Browsing by Author "Jacobelli, S"
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- ItemAntibodies against galectin-8 in patients with systemic lupus erythematosus(SOC MEDICA SANTIAGO, 2006) Pardo, E; Carcamo, C; Massardo, L; Mezzano, V; Jacobelli, S; Gonzalez, A; Soza, ABackground: The family of lectins known as galectins (galectins 1-14) are involved in the regulation of the immune system and in oncogenesis. During a search for antigens recognized by antibodies produced by a patient with systemic lupus erythematosus described. Aim: To determine the frequency of autoantibodies against galectin-8 in lupus patients compared with healthy controls. Patients and Methods: Galectin-8 was purified from a bacterial expression system and used in immunoblot assays as antigen to screen the sera of 55 SLE patients and matched controls. Disease activity was evaluated using the Mexican Modification of the Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI). Results: Reactivity against galectin-8 was detected in 30% of SLE patients, compared to 7% ofcontrols (p = 0.003). We could not detect any particular SLE manifestation associated to the pressence of these autoantibodies. Conclusion: This is the first description of autoantibodies against galectin-8. Its higher frequency in a patients with SLE suggests a pathogenic role. Further studies are needed to determine their clinical relevance (Rev Med Chile 2006; 134: 159-66).
- ItemAntiribosomal P protein antibodies in Chilean SLE patients(2002) Massardo, L; Burgos, P; Martínez, ME; Pérez, R; Calvo, M; Barros, M; González, A; Jacobelli, SThe objective of this work was to determine the frequency and clinical associations of antiribosomal P protein antibodies (Anti-P) in a cohort of Chilean patients with systemic lupus erythematosus (SLE). Between 1996 and 1998, 141 consecutive patients with SLE,here examined prospectively according with a standard protocol. Disease activity was measured by MEX-SLEDAI in 138 patients. Anti-P positivity was determined by double immune diffusion or Western blot and ELISA. Anti-P was found in 21 (15%) patients, In the Anti-P positive patients recent onset SLE (disease duration of 1 year or less) was more frequent (P = 0.018). Anti-P was found in 73% of 83 patients with active SLE vs 4% of the 55 patients with inactive SLE (Yates corrected P = 0.00479). An association with anti-dsDNA antibodies by Farr assay was observed. Anti-P positive patients had a median Farr of 65IU/ml (1.4-1240) and Anti-P negative of 12IU/ml (1.4-992 P-value = 0.0084). During the study only two patients had lupus psychosis and they were Anti-P positive. No association,vas found with liver disease (six patients, two with Anti-P antibodies) or active glomerulonephritis (22 patients, four with Anti-P). Our data shows that the presence of Anti-P antibodies supports the clinical diagnosis of lupus psychosis.
- ItemAssociation of primary antiphospholipid syndrome with primary adrenal insufficiency(J RHEUMATOL PUBL CO, 1996) Gonzalez, G; Gutierrez, M; Ortiz, M; Tellez, R; Figueroa, F; Jacobelli, SThe association of primary adrenal insufficiency with antiphospholipid antibodies is usually reported in the context of adrenal thrombosis or hemorrhage. We describe a 35-year-old woman who developed a primary antiphospholipid syndrome (spontaneous abortion, thrombocytopenia, and cerebrovascular occlusion) in association with primary adrenal insufficiency without evidence of suprarenal hemorrhage or thrombosis.
- ItemCardiovascular risk factors in Chilean patients with rheumatoid arthritis(J RHEUMATOL PUBL CO, 2002) Cisternas, M; Gutierrez, MA; Klaassen, J; Acosta, AM; Jacobelli, SObjective. Epidemiologic studies have shown an increased mortality rate in patients with rheumatoid arthritis (RA). The most common cause of death in these patients is cardiovascular disease. We estimated the frequency of and examined risk factors for coronary artery disease in Chilean patients with RA.
- ItemCatastrophic antiphospholipid syndrome associated with crescentic glomerulonephritis(2000) Cisternas, M; Gutiérrez, MA; Rosenberg, H; Jara, A; Jacobelli, SThe association of renal failure with catastrophic antiphospholipid syndrome has been reported in the context of microvascular occlusions and/or malignant hypertension. We describe a 36-year-old woman who died of multiorgan failure with the laboratory, clinical and histopathological characteristics of catastrophic antiphospholipid syndrome associated with a crescentic glomerulonephritis and renal failure.
