M Blanca

University of Lorraine, Nancy, Lorraine, France

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Publications (410)2525.18 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Allergen immunotherapy (AIT), the etiologic treatment of allergic rhinoconjunctivitis and allergic asthma, has been shown to be an effective and safe treatment in patients with allergic respiratory disease. The efficacy of AIT in reducing symptoms and medication requirements has been demonstrated not only during treatment but also after it is discontinued. AIT is the only treatment that has the ability to modify the natural course of allergic rhinoconjunctivitis and asthma. In recent years, a new entity—local allergic rhinitis (LAR)—has been reported, which is characterized by the presence of a local allergic response to inhalant allergens, with negative skin tests and no detection of specific IgE antibodies in the peripheral blood. Patients had a nasal-specific response after nasal allergen challenge and a nasal Th2 inflammatory response with specific IgE antibodies, and showed clinical improvement with the classical treatment for allergic rhinitis (antihistamines and nasal corticosteroids). Ongoing evidence indicates that these patients benefit from subcutaneous AIT and supports this indication for LAR. Key points 1. LAR is a new phenotype of allergic rhinitis characterized by the presence of a localized allergic response in the nasal mucosa with negative skin test and no detection of serum-specific IgE antibodies in the peripheral blood. 2. It is an underdiagnosed/misdiagnosed respiratory disease that may affect patients from different countries and among different ethnic and age groups, showing a tendency toward worsening of the disease and a risk of developing asthma. 3. Patients with LAR commonly have persistent rhinitis, with moderate to severe nasal symptoms associated with conjunctivitis and/or asthma and impairment of their quality of life. 4. AIT is the etiological treatment of allergic respiratory disease and has the ability to modify its natural course. According to ARIA guidelines, it is indicated in moderate to severe persistent or intermittent allergic rhinitis and/or allergic asthma. 5. The efficacy and safety of subcutaneous allergen-specific immunotherapy for grass pollen and Dermatophagoides pteronyssinus has been demonstrated in adults with LAR.
    Current Treatment Options in Allergy. 01/2015;
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    ABSTRACT: We introduce the reader to systems biology, using adverse drug reactions (ADRs), specifically hypersensitivity reactions to multiple non-steroidal anti-inflammatory drugs (NSAIDs), as a model. To disentangle the different processes that contribute to these reactions - from drug intake to the appearance of symptoms - it will be necessary to create high-throughput datasets. Just as crucial will be the use of systems biology to integrate and make sense of them. We review previous work using systems biology to study related pathologies such as asthma/allergy, and NSAID metabolism. We show examples of their application to NSAIDs-hypersensitivity using current datasets. We describe breakthroughs in high-throughput technology and speculate on their use to improve our understanding of this and other drug-induced pathologies. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Trends in Pharmacological Sciences 01/2015; · 9.99 Impact Factor
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    ABSTRACT: Local allergic rhinitis (LAR) is characterized by the presence of a nasal Th2 inflammatory response with local production of specific IgE antibodies and a positive response to a nasal allergen provocation test (NAPT) without evidence of systemic atopy.The prevalence has been shown to be up to 25% in subjects affected with rhinitis with persistence, comorbidity and evolution similar to allergic rhinitis. LAR is a consistent entity that does not evolve to allergic rhinitis with systemic atopy over time although patients have significant impairment in quality of life and increase in the severity of nasal symptoms over time. Lower airways can be also involved.The diagnosis of LAR is based mostly on demonstration of positive response to NAPT and/or local synthesis of specific IgE. Allergens involved include seasonal or perennial such as house dusts mites, pollens, animal epithelia, molds (alternaria) and others. Basophils from peripheral blood may be activated by the involved allergens suggesting the spill over of locally synthesized specific IgE to the circulation. LAR patients will benefit from the same treatment as allergic patients by using antihistamines, inhaled corticosteroids and IgE antagonists. Studies on immunotherapy are ongoing and will determine its efficacy in LAR in terms of symptoms improvement and evolution of the natural course of the disease.This article is protected by copyright. All rights reserved.
