Gomara M.J.,Unit of Synthesis and Biomedical Applications of Peptides IQAC CSIC |
Fernandez L.,Unit of Synthesis and Biomedical Applications of Peptides IQAC CSIC |
Perez T.,Unit of Synthesis and Biomedical Applications of Peptides IQAC CSIC |
Ercilla G.,Immunology Service |
Haro I.,Unit of Synthesis and Biomedical Applications of Peptides IQAC CSIC
Analytical Biochemistry | Year: 2010
The use of synthetic peptides of both structural and nonstructural proteins of GB virus C (GBV-C) has been studied for the development of new systems to diagnose infection caused by this virus. In an attempt to increase the antigenicity of linear peptide sequences, chimeric multiple antigenic peptides (MAPs) containing epitopes from E2, NS4, and NS5 GBV-C proteins have been synthesized. The synthetic constructs were evaluated by ELISA to establish whether the epitopes in chimeric branched peptides are more efficiently recognized by the specific antibodies compared to the monomeric linear sequences. Moreover, we have investigated the application of a commercial biosensor instrument for the detection of antibodies against the GBV-C in human serum samples. The results of the immunoassays reported in this work highlight the usefulness of synthetic tetrameric branched peptides containing sequences from envelope and nonstructural GBV-C proteins for the diagnosis of GBV-C infection. The potential clinical value of the MAP4(E2-NS5a) for the serodiagnosis of GBV-C infection was demonstrated, thus providing the basis for performing prevalence studies of the infection among the hemodialyzed and hepatitis C virus (HCV)-infected population. © 2009 Elsevier Inc. All rights reserved.
Bosca I.,Hospital Universitario La Paz |
Villar L.M.,Immunology Service |
Coret F.,Neurology Service |
Magraner M.J.,Hospital Universitario La Paz |
And 3 more authors.
Multiple Sclerosis | Year: 2010
The objective of this study was to investigate whether the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in cerebrospinal fluid (CSF) influences the response to treatment with beta-interferon in relapsing-remitting multiple sclerosis (RRMS) patients. We performed a collaborative prospective study including RRMS patients with brain MRI and LS-OCMB studies performed before starting interferon treatment. The primary endpoint was the risk of having a relapse after treatment initiation. Secondary endpoints included relapse rate, relapse-rate reduction, proportion of relapse-free patients and proportion of patients with sustained disability increase during follow-up. One-hundred and two patients were included. After a mean follow-up of 37.4 months, the risk of suffering a relapse was two-fold higher in patients with LS-OCMB (hazard ratio 2.0, 95% confidence interval 1.1-3.8). LS-OCMB+ patients showed lower reduction in relapse rate (51.8% versus 80.8%; p < 0.0001), higher relapse rate in the first year (0.8 versus 0.2; p = 0.001), lower proportion of relapse-free patients (25% versus 61.3%; p = 0.003), and higher proportion of patients with sustained 1.0 increase in the Expanded Disability Status Score (45% versus 12.9%; p = 0.0003). In conclusion, LS-OCMB can have an influence on the response to interferon treatment in RRMS patients. They could be used as a biological marker to predict high inflammatory activity after treatment.© 2010 The Author(s).Indications:39 patients with relapsing remitting multiple sclerosis.TypeofStudy:An open, multicenter study investigating whether the presence or absence of lipid-specific oligoclonal immunoglobulin M (IgM) bands (LS-OCMB) had an influence on the time to a new relapse, the proportion of relapse-free patients, and the disability progression during interferon (IFN) treatment (including Extavia), in patients with relapsing remitting multiple sclerosis (RRMS).Patients:102 patients, 28 males and 74 females, mean age 33.0 years; 39 were on Extavia, and 63 interferon beta 1a (44 Rebif and 19 Avonex); 40 LS-OCMB+ (13 males and 27 females, mean age 31.5 years), and 62 LS-OCMB- (15 males and 47 females, mean age 34.1 years). Follow-up: mean of 34.8 months.DosageDuration:Dosage not stated. Duration: mean of 34.8 months.Results:Results were given for the whole group of patients receiving IFN without separate data for Extavia. OCGB were present in 96.1% of the patients, OCMB in 46.1%, and LS-OCMB in 39.2%. 1 year after treatment initiation, only 5 patients had NAbs (2 LS-OCMB+ and 3 LS-OCMB-). No differences were noted in the incidence of NAbs between LS-OCMB+ and - patients. 53 patients suffered at least 1 relapse during treatment. The probability of having a relapse after treatment initiation was significantly higher for the LS-OCMB+ group, with a shorter time to relapse compared to LS-OCMB- patients. Among the variables for relapse, only the presence of LS-OCMB showed a higher risk of a second relapse. A significant reduction was noted in the relapse rate during the first year of IFN in both groups, although the reduction was lower in patients with LS-OCMB. These patients showed a higher relapse rate in the first year under treatment and the proportion of relapse-free patients was lower in the LS-OCMB+ group. After a mean follow-up of 34.8 months, higher EDSS score was noted in LS-OCMB+ patients. Patients lacking LS-OCMB remained stable during the study. The proportion of patients that increased in at least one point EDSS score during treatment was also higher for patients with LS-OCMB.AdverseEffects:No adverse events were mentioned.AuthorsConclusions:We think that our results have important clinical implications. LS-OCMB determination can help us to detect patients in which IFN treatment can be more effective (LS-OCMB-) and those at risk of an incomplete response (LS-OCMB+). Further research should be performed to investigate whether these patients would better benefit from other disease-modifying drugs since onset.FreeText:Primary endpoint: the time to first relapse after treatment initiation. Secondary endpoints: follow-up relapse rate, relapse-rate reduction, the proportion of relapse-free patients, mean Expanded Disability Status Scale (EDSS), and the proportion of patients with disability increase defined as ≥1.0 sustained increase in the EDSS (confirmed 3 months later) during follow-up. Tests: serum and cerebrospinal fluid levels of oligoclonal IgG band (OCGB), oligoclonal IgM bands (OCMB), and LS-OCMB; levels of neutralizing antibodies (NAbs); and magnetic resonance imaging. Concomitant drugs: steroids, given as high dose.