- ItemClinical features of Wegener granulomatosis and microscopic polyangiitis in Chilean patients(SOC MEDICA SANTIAGO, 2005) Cisternas, M; Soto, L; Jacobelli, S; Marinovic, MA; Vargas, A; Sobarzo, E; Saavedra, J; Chauan, K; Melendez, G; Foster, C; Pacheco, D; Wainstein, E; Sociedad Chilena de ReumatologiaBackground Systemic vasculitis are a group of heterogeneous diseases characterized by inflammation and necrosis of blood vessel walls. The etiology is not known, but geographic and environmental, factors are implicated. Aim: To describe the clinical features of microscopic polyangiitis (MPA) and Wegener's granulomatosis (WG) in a Chilean cohort of patients. Patients and methods: Retrospective review of the medical records of 123 patients with the diagnosis of systemic vasculitis (65 MPA and 58 WG), seen from 1990 to 2001. The diagnosis were made based on the American College of Rheumatology and Chapel Hill criteria. Results: The mean follow-up for MPA was 15 months (1-120) and for WG, 20 months (1-120). The median age (years) at diagnosis for MPA was 61 (19-82) and WG 50 (20-82). Gender distribution was similar in both groups (male: 68% and 57% respectively). The main clinical features in the MPA group were renal involvement (68%), peripheral nervous system involvement (57%), pulmonary hemorrhage (28%), and skin disease (32%). In the WG group were alveolar hemorrhage (62%), renal involvement (78%); paranasal sinus involvement (57%); and ocular disease (26%). In both, creatinine levels above 2.0 mg/dl were associated with a higher mortality (p < 0.01). ANCA by immunofluorescence was performed in 56 MPA patients (75% had pANCA, 4% had cANCA and 21% were ANCA negative) and in 55 WG patients (17%, had pANCA, 79% had cANCA and 4% were ANCA negative). Global mortality was 18% and 17% respectively, and the most causes of death were infections. Conclusions: The clinical features of our patients are similar to other-published data. In our WG and MPA patients the main predictor for death was a serum creatinine above 2 mg/dl.
- ItemGalectin-8 binds specific beta 1 integrins and induces polarized spreading highlighted by asymmetric lamellipodia in Jurkat T cells(ELSEVIER INC, 2006) Carcamo, C; Pardo, E; Oyanadel, C; Bravo Zehnder, M; Bull, P; Caceres, M; Martinez, J; Massardo, L; Jacobelli, S; Gonzalez, A; Soza, AIntegrin-mediated encounters of T cells with extracellular cues lead these cells to adhere to a variety of substrates and acquire a spread phenotype needed for their tissue incursions. We studied the effects of galectin-8 (Gal-8), beta-galactoside binding lectin, on Jurkat T cells. Immobilized Gal-8 bound alpha 1 beta 1 and alpha 5 beta 1 but not alpha 2 beta 1 and alpha 4 beta 1 and adhered these cells with similar kinetics to immobilized fibronectin (FN). Function-blocking experiments with monoclonal anti-integrin antibodies suggested that alpha 5 beta 1 is the main mediator of cell adhesion to this lectin. Gal-8, but not FN, induced extensive cell spreading frequently leading to a polarized phenotype characterized by an asymmetric lamellipodial protrusion. These morphological changes involved actin cytoskeletal rearrangements controlled by PI3K, Rac-1 and ERK1/2 activity. Gal-8-induced Rac-1 activation and binding to alpha 1 and alpha 5 integrins have not been described in any other cellular system. Strikingly, Gal-8 was also a strong stimulus on Jurkat cells in suspension, triggering ERK1/2 activation that in most adherent cells is instead dependent on cell attachment. In addition, we found that patients with systemic lupus erythematosus (SLE), a prototypic autoimmune disorder, produce Gal-8 autoantibodies that impede both its binding to integrins and cell adhesion. These are the first function-blocking autoantibodies reported for a member of the galectin family. These results indicate that Gal-8 constitutes a novel extracellular stimulus for T cells, able to bind specific beta 1 integrins and to trigger signaling pathways conducive to cell spreading. Gal-8 could modulate a wide range of T cell-driven immune processes that eventually become altered in autoimmune disorders. (C) 2005 Elsevier Inc. All rights reserved.