    Clinical & Experimental Allergy 12/2014; · 4.32 Impact Factor
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    ABSTRACT: Non-immediate drug reactions (NIR) are induced by specific immunological mechanisms and involve the recognition of hapten molecules by the immune system, with the participation of dendritic cells and other antigen-presenting cells. This process is followed by an effector response that can induce several clinical entities, ranging from mild to severe. The type of immunological recognition can be used as the basis for the diagnostic approach. Both in vivo and in vitro tests are available for the diagnosis of NIR. In vivo tests consist of the reproduction of a diminished immune response with the culprit drug and in vitro tests are based on the stimulation of memory cells in culture. If both tests give negative results, a drug provocation test can be used.
    Expert Review of Clinical Immunology 10/2014; · 3.34 Impact Factor
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    ABSTRACT: Metamizole is a pain-killer drug that has been banned in some countries because of its toxicity, but it is still used in many countries due to its effective analgesic and antispasmodic properties. Although large variability in the biodisposition and adverse effects of metamizole are known, factors underlying this variability are poorly understood. We analyzed the urinary recovery of metabolites, as well as the association of these profiles with genetic and non-genetic factors, in a group of 362 healthy individuals. Gender and functional polymorphisms are strongly related to metabolic profiles. N-demethylation of the active metabolite MAA is diminished in carriers of the CYP2C19*2 allele and in NAT2-slow acetylators. Acetylation of the secondary metabolite AA is decreased in men, in drinkers and in NAT2-slow acetylators with a differential effect of NAT2*5 and NAT2*6 alleles. The formylation of MAA is diminished in older subjects and in carriers of defect CYP2C9 and CYP2C19 alleles. Two novel arachidonoyl metabolites were identified for the first time in humans. Women and NAT2-slow acetylators show higher concentrations, whereas the presence of the rapid CYP2C19*17 allele is associated with lower concentrations of these metabolites. All genetic associations show a gene-dose effect. We identified for the first time genetic and non-genetic factors related to the oxidative metabolism of analgesic drug metamizole, as well as new active metabolites in humans. The phenotypic and genetic factors identified in this study have a potential application as biomarkers of metamizole biotransformation and toxicity.
    Biochemical Pharmacology 09/2014; 91(5). · 4.65 Impact Factor
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    ABSTRACT: Immediate reactions to β-lactams are the most common causes of anaphylactic reactions and can be life-threatening. The few known genetic factors influencing these reactions suggest a link with atopy and inflammation.
    Journal of Allergy and Clinical Immunology 09/2014; · 11.25 Impact Factor
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    ABSTRACT: Apple allergy manifests as two main groups of clinical entities reflecting different patterns of allergen sensitization: oral allergy syndrome (OAS) and generalized symptoms (GS).
    PLoS ONE 09/2014; 9(9):e107304. · 3.53 Impact Factor
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    ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs most commonly involved in hypersensitivity drug reactions. Such reactions can be due to the release of inflammatory mediators in the absence of specific immunologic recognition, or immunoglobulin E (IgE)- or T-cell-selective responses. The former include upper and lower airway symptoms in patients with chronic underlying respiratory disease, the exacerbation of chronic spontaneous urticaria, and the induction of cutaneous symptoms. The latter include selective responses to a single NSAID with good tolerance to strong cyclooxygenase-1 inhibitors, with a putative IgE or T-cell mechanism proposed. These reactions can be acute or delayed.