Ferraris J.R.,Pediatric Nephrology Service |
Ferraris J.R.,University of Buenos Aires |
Ferraris V.,Pediatric Nephrology Service |
Acquier A.B.,University of Buenos Aires |
And 4 more authors.
Clinical and Experimental Immunology | Year: 2015
Haemolytic uraemic syndrome (HUS) is characterized by haemolytic anaemia, thrombocytopenia and acute renal failure. We studied the activation state of classical and alternative pathways of complement during the acute phase of Shiga toxin-associated HUS by performing a prospective study of 18 patients and 17 age-matched healthy controls to evaluate C3, C3c, C4, C4d, Bb and SC5b-9 levels. SC5b-9 levels were increased significantly in all patients at admission compared to healthy and end-stage renal disease controls, but were significantly higher in patients presenting with oliguria compared to those with preserved diuresis. C3 and C4 levels were elevated significantly at admission in the non-oliguric group when compared to controls. No significant differences were found for C4d values, whereas factor Bb was elevated in all patients and significantly higher in oliguric patients when compared to both controls and non-oliguric individuals. A positive and significant association was detected when Bb formation was plotted as a function of plasma SC5b-9 at admission. Bb levels declined rapidly during the first week, with values not significantly different from controls by days 3 and 5 for non-oligurics and oligurics, respectively. Our data demonstrate the activation of the alternative pathway of complement during the acute phase of Stx-associated HUS. This finding suggests that complement activation may represent an important trigger for the cell damage that occurs during the syndrome. © 2015 British Society for Immunology.
Finiasz M.,Institute Investigaciones Hematologicas |
Otero C.,Institute Investigaciones Hematologicas |
Bezrodnik L.,Immunology Service |
Fink S.,Institute Investigaciones Hematologicas
Current Medicinal Chemistry | Year: 2011
Atopic asthma results from airway inflammation triggered by an environmental allergen. Symptoms include wheezing, dyspnea and cough, airway narrowing and/or hyperresponsiveness to several inhaled stimuli. Inflammation develops in a two-phase fashion. The first phase after exposure to the allergen consists of degranulation and release of both histamine and other stored preformed inflammatory mediators as well as newly synthesized ones, including cytokines, all of which increase mucus secretion and smooth muscle contraction. The second phase occurs later and lasts longer; it is due to different molecules: several cytokines and chemokines, arachidonic acid derivatives, enzymes such as metalloproteinases and cell adhesion molecules. Cytokines are key players in the chronic inflammation in asthma patients, but details on their role and interactions still remain undetermined. Recent evidence suggests that allergic asthma is a multifaceted condition actively controlled by effector as well as regulatory T cells (Tregs). T helper (Th) 2 cells and Th17 cells increase airway inflammation, while Tregs are anti-inflammatory. Cytokines are involved in the development and activation of all T cell subpopulations. They are also involved directly or indirectly in most approaches to asthma treatment. Several cytokines have been tested as therapeutic targets and some of the currently used therapies like corticosteroids, beta agonists and allergen immunotherapy affect cytokine production. The increased knowledge on cytokine interplay and lymphocyte subsets should generate new therapeutic strategies in the near future. © 2011 Bentham Science Publishers Ltd.
Sanmarti R.,Arthritis Unit |
Cabrera-Villalba S.,Arthritis Unit |
Gomez-Puerta J.A.,Arthritis Unit |
Ruiz-Esquide V.,Arthritis Unit |
And 5 more authors.
Journal of Rheumatology | Year: 2012
Objective. To analyze longterm progression to rheumatoid arthritis (RA) and the predictive value of anticitrullinated peptide/protein antibodies (ACPA) in palindromic rheumatism (PR). Methods. We selected all patients in our clinic with PR who had at least 1 ACPA measurement. We included only patients with pure PR, defined as no evidence of associated rheumatic disease at the first serum ACPA measurement. Clinical characteristics, serum ACPA levels, duration of PR until serum ACPA measurement, and total followup time were recorded. The outcome variable was the definitive diagnosis of RA. The prognostic value of ACPA status in pure PR for a definite diagnosis of RA was analyzed by different statistical methods. Results. Seventy-one patients (54 women/17 men) with a PR diagnosis were included. Serum ACPA were positive in 52.1%. After a mean followup of 7.6 ± 4.7 years since the first ACPA measurement, 24 patients (33.8%) progressed to chronic disease: 22% RA, 5.6% systemic lupus erythematosus, and 5.6% other diseases. The positive likelihood ratio of ACPA status for RA was 1.45, and the area under the receiver-operating characteristic curve of ACPA titers was 0.60 (95% CI 0.45-0.75). Progression to RA was more frequently seen in ACPA-positive than in ACPA-negative patients (29.7% vs 14.7%), but the difference was not significant (hazard ratio 2.46, 95% CI 0.77-7.86). Mean ACPA levels of patients with pure PR did not differ significantly from those of patients who progressed to RA. Conclusion. ACPA are frequently found in the sera of patients with PR, and a significant proportion of these patients do not progress to RA in the long term. The Journal of Rheumatology Copyright © 2012. All rights reserved.