Publications (11)38.57 Total impact
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Article: Development of poly(anhydride) nanoparticles loaded with peanut proteins: The influence of preparation method on the immunogenic properties.
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ABSTRACT: Allergen-specific immunotherapy is based on the administration of allergens with the main disadvantage of inducing an allergic reaction. Within this context, we report the generation of an adjuvant and allergen-delivery system for peanut allergen immunotherapy with reduced IgE induction. Therefore, we prepared and characterized poly(anhydride) nanoparticles loaded with peanut proteins using the solvent displacement method, with some modifications in the manufacturing process. The precipitation of polymer was performed with either a mixture of ethanol and water or water. The resultant nanoparticles were dried by either freeze-drying or spray-drying, respectively. Poly(anhydride) nanoparticles loaded with peanut proteins were successfully developed, achieving both high encapsulation efficiency (70-80%) and manufacturing yield (60-80%). After intradermal immunization of mice (C57Bl/6) with peanut proteins incorporated into poly(anhydride) nanoparticles, a strong mixed T(H)1/T(H)2-type immune response was observed. Furthermore, we also provide, to our knowledge for the first time, clear evidence of the influence of formulation design on the immunostimulatory properties of nanoparticles. Taken together, our findings indicate that poly(anhydride) nanoparticles are efficient stimulators of immune responses and promising adjuvants and allergen-delivery systems applied for immunotherapy.European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 07/2012; 82(2):241-9. · 3.15 Impact Factor -
Article: Two patients with anaphylactic shock due to fosfomycin.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 03/2011; 106(3):260-1. · 2.83 Impact Factor -
Article: Selective allergic reactions to clavulanic acid: a report of 9 cases.
The Journal of allergy and clinical immunology 04/2010; 126(1):177-9. · 9.17 Impact Factor -
Article: In vitro diagnosis of anaphylaxis.
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ABSTRACT: The application and development of new in vitro techniques aims to enable a diagnosis to be reached while incurring no risk for the patient, a situation which is particularly desirable in the case of severe reactions like anaphylaxis. The in vitro diagnosis of anaphylaxis includes, among other aspects, the serial measurement of mediators which are released in the course of an anaphylactic reaction such as tryptase, histamine, chymase, carboxypeptidase A3, platelet-activating factor and other products from mastocytes. The detection of agents which trigger the anaphylactic reaction can be made with the use of serologic methods: serum-specific IgE or with cellular tests which measure the release of basophil mediators (leukotrienes, histamine) or with the analysis of the expression of basophil markers, a technique known as the basophil activation test. These techniques offer interesting alternatives in the diagnosis of anaphylaxis. The basophil activation test provides important advantages in patients with anaphylaxis to beta-lactams, non-steroidal anti-inflammatory drugs, neuromuscular blocking agents and drugs where there is no technique to measure specific IgE.Progress in allergy 01/2010; 95:125-40. -
Article: Toxic epidermal necrolysis related to pemetrexed and carboplatin with vitamin B12 and folic acid supplementation for advanced non-small cell lung cancer.
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ABSTRACT: Pemetrexed is a multitargeted antifolate initially approved as a single agent for the second-line treatment of locally advanced or metastatic non-small cell lung cancer and more recently in the first-line setting combined with cisplatin. The combination of pemetrexed with carboplatin has been tested in several phase II clinical trials showing interesting antitumour activity with mild toxicity. Supplementation with folic acid and vitamin B12 during treatment with pemetrexed is recommended to reduce potential haematological and gastrointestinal adverse events. A patient experienced cutaneous lesions including widespread erythema, epidermal detachment, and skin denudation, associated with deterioration of his general condition after the second cycle of this chemotherapy combination, which was clinically and histologically compatible with toxic epidermal necrolysis (Lyell's syndrome). Treatment with systemic steroids, antihistamines, and antibiotics led to resolution of the skin lesions and improvement of his general condition. To our knowledge, this is the second case reported in the literature of this type of suspected adverse drug reaction associated with a pemetrexed-based chemotherapy combination.Onkologie 10/2009; 32(10):580-4. · 0.87 Impact Factor -
Article: Cellular tests in the diagnosis of drug hypersensitivity.
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ABSTRACT: The application of flowcytometry in the study of basophil activation for the diagnosis of allergic diseases has given interesting results in recent years. The quantification of basophil activation by flowcytometry has been proven to be a useful tool for the assessment of the immediate-type response to allergens mediated by IgE or by other mechanisms in drug allergic patients. Up to now, most basophil activation test studies reported in the literature have used CD69 or CD203c as markers to quantify basophil activation after antigen-specific stimulation. Some technical variations such as the use of whole blood or isolated leukocytes, the addition of IL-3, the conditions of storage of the blood sample, the time of incubation with allergens and their concentration can affect the results of the basophil activation tests. The basophil activation test is more sensitive and specific than other in vitro diagnostic techniques in drug allergy. In various studies, its sensitivity in allergy to muscle relaxant drugs ranges between 36 and 97.7%, with a specificity around 95%. For betalactam antibiotics, basophil activation test sensitivity is 50% and its specificity 90%. For NSAIDs, sensitivity varies between 66% and 75%; specificity is about 93%. Basophil activation test reproduces in vitro hypersensitivity mechanisms involved in immediate-type allergic reactions, allows the diagnosis of allergic and pseudo-allergic reactions particularly for drugs, which are often not detectable by serological techniques, such as determination of specific IgE.Current pharmaceutical design 02/2008; 14(27):2803-8. · 4.41 Impact Factor -
Article: Basophil Activation Test and specific IgE measurements using a panel of recombinant natural rubber latex allergens to determine the latex allergen sensitization profile in children.