- ItemHypothalamic-pituitary-adrenal axis function and prolactin secretion in systemic lupus erythematosus(STOCKTON PRESS, 1998) Gutierrez, MA; Garcia, ME; Rodriguez, JA; Rivero, S; Jacobelli, SThe objective was to study the response of cortisol and of prolactin (PRL) to specific stimuli in systemic lupus erythematosus (SLE). We measured the response of cortisol to insulin-induced hypoglycemia and of PRL to thyrotropin releasing hormone (TRH) in seven patients with active untreated SLE and in ten paired control subjects. All were women with regular menstrual cycles. With the exception of two patients, they had never received corticosteroids before the study.
- ItemHypothalamic-pituitary-adrenal axis function in patients with active rheumatoid arthritis(1999) Gutiérrez, MA; García, ME; Rodríguez, JA; Mardonez, G; Jacobelli, S; Rivero, SObjective. To study the response of cortisol and of prolactin (PRL) to specific stimuli in rheumatoid arthritis (RA).
- ItemIncreased expression of c-rel, from the NF-κB/Rel family, in T cells from patients with systemic lupus erythematosus(2000) Burgos, P; Metz, C; Bull, P; Pincheira, R; Massardo, L; Errázuriz, C; Bono, MR; Jacobelli, S; González, AObjective. To explore the role of the NF-kappa B/Rel transcription factor family in autoimmunity, we investigated whether peripheral blood mononuclear cells (PBMC) and T cells from the blood of patients with systemic lupus erythematosus (SLE) exhibit abnormal expression of c-rel, both when recently isolated and/or during in vitro activation.
- ItemInfluence of the HLA-DR beta shared epitope on susceptibility to and clinical expression of rheumatoid arthritis in Chilean patients(1997) Gonzalez, A; Nicovani, S; Massardo, L; Aguirre, V; Cervilla, V; Lanchbury, JS; Jacobelli, SObjective - To analyse the influence of shared epitope positive HLA-DRB1 alleles (QKRAA or QRRAA)) on rheumatoid arthritis (RA) susceptibility and severity in Chileans, a population that exhibits a weak association with HLA-DR4.
- ItemLong-Term outcome of type V lupus membranous glomerulonephritis(SOC MEDICA SANTIAGO, 2005) Pasten, R; Massardo, L; Rosenberg, H; Radrigan, F; Roessler, E; Valdivieso, A; Jacobelli, SBackground: The long-term outcome of the pure form of WHO type V lupus membranous glomerulonephritis is apparently more benign than that of other forms of lupus glomerulonepbritis. However 12% of such patients progress to terminal renal failure. The presence of proteinuria may be an indication of cytotoxic agents. Aim: To study the clinical long-term outcome of WHO type V Inpus membranous glomerulonepbritis. Material and methods: A retrospective analysis of all kidney biopsies of a University Pathology Department, with the diagnosis of WHO type V lupus membranous glomerulonephritis. Review of medical records of patients with the disease and one clinical assessment of all living patients. Results: Between 1973 and 2000, 703 kidney biopsies were done to patients with systemic lupus erytbematosus. Of these, 40 were membranous glomerulonepbritis and in 33 patients (28 women, age range 6-71 years), data on the evolution and survival was obtained. Nineteen bad type Va and the rest type Vb nephritis. Two presented with renal failure and I I with proteinuria over 3.5 g/24h. The median follow-up since the renal biopsy was 63 months (range 1-316). At the end of follow-up, four bad a creatinine clearance of less then 15 ml/h and four a clearance between 15 and 29 ml/h (one of these received a renal allograft). Eleven (33016) patients had died, mostly due to infections. Life expectancy at five years with a creatinine clearance over 15 ml/h was 75%. Bad prognostic factors were an elevated creatinine clearance over 15 ml/h was 75%. Bad prognostic factors were an elevated creatinine and high blood pressure at the moment of the biopsy. Conclusions: The clinical outcome of these patients was bad. Twelve percent reached a stage of terminal renal failure. This is in contrast with the 3% progression to a similar stage of proliferalive glomerulonephritis treated with the 3% cycloposphamide. New tberapies for this condition must be sought.