    Immunology and Allergy Clinics of North America 08/2014; 34(3):507–524. · 2.22 Impact Factor
  • Bernard Y Thong, Miguel Blanca
    Current Opinion in Allergy and Clinical Immunology 08/2014; 14(4):269-270. · 3.40 Impact Factor
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    ABSTRACT: The human leukocyte antigen (HLA) genes have a fundamental role in immunity. Polymorphisms at HLA-DRB1 and HLA-DQB1 are well known to impact asthma susceptibility as indicated by many candidate-gene and genome-wide association studies (GWAS). We sought to better understand the associations at these two loci performing an association study of SNPs and imputed classic alleles from HLA-DRB1 and HLA-DQB1 genes with asthma using a two-stage case-control study. We first selected 22 SNPs that allow to accurately defining classic alleles at these HLA genes in European populations, and evaluated their ability to predict classic alleles in individuals from the Spanish population with paired data for classic alleles. Then, we tested the association of accurately predicted classic alleles in a total of 3,115 samples from Spain. We identified 2 SNPs, constituting eQTLs in the region, and one classic allele (HLA-DRB1*15:01) that were consistently associated with asthma across the two stages. Interestingly, the 2 SNPs showed concordant allelic effects in asthma with the ones shown with lipid traits. In addition, a third SNP demonstrated a strong association effect with allergen-specific sensitization among asthma cases. Besides, we describe for the first time a classic allele-based pleiotropic effect for HLA-DRB1*15:01, being opposite between asthma and other immune-related diseases. These results lines up with previous evidence showing some other genes firmly involved in asthma pathogenesis that also demonstrate opposite effects in autoimmune diseases.
    The Journal of allergy and clinical immunology 07/2014; · 12.05 Impact Factor
  • International Archives of Allergy and Immunology 07/2014; 164(2):147-148. · 2.25 Impact Factor
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    ABSTRACT: Hypersensitivity drug reactions (HDRs) encompass a wide spectrum of unpredictable clinical entities. They represent an important health problem, affecting people of all ages, and lead to a large strain on the public health system. Here, we summarise experiments that use high throughput genomics technologies to investigate HDRs. We also introduce the field of systems biology as a relatively recent discipline concerned with the integration and analysis of high throughput datasets such as DNA microarrays and next generation sequencing data. We describe previous studies that have applied systems biology techniques to related fields such as allergy and asthma. Finally, we present a number of potential applications of systems biology to the study of HDRs, in order to make the reader aware of the types of analyses that can be performed and the insights that can be gained through their application.This article is protected by copyright. All rights reserved.
    Clinical & Experimental Allergy 07/2014; · 4.32 Impact Factor
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    ABSTRACT: Background Drugs are responsible for 40% to 60% of anaphylactic reactions treated in the emergency department. A global research agenda to address uncertainties in anaphylaxis includes studies that identify factors associated with morbidity and mortality. Objective The present study investigated drug-induced anaphylaxis, etiologies, aggravating factors, and treatment. Methods A total of 806 patients with adverse drug reactions were screened, and those who had a clinical diagnosis of anaphylaxis were included in the study. Clinical and demographic characteristics of anaphylaxis were described, including etiologies, pathophysiologic mechanisms involved in the reactions, and a personal history of atopy and asthma. Factors associated with disease severity also were identified. Results Anaphylaxis was diagnosed in 117 patients (14.5%). The etiologies were defined in 76% of the cases, nonsteroidal anti-inflammatory drugs being the most frequent. Seventy-eight patients (66.7%) reported a previous reaction to the drug involved in the current reaction or to a drug from the same class and/or group. Epinephrine was used to treat 34.2% of patients who presented with anaphylaxis, and 40.8% of those with anaphylactic reactions with cardiovascular involvement. IgE-mediated reactions were associated with greater severity, manifested by the rates of cardiovascular dysfunction, hospitalization, and use of epinephrine. Conclusions The prevalence of anaphylaxis is high in patients who seek medical assistance for drug reactions, but its diagnosis is missed in emergency services, and adrenaline is underused. Drugs were prescribed to many patients despite a history of previous reaction. Nonsteroidal anti-inflammatory drugs were implicated in most cases of anaphylaxis induced by drugs, and IgE-mediated reactions were less frequent but more severe.