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ABSTRACT: There are no documented studies that describe natural rubber latex (NRL) sensitization in children with a history of surgical intervention but without any congenital malformation (urogenital anomalies, spina bifida, etc.), although some authors have studied NRL allergy in children without a history of surgical intervention. The aim of this work was to evaluate the sensitization profile to single NRL allergens in children without spina bifida and without repeated surgical interventions, by using different recombinant and natural latex allergens in two analytical techniques: specific serum immunoglobulin E (IgE) quantification and flow cytometry determination of activated basophils expressing CD63, after stimulating cells from patients with NRL allergens. A total of 23 patients and 10 healthy children were selected. Conjunctival and in-use NRL provocation tests were carried out, as well as specific IgE determination in all patients' and controls' sera with the recombinant NRL allergens: rHev b 1, rHev b 2, rHev b 3, rHev b 5, rHev b 6.01, rHev b 6.02, rHev b 8, rHev b 9 and rHev b 11 and with NRL (k82) using appropriate ImmunoCAPs. The Basophil Activation Test (BAT) was performed with whole latex extract and with the recombinant allergens rHev b 5 and rHev b 6.01, as well as with the natural allergen Hev b 6.02. The sensitivity and the specificity of NRL-specific IgE (k82) were 100%. Positive IgE responses to rHev b 5 were found in sera of 10 children, to rHev b 6.01 in 16 and for rHev b 6.02 in 15 children's sera. Specific IgE to rHev b 8 was found in four sera of the children. We only found significant differences in sensitization to rHev b 5 in children with two or more surgical interventions compared with the non-intervened group or those with only one intervention. Specific IgE in sera of children with latex-fruit syndrome recognized rHev b 6.02, but not to rHev b 11. The patients sensitized to Hev b 8, Hev b 9 and/or Hev b 11 were atopic. The four patients presenting a positive response to the NRL profilin Hev b 8 were allergic to pollen. The BAT against whole NRL extract was positive in 22 of 23 children; against rHev b 5 in 14 of the patients studied; against rHev b 6.01 in seven cases and against nHev b 6.02 in 19 children. In all the control subjects, the results using this technique were negative. If combined rHev b 5, rHev b 6.01 and nHev b 6.02 together, BAT could detect 20 of the 23 children with latex allergy. The combined use of ImmunoCAP with all the recombinant NRL allergens and BAT with rHev b 5, rHev b 6.01 and nHev b 6.02, enabled the identification of NRL allergy in 22 of 23 patients. There is a positive and significant correlation between sensitization to Hev b 5 and the number of interventions. BAT and allergen-specific IgE determination could be used as first-line in vitro diagnostic tests in patients with NRL allergy.Pediatric Allergy and Immunology 04/2006; 17(2):148-56. · 2.46 Impact Factor -
Article: Drug hypersensitivities: which room for biological tests?
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ABSTRACT: Drug allergic reactions frequently represent a serious diagnostic problem. In this paper we summarise the most relevant data published in recent years on the diagnostic reliability of the in vitro techniques in drug allergy diagnosis. The lymphocyte transformation test (LTT) offers a sensitivity of 58% in the diagnosis of late allergic reactions to betalactams and 64.5% in the immediate allergic reactions. The basophil activation test and the antigen-specific sulphidoleukotriene determination have an acceptable diagnostic reliability in muscle relaxant drug-induced reactions and in betalactam allergy. BAT sensitivity in betalactam allergy was 50.7% and its specificity 93.3%, whereas CAP had a sensitivity of 36.7% and a specificity of 83.3%, and CAST, a sensitivity of 47.7% and a specificity of 83.3%. For NSAID hypersensitivity, BAT sensitivity was 63.3% and specificity 93.3%, CAST sensitivity was 38.3% and specificity 76.6%. BAT sensitivity in metamizol allergy was 42.3% and the specificity 100% and CAP was negative in all the 17 cases in which it was performed. The joint use of BAT and CAP (specific IgE) allows diagnosis of 65.2% of the betalactam allergic patients with a specificity of 83.3%. The combined use of CAST and BAT in metamizol allergy detects 76% of the cases and 76.9% when associating the skin tests. In NSAID hypersensitivity, the joint use of BAT and CAST does not increase the diagnostic reliability of BAT alone. BAT is a non-invasive useful technique in the in vitro diagnosis of betalactam and metamizol allergy, and NSAID hypersensitivity.European annals of allergy and clinical immunology 07/2005; 37(6):230-5. -
Article: Recombinant Pru p 3 and natural Pru p 3, a major peach allergen, show equivalent immunologic reactivity: a new tool for the diagnosis of fruit allergy.
