induction of homeostatic CX3CR1(high)PD-L1(low) MG, upregulating the expression of genes associated with tolerogenic and anti-inflammatory roles and down-regulating pro-inflammatory genes. These analyses highlight the master role that IFN-gamma plays in regulating microglial activity and provide new insights into the cellular and molecular mechanisms involved in the therapeutic activity of IFN-gamma in EAE.
  • Thumbnail Image
    Item
    Interplay between the autophagy-lysosomal pathway and the ubiquitin-proteasome system: a target for therapeutic development in alzheimer's disease
    (2018) Bustamante, H.; Gonzalez, A.; Cerda Troncoso, C.; Shaughnessy, Ronan Patrick; Otth, C.; Soza Gajardo, Andrea; Burgos, Paula I.
  • Thumbnail Image
    Item
    Latitude gradient influences the age of onset of rheumatoid arthritis: a worldwide survey
    (2017) Burgos, Paula I.; Ramos Remos, C.; Ramirez Gomez, A.; Brambila Barba, V.; Barajas Ochoa, A.; Castillo Ortiz, J. D.; Adebajo, A. O.; Espinoza, L. R.
  • Thumbnail Image
    Item
    Mestizos with systemic lupus erythematosus develop renal disease early while antimalarials retard its appearance : data from a Latin American cohort
    (2013) Pons-Estel, G.; Alarcón, G.; Burgos, Paula I.; Hachuel, L.; Boggio, G.; Wojdyla, D.; Massardo Vega, Loreto; Iglesias Gamarra, A.
  • Thumbnail Image
    Item
    Performance of the 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease in a Latin American Cohort
    (2024) Martin-Nares, Eduardo; Hernandez-Molina, Gabriela; Baenas, Diego Federico; Delgado de la Mora, Jesus; Caeiro, Francisco; Wurmann Kiblisky, Pamela; Pimentel-Quiroz, Victor R.; Ascuna Valdivia, Valery; Faz-Munoz, David; Saad, Emanuel Jose; Cairoli, Ernesto; Elgueta Pinochet, Sergio; Madariaga Charaja, Hugo; Montante-Montes de Oca, Daniel; Gallo, Jesica Romina; Ugarte-Gil, Manuel F.; Neira, Oscar; Burgos, Paula I.; Paira, Sergio
    Background/ObjectiveThe 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria (2019 AECC) for IgG4-related disease (IgG4-RD) is considered a significant advancement in the study of this condition. Most studies evaluating their performance have focused on White and Asian patients, leaving a knowledge gap regarding Latin American populations. Therefore, this study aimed to assess the performance of the 2019 AECC for IgG4-RD in a cohort of Latin American patients.MethodsA multicenter medical records review study was conducted, involving centers from Argentina, Chile, Mexico, Peru, and Uruguay. Data on IgG4-RD patients and mimicker conditions were collected through a standardized online form. The criterion standard for diagnosing IgG4-RD was based on the fulfillment of the Comprehensive Diagnostic Criteria for IgG4-RD and/or the Consensus Statement on Pathology. The 2019 AECC was retrospectively applied.ResultsWe included 300 patients, with 180 (60%) having IgG4-RD and 120 (40%) having mimicker conditions. The 2019 AECC had a sensitivity of 66.7% and a specificity of 100%. Sensitivity increased to 73.3% when disease-specific autoantibody items were removed, without affecting specificity. The true-positive cases had more involved organs, a higher availability of biopsy results, and were more likely to belong to the Mikulicz/systemic and proliferative phenotypes.ConclusionsThe use of the 2019 AECC for IgG4-RD in a Latin American population confirms its high specificity in excluding those without the disease. The presence of concomitant autoimmune diseases and clinically nonsignificant disease-specific autoantibodies excludes a significant number of patients from fulfilling the criteria.
  • Thumbnail Image
    Item
    Radiographic Severity of Rheumatoid Arthritis in African Americans: Results From a Multicenter Observational Study
    (WILEY-LISS, 2010) Bridges, S. Louis, Jr.; Causey, Zenoria L.; Burgos, Paula I.; Huynh, B. Quynh N.; Hughes, Laura B.; Danila, Maria I.; van Everdingen, Amalia; Ledbetter, Stephanie; Conn, Doyt L.; Tamhane, Ashutosh; Westfall, Andrew O.; Jonas, Beth L.; Callahan, Leigh F.; Smith, Edwin A.; Brasington, Richard; Moreland, Larry W.; Alarcon, Graciela S.; van der Heijde, Desiree M.
    Objective. To describe radiographic changes in African Americans with rheumatoid arthritis (RA) from the Consortium for the Longitudinal Evaluations of African Americans with Early Rheumatoid Arthritis (CLEAR) Registry, a multicenter observational study.
  • Thumbnail Image
    Item
    Smoking promotes exacerbated inflammatory features in dendritic cells of Chilean rheumatoid arthritis patients
    (2018) Prado, Carolina; Iruretagoyena B., Mirentxu; Burgos, Paula I.; Pacheco, Rodrigo
  • Thumbnail Image
    Item
    The prevalence of rheumatoid arthritis in Chile : a nationwide study performed as part of the national health survey
    (2020) Durán, Josefina; Massardo Vega, Loreto; Llanos Muñoz, Carolina; Iacobelli Gabrielli, Sergio Hernán; Burgos, Paula I.; Cisternas Martínez, Marcela Carolina; Iruretagoyena B., Mirentxu; Armstrong Bruzzone, Macarena; Aguilera Insunza, Raquel; Radrigán Araya, Francisco José Ricardo; Martínez Ruiz-Esquide, María Eugenia; Passi Solar, Alvaro Rodrigo; Vásquez Aravena, Nancy Margarita; Margozzini Maira, Paula; Riedemann, P.; Crisóstomo, N.; Cifuentes, C.; Hagedorn, L.; Cisternas, A.
  • Thumbnail Image
    Item
    Understanding the Cryoglobulinemias
    (2019) Fuentes, A.; Mardones, C.; Burgos, Paula I.