    The Journal of Allergy and Clinical Immunology: In Practice. 07/2014;
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    ABSTRACT: Background Act d 12 (11S globulin) and Act d 13 (2S albumin) are two novel relevant allergens from kiwi seeds that might be useful to improve the diagnostic sensitivity and the management of kiwifruit allergic patients.Objective: To perform a comprehensive structural and immunological characterization of purified Act d 12 and Act d 13 from kiwi seeds.Methods Sera from 55 well-defined kiwifruit allergic patients were used. Act d 12 and Act d 13 were purified by chromatographic procedures. Circular dichroism, mass spectrometry, concanavalinA detection, immunoblotting, enzyme-linked immunosorbent assays, basophil activation tests and IgE-inhibition experiments were used.ResultsAct d 12 and Act d 13 were purified from kiwi seeds to homogeneity by combining size-exclusion, ion-exchange and RP-HPLC chromatographies. Both purified allergens preserve the structural integrity and display typical features of their homologous counterparts from the 11S globulin and 2S albumin protein families, respectively. These allergens are released from kiwi seeds after oral and gastric digestion of whole kiwifruit, demonstrating their bioavailability after ingestion. The allergens retain the capacity to bind serum IgE from kiwifruit allergic patients, induce IgE cross-linking in effector circulating basophils and display in vitro IgE cross-reactivity with homologous counterparts from peanut and tree nuts.Conclusion Purified Act d 12 and Act d 13 from kiwi seeds are well-defined molecules involved in in vitro IgE cross-reactivity with peanut and tree nuts. Their inclusion in component-resolved diagnosis of kiwifruit allergy might well contribute to improve the diagnostic sensitivity and the management of kiwifruit allergic patients.This article is protected by copyright. All rights reserved.
    Allergy 07/2014; · 6.00 Impact Factor
  • Journal of Allergy and Clinical Immunology 06/2014; · 11.25 Impact Factor
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    ABSTRACT: Ara h 1, Ara h 2, and Ara h 3 are important sensitizers in peanut allergy. Ara h 9 has also been shown to be relevant in the Mediterranean area. We evaluated the basophil response to peanut allergens and Pru p 3 in Mediterranean patients: Group 1, peanut and peach allergy; Group 2, peanut allergy and tolerance to peach; Group 3, peach allergy and tolerance to peanut; Group 4, nonallergic subjects that tolerate both peanut and peach. Compared to controls (Group 4), there was an increased basophil activation with Ara h 2 (P = 0.031) and Pru p 3 (P = 0.009) in Group 1 and with Ara h 1 (P = 0.016), Ara h 2 (P = 0.001), and Ara h 9 (P = 0.016) in Group 2. Importantly, only Ara h 2 showed an increased activation (P = 0.009) in Group 2 compared to Group 3. Ara h 2 is the best discriminating allergen for peanut allergy diagnosis in a Mediterranean population showing two patterns: patients also allergic to peach, responding to Ara h 2 and Pru p 3, and patients allergic only to peanut, responding to Ara h 1, Ara h 2, and Ara h 9.
    Allergy 05/2014; · 6.00 Impact Factor
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    The Journal of allergy and clinical immunology 04/2014; · 12.05 Impact Factor
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    ABSTRACT: Background Asthma is characterized by airway inflammation and remodelling in which matrix metalloproteinases (MMPs) play an important role. MMP-9 is the major MMP found in the bronchoalveolar lavage fluids and bronchial biopsies from patients with allergic asthma after allergen challenge, where it correlates with the count of neutrophils and macrophages. However, the cellular sources of MMP-9 in this inflammatory condition have not yet been clearly identified. This work was undertaken to analyse whether neutrophils may be a source of MMP-9 in the allergic asthma condition upon allergen challenge.Methods Neutrophils from allergic asthmatic patients were in vitro stimulated, and the levels of MMP-9 release were measured in the cell culture supernatants using enzyme-linked immunosorbent assay (ELISA) and zymography.ResultsWe show that MMP-9 is released by neutrophils, but not by eosinophils from allergic asthmatic patients in response to allergens to which the patients were sensitized. Neutrophils also released MMP-9 in response to anti-IgE Abs, and agonist Abs against FcεRI, FcεRII/CD23 and galectin-3. Inhibitors of transcription and translation, actinomycin D and cycloheximide, partially cancelled this process, suggesting that MMP-9 is also de novo synthesized in response to stimuli. We also show evidence that the MAPKs, p38 and extracellular signal-regulated kinase, as well as the transcription factor NF-κB, are involved, as specific chemical inhibitors of these cell-signalling pathways abolished the anti-IgE/allergen-dependent MMP-9 release.Conclusions These data demonstrate that the exposure of neutrophils to allergens leads to generation of MMP-9, which may then lead to remodelling in asthma.