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ABSTRACT: The peach lipid transfer protein Pru p 3 has been identified as a major allergen from this fruit. Homologous cross-reactive allergens have been found in several plant foods and pollens. Recombinant Pru p 3 has been recently produced in the yeast Pichia pastoris. We sought to evaluate the potential role of recombinant Pru p 3 as a novel tool for the diagnosis of fruit allergy. Circular dichroism analysis was used to compare the protein folding of natural Pru p 3 and recombinant Pru p 3. IgE binding by both molecular forms was quantified by means of ELISA and ELISA inhibition assays, and their biologic activity was estimated by using basophil activation, histamine release, and sulphidoleukotriene production tests. Individual sera or blood samples from patients with peach allergy (up to 17) were used in the assays. A nearly identical circular dichroism spectra was shown by using natural Pru p 3 and recombinant Pru p 3, indicating that both protein forms are similarly folded. No difference was detected in the IgE-binding capacity of the 2 mo-lecular versions. Basophil activation and induction of sulphidoleukotriene production were positive in 9 of 10 patients, and histamine release was induced in at least half of the patients, with similar effects of the natural and recombinant forms in the 3 assays. Recombinant Pru p 3 shows a strong immunologic activity equivalent to that of its natural counterpart, and therefore it can be a useful tool for diagnosis (and future immunotherapy) of fruit allergy.Journal of Allergy and Clinical Immunology 04/2003; 111(3):628-33. · 11.00 Impact Factor -
Article: Flow-cytometric cellular allergen stimulation test in latex allergy.
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ABSTRACT: The use of flow-cytometric basophil activation to different allergens has been recommended in recent years. In this study, we analyzed the diagnostic reliability of the flow-cytometric allergen stimulation test (FAST) after latex-specific stimulation in vitro. The diagnostic reliability of the technique was assessed as well as its correlation with other in vitro diagnostic parameters. 43 patients allergic to latex with a positive history and skin test participated in the study. Thirty subjects (20 of them exposed to latex) with a negative history, skin tests and serum-specific IgE determination to latex were used as controls. In FAST the percentage of basophils that express CD63 as an activation marker after in vitro stimulation with allergen (latex) is determined by flow cytometry, following double labelling with the monoclonal antibodies anti-CD63-PE and anti-IgE FITC. Intraclass correlation coefficient in FAST with latex was 0.995 (p < 0.0001), which demonstrates the excellent reproducibility of this technique. Taking a cutoff point of 10% by means of ROC curves, FAST yields a sensitivity of 93% and a specificity of 100%. The FAST positive predictive value in latex allergy was 100% and the negative predictive value was 99.9%. We found a positive and significant correlation between FAST and specific IgE (CAP) with the histamine release test and specific sulphidoleukotriene production [cellular allergen stimulation test (CAST); p < 0.05]. FAST is a highly reliable technique (93% sensitivity and 100% specificity) in the in vitro diagnosis of IgE-mediated latex allergy.International Archives of Allergy and Immunology 02/2003; 130(1):33-9. · 2.40 Impact Factor -
Article: Flow cytometric basophil activation test: a review.
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ABSTRACT: Flow cytometry is a technique enabling the analysis of physical and biological characteristics of cells or other biological particles when labeled with antibodies coupled to fluorochromes or other dyes. The basophil activation test (BAT), also called flow-cytometric allergen stimulation test (FAST) [commercially available under the name of Flow CAST (Bühlmann Laboratories) or BASOTEST (Beckton-Dickinson)] is based on the in vitro allergen-induced specific activation of basophils. This assay rests on the demonstration of some membrane protein markers that appear after exposure to the allergen. This paper reviews some of the literature about the use of this technique in the investigation of immediate-type allergies to inhalant allergens, drugs, and foods, as well as our own experience with this diagnostic technique. Flow cytometry is a reliable method for the quantification of basophil activation after allergenic stimulus in vitro and in vivo. It also enables us to detect allergic and pseudoallergic reactions because of other mechanisms than allergen-specific IgE antibodies. Further clinical evaluation of this technique will allow validation and better establishment of its diagnostic value in allergy.Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 02/2002; 12(3):143-54. · 2.27 Impact Factor
Top co-authors
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Institutions
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2011
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Hospital de Basurto
Bilbao, Basque Country, Spain
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2010
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Clínica Universidad de Navarra
Madrid, Madrid, Spain
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2002–2008
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Universidad de Navarra
- Department of Allergology and Clinical Immunology
Pamplona, Navarre, Spain
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