Browsing by Author "Massardo, L"
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- ItemA population based assessment of the use of orthopedic surgery in patients with rheumatoid arthritis(J RHEUMATOL PUBL CO, 2002) Massardo, L; Gabriel, SE; Crowson, CS; O'Fallon, WM; Matteson, ELObjective. To describe the use of orthopedic surgery, including joint replacement surgery, in a well defined population based cohort of patients with rheumatoid arthritis (RA) and to identify characteristics that predict such use.
- ItemAccuracy of anti-ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus - An international meta-analysis(WILEY, 2006) Karassa, FB; Afeltra, A; Ambrozic, A; Chang, DM; De Keyser, F; Doria, A; Galeazzi, M; Hirohata, S; Hoffman, IEA; Inanc, M; Massardo, L; Mathieu, A; Mok, CC; Morozzi, G; Sanna, G; Spindler, AJ; Tzioufas, AG; Yoshio, T; Ioannidis, JPAObjective. To quantitatively evaluate the diagnostic accuracy of antibodies to ribosomal P proteins (anti-P) for neuropsychiatric systemic lupus erythematosus (NPSLE) in general, for psychosis, mood disorder, or both, and for other diffuse manifestations.
- 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.
- ItemCirculating platelet-derived microparticles in systemic lupus erythematosus - Association with increased thrombin generation and procoagulant state(GEORG THIEME VERLAG KG, 2006) Pereira, J; Alfaro, G; Goycoolea, M; Quiroga, T; Ocqueteau, M; Massardo, L; Perez, C; Saez, C; Panes, O; Matus, V; Mezzano, DThe risk for thrombosis is significantly increased in systemic lupus erythematosus (SLE), affecting both venous and arterial vessels. Activated platelets are known to participate in thrombus formation and growth. A general feature of activated cells is the shedding of microparticles (MP) which support coagulation by exposure of negatively charged phospholipids and possibly tissue factor (TF). In this work we characterized circulating MP in patients with SLE and their relationship with a procoagulant state. Thirty patients with SLE (aged 15-72 years, mean age 38 years) and 20 healthy controls (aged 22-54 years, mean age 34 years) were studied; patients fulfilled 4 revised criteria for SLE. The number and cellular source of circulating MP were determined by flow cytometry using double labeling with specific monoclonal antibodies and annexin V. Thrombin generation was measured as the endogenous thrombin potential (ETP) without the addition of exogenous phospholipids and TF; under these conditions the generation of thrombin depended directly on the number of MP present in plasma. Thrombin anti-thrombin (TAT) and plasmin-antiplasmin (PAP) complexes were measured by ELISA. Compared to the controls, circulating MP were significantly elevated in the patient group (1218 +/- 136 vs 653 +/- 74 x 10(3)/ml plasma, p: 0.0007). In both groups, most of these MP were of platelet origin (927 +/- 131 vs 517 +/- 72 x 10(3)/ml plasma, p:0.009). ETP was higher among patients as compared to the controls (804 +/- 64 vs 631 +/- 37 nM thrombin, p: 0.025). Plasma levels of TAT in patients and controls were 3.4 +/- 0.8 and 1.4 +/- 0.5 mu g/L, respectively (p:0.04), and of PAP complexes were 62.5 +/- 14 and 24.05 +/- 2.5 mu g/ml, respectively (p:0.014). The number of platelet-derived MP correlated significantly with thrombin generation (r: 0.42; p: 0.038) and TAT levels (r: 0.40; p: 0.035). We did not find an association of circulating MP with disease activity nor with the presence of antiphospholipid antibodies. The increased number of circulating platelet-derived microparticles and their association with high ETP and activation of the coagulation system suggest that these microparticles play an important role in the pathogenesis of the prothrombotic state in SLE patients.
- ItemFamilial aggregation of systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases in 1,177 lupus patients from the GLADEL cohort(WILEY, 2005) Alarcon Segovia, D; Alarcon Riquelme, ME; Cardiel, MH; Caeiro, F; Massardo, L; Villa, AR; Pons Estel, BA; GLADELObjective. To determine whether there is familial aggregation of systemic lupus erythematosus (SLE) and/or other autoimmune diseases in SLE patients and to identify clinical differences between patients with and those without familial autoimmunity.
- 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.
- 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.
- 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.
- ItemPrevalence and isotype distribution of antiphospholipid antibodies in Chilean patients with systemic lupus erythematosus (SLE)(2001) Aguirre, V; Cuchacovich, R; Barria, L; Aris, H; Trejo, C; Massardo, L; Pasten, R; Espinoza, LPrevious studies have demonstrated that ethnicity plays a role in the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-beta (2) glycoprotein I (a beta (2)-GPI) antibodies in systemic lupus erythematosus (SLE) patients. Few studies have been done in Latin American populations. Serum samples from 129 Chilean SLE patients were tested for IgG, IgM and IgA aCL and a beta (2)-GPI by ELISA. Clinical data were reviewed with the focus on clinical manifestations of antiphospholipid syndrome (APS). Positivity for at least one isotype of aCL was found in 30% of patients, while only 10% were positive for at least one isotype of a beta (2)-GPI. IgG was the most prevalent isotype for aCL (16%), and the isotype distribution was similar (4%) for a beta (2)-GPI. In general, the presence of aCL was significantly associated with the presence of a beta (2)-GPI, but a number of samples were positive for only one antibody, some of them associated with clinical manifestations of APS. ACL antibodies at medium-high titers were significantly correlated with thrombosis (P=0.0007) and fetal loss (P=0.009); however, the sensitivity of a beta (2)-GPI for detecting thrombosis and fetal loss was lower than aCL (19 and 17% vs 56 and 50%, respectively), and the specificity slightly higher (91 and 90% vs 84 and 82%). In Chilean SLE patients, aCL and a beta (2)-GPI antibodies are important in the evaluation of patients with APS. However, the utility of a beta (2)-GPI antibodies was limited by the low prevalence of these antibodies in comparison with other ethnic groups. Further studies are needed to define the basis of the observed differences among ethnic groups.
- 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.