    Allergy 04/2014; · 6.00 Impact Factor
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    ABSTRACT: Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13×10-6), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs.
    PLoS ONE 03/2014; 9(3):e90966. · 3.53 Impact Factor
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    ABSTRACT: Allergic reactions towards β-lactam antibiotics pose an important clinical problem. The ability of small molecules, such as a β-lactams, to bind covalently to proteins, in a process known as haptenation, is considered necessary for induction of a specific immunological response. Identification of the proteins modified by β-lactams and elucidation of the relevance of this process in allergic reactions requires sensitive tools. Here we describe the preparation and characterization of a biotinylated amoxicillin analog (AX-B) as a tool for the study of protein haptenation by amoxicillin (AX). AX-B, obtained by the inclusion of a biotin moiety at the lateral chain of AX, showed a chemical reactivity identical to AX. Covalent modification of proteins by AX-B was reduced by excess AX and vice versa, suggesting competition for binding to the same targets. From an immunological point of view, AX and AX-B behaved similarly in RAST inhibition studies with sera of patients with non-selective allergy towards β-lactams, whereas, as expected, competition by AX-B was poorer with sera of AX-selective patients, which recognize AX lateral chain. Use of AX-B followed by biotin detection allowed the observation of human serum albumin (HSA) modification by concentrations 100-fold lower that when using AX followed by immunological detection. Incubation of human serum with AX-B led to the haptenation of all of the previously identified major AX targets. In addition, some new targets could be detected. Interestingly, AX-B allowed the detection of intracellular protein adducts, which showed a cell type-specific pattern. This opens the possibility of following the formation and fate of AX-B adducts in cells. Thus, AX-B may constitute a valuable tool for the identification of AX targets with high sensitivity as well as for the elucidation of the mechanisms involved in allergy towards β-lactams.
    PLoS ONE 03/2014; 9(3):e90891. · 3.53 Impact Factor

Publication Stats

5k Citations
2,525.18 Total Impact Points


  • 2013–2014
    • University of Lorraine
      • Faculty of medicine
      Nancy, Lorraine, France
  • 2012–2014
    • Civil Hospital, Raikot
      Rāikot, Punjab, India
    • Hospital Universitari Mutua de Terrassa
      Terrassa, Catalonia, Spain
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1988–2014
    • Hospital Regional Universitario de Málaga
      • • Departamento de Medicina Interna
      • • Departamento de Alergología
      Málaga, Andalusia, Spain
  • 2011–2013
    • Universidad de Extremadura
      • • Departamento de Fisiología
      • • Departamento de Bioquímica, Biología Molecular y Genética
      Ara Pacis Augustalis, Extremadura, Spain
    • Tan Tock Seng Hospital
      Tumasik, Singapore
  • 2009–2013
    • Hospital Universitario Infanta Leonor
      Madrid, Madrid, Spain
    • Hospital 12 de Octubre
      Madrid, Madrid, Spain
  • 2002–2011
    • University of Malaga
      • Department of Organic Chemistry
      Málaga, Andalusia, Spain
  • 2001–2011
    • Complesso Integrato Columbus
      Roma, Latium, Italy
  • 2000–2011
    • Hospital Universitario La Paz
      • Servicio de Alergología
      Madrid, Madrid, Spain
  • 2006
    • Hospital Virgen del Camino
      Cádiz, Andalusia, Spain
  • 2003
    • Karl-Franzens-Universität Graz
      Gratz, Styria, Austria
  • 1999
    • Hospital General Universitario de Elche
      Elche, Valencia, Spain
    • University of Milan
      Milano, Lombardy, Italy
  • 1998–1999
    • Catholic University of the Sacred Heart
      • Institute of Internal and Geriatric Medicine
      Milano, Lombardy, Italy
  • 1997
    • Hospital Universitario San Cecilio
      Granata, Andalusia, Spain