- ItemLymphoid B cells induce NF-kappa B activation in high endothelial cells from human tonsils(OXFORD UNIV PRESS, 2006) Naves, R; Reyes, LI; Rosemblatt, M; Jacobelli, S; Gonzalez, A; Bono, MRImmune surveillance depends on still poorly understood lymphocyte-endothelium interactions required for lymphocyte transendothelial migration into secondary lymphoid organs. The nuclear factor kappa B (NF-kappa B) regulatory system and its inhibitory I kappa B proteins control the inducible expression of adhesion molecules, cytokines and chemokines involved in endothelial activation and lymphocyte transmigration. Here we present results showing the activation of this system in response to the interaction of high endothelial cells from human tonsils (HUTEC) with human B and T lymphoid cell lines and primary tonsillar lymphocytes. Western blot and electrophoretic mobility shift assays show that adhesion of different lymphoid cells induce varying levels of NF-kappa B activation in HUTEC, with Daudi cells, tonsil-derived B cell line 10 (TBCL-10) and primary tonsillar B lymphocytes causing the strongest activation. The main NF-kappa B protein complexes translocated to the nucleus were p65/p50 and p50/p50. Results from reverse transcription-PCR and flow cytometry analysis of HUTEC indicate that the interaction with Daudi cells induce an increased expression of IL-6 and IL-8 mRNA and cell-surface expression of intercellular adhesion molecule-1, all of which were prevented by sodium salicylate, an inhibitor of NF-kappa B activation. Transwell experiments show that NF-kappa B activation and the response of HUTEC to the interaction of Daudi cells does not depend on direct cell-cell contact but rather on the production of soluble factors that require the presence of both cell types. These results suggest that lymphocytes and high endothelium establish a cross talk leading to NF-kappa B-mediated expression of cytokines and adhesion molecules, inducing endothelial cell activation.
- ItemOccasional series: Lupus around the world - The Chilean experience of systemic lupus erythematosus(1996) Massardo, L; Jacobelli, SThe Chilean experience with SLE began more than 40 years ago. The first series was published in 1958 with 108 patients. Lupus hair was described for the first time as a symptom that highly suggested SLE at that time. Subsequent studies have dealt with different clinical aspects of the disease. The description of silent nephropathy in SLE and inspiratory muscle dysfunction as a cause of unexplained dyspnoea have been relevant contributions to the understanding of this condition. Patient survival has improved over the last decades from 13% at 5 years in 1959 up to 87% in 1994. Reasons for this improved survival are probably related to better diagnosis and management of the severely ill patients. However, in spite of this, the incidence of infections in our patients often contributes to fatal outcome. Recently, some studies have been published related to the basic pathogenic mechanisms of this disease.
- ItemOutcome of Chilean patients with lupus nephritis and response to intravenous cyclophosphamide(2003) Velásquez, X; Verdejo, U; Massardo, L; Martínez, ME; Arriagada, S; Rosenberg, H; Valdivieso, A; Jacobelli, SSeveral recent open studies suggest that the response rates of lupus nephritis to intravenous (IV) cyclophosphamide are lower than those observed in clinical trials. One explanation could be ethnic differences; for example, black patients more frequently have treatment-resistant lupus nephritis. Another could be the inclusion of patients who are noncompliant with therapy. From our register of 268 systemic lupus erythematosus (SLE) patients examined between 1973 and 1996, 61 patients were treated for proliferative lupus nephritis (17 had World Health Organization [WHO] type III and 43 had WHO type IV) and were followed through to 2001. Exclusion criteria included a serum creatinine level >3 mg/dL. In this retrospective study, we assessed renal outcome and survival with an endpoint of end-stage renal disease (ESRD) or death (Kaplan-Meier). In the univariate analysis, worse prognostic factors for survival were serum creatinine >1.3 mg/dL (p < 0.001), age <30 years (p < 0.001), class 2 renal function stage (p < 0.03), and renal biopsy activity index >7 (p < 0.02). In the subgroup of 26 patients treated with IV cyclophosphamide, survival at 5 and 10 years was 82% and 73%, respectively. The dosage of IV cyclophosphamide was slightly lower than usual and used for a shorter period (median = 23 months) than what is usually recommended because of the high frequency of complications. Renal outcome of the IV cyclophosphamide-treated patients was poorer than that reported in the National Institutes of Health series (ESRD: 15% versus 3%). This low survival rate could reflect the short course and lower doses of IV cyclophosphamide used or ethnic differences. These data emphasize the need for continuous research for better-tolerated drug schemes for treatment of our lupus nephritis patients.
- ItemThe presence of the HLA-DRB1 shared epitope correlates with erosive disease in Chilean patients with rheumatoid arthritis(OXFORD UNIV PRESS, 2002) Massardo, L; Gareca, N; Cartes, MA; Cervilla, V; Gonzalez, A; Jacobelli, SObjective. To assess the contribution of the HLA-DRB1 shared epitope (SE) to the radiological outcome of rheumatoid arthritis (RA) after 6 yr of follow-up in a reported series of 129 Chilean patients with established disease.