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ABSTRACT: In the present study, we investigated the immunomodulatory activity of multi-walled carbon nanotubes (MWCNT) in peripheral blood mononuclear cells (PBMC) from healthy donors and mite-allergic subjects. Freshly prepared PBMCs, stimulated or not with Toll-like receptor (TLR)1 to 9 agonists, a T cell mitogen (phytohemagglutinin A) or mite allergen extract were cultured in the presence or absence of MWCNTs. Secretion of TNF-α, IL-2, IL-5, IL-6, IL-12/23p40 or IFN-γ was quantified in the culture supernatants by ELISA. Basal secretion of all the cytokines was not altered by MWCNTs in PBMCs from both healthy donors and allergic subjects. In PBMCs from healthy donors, TNF-α, IL-6 and IL-12/23p40 secretion in response to the TLR4 agonist, lipopolysaccharide was however increased in a dose-dependent manner by MWCNTs. Significant increases in the release of these cytokines were also observed in PBMCs stimulated with a TLR2 or TLR3 agonist. MWCNTs also increased the release of IL-2 and IFN-γ by PBMCs stimulated with a T cell mitogen. In contrast, MWCNTs inhibited allergen-induced IL-5 secretion by PBMCs from mite-allergic subjects. As well, MWCNTs altered the capacity of PBMC-derived monocytes to differentiate into functional dendritic cells. All together, our data suggest that according to its immune cell target, MWCNTs may either promote or suppress immune responses in humans. Further investigations are necessary to fully understand the complexity behind interactions of engineered nanoparticles with the immune system.
Toxicology Letters 12/2012; · 3.23 Impact Factor
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Anne Casset,
Adriano Mari,
Ashok Purohit,
Yvonne Resch,
Margit Weghofer,
Rosetta Ferrara,
Wayne R Thomas,
Claudia Alessandri,
Kuan-Wei Chen, Frédéric de Blay,
Rudolf Valenta,
Susanne Vrtala
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ABSTRACT: Background: Diagnosis and immunotherapy of house-dust mite (HDM) allergy is still based on natural allergen extracts. The aim of this study was to analyze commercially available Dermatophagoides pteronyssinus extracts from different manufacturers regarding allergen composition and content and whether variations may affect their allergenic activity. Methods: Antibodies specific for several D. pteronyssinus allergens (Der p 1, 2, 5, 7, 10 and 21) were used to analyze extracts from 10 different manufacturers by immunoblotting. Sandwich ELISAs were used to quantify Der p 1 and Der p 2 in the extracts. Mite-allergic patients (n = 45) were skin-tested with the extracts and tested for immunoglobulin E (IgE) reactivity to a panel of 10 mite allergens (Der p 1, 2, 4, 5, 7, 8, 10, 14, 20 and 21) by dot blot. Results: Only Der p 1 and Der p 2 were detected in all extracts but their concentrations and ratios showed high variability (Der p 1: 6.0-40.8 µg ml(-1); Der p 2: 1.7-45.0 µg ml(-1)). At least 1 out of 4 allergens (i.e. Der p 5, 7, 10 and 21) was not detected in 8 of the studied extracts. Mite-allergic subjects showed different IgE reactivity profiles to the individual mite allergens, the extracts showed different allergenic activity in skin-prick tests and false-negative results. Conclusions: Commercially available D. pteronyssinus extracts lack important allergens, show great variability regarding allergen composition and content and some gave false-negative diagnostic test results in certain patients.
International Archives of Allergy and Immunology 06/2012; 159(3):253-62. · 2.40 Impact Factor
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Soins. Chirurgie 11/2011;
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Denis Charpin,
Ralph Baden,
Valérie Bex,
Sandrine Bladt,
Carmel Charpin-Kadouch,
Catherine Keimeul,
Pedro da Mata, Frédéric de Blay,
Martyna Kuske,
Yvon Le Moullec,
Alain Nicolas,
Martine Ott,
Roger Marc,
Chrisbelle Speyer,
Daniel Vervloet,
Fabien Squinazi
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ABSTRACT: This review deals with environmental home inspection services in Western Europe provided for patients at the request of attending physicians to improve patient management. Such requests are usually motivated by respiratory or general symptoms which occur or worsen at home. The visit includes a standardised questionnaire as well as environmental sampling such as mite-allergen measurement, mould identification and volatile organic compound (VOC) measurements. Besides, some non-respiratory indoor risks are also taken into account. Following the visit, a report is sent to the family and the attending physician. These services have been developed since the early 1990s, but evaluation of their efficacy is still limited. Some studies have demonstrated a reduction in mite-allergen levels and clinical improvement following the visit and implementation of advice provided to the family. However, more studies are needed to further document efficacy and also perform cost-benefit analysis of these services.
Environmental Health and Preventive Medicine 03/2011; 16(2):73-9.
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Dermatology 10/2009; 220(1):51-2. · 2.05 Impact Factor
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The Journal of allergy and clinical immunology 08/2008; 122(1):217-8. · 9.17 Impact Factor
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Journal of Allergy and Clinical Immunology 07/2008; 122(1):217-218. · 11.00 Impact Factor
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The Journal of allergy and clinical immunology 02/2008; 121(1):253-4. · 9.17 Impact Factor
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ABSTRACT: Sublingual immunotherapy (SLIT) is accepted as a safe and effective route for the treatment of grass pollen allergy, but clarification of its clinical and biological efficacy requires more study.
To evaluate the efficacy, safety, and compliance of SLIT with a standardized 3-grass pollen extract in patients with grass pollen seasonal allergic rhinoconjunctivitis, with or without mild asthma.
This multicenter, randomized, double-blind study included 127 patients (aged 12-41 years; mean age, 24.9 years) with grass pollen seasonal allergic rhinoconjunctivitis, with or without mild asthma. They received either SLIT with a high-dose, standardized, 3-grass pollen extract or placebo for 10 months before and during the grass pollen season. The efficacy evaluation compared weekly clinical scores (defined as the sum of the symptom score and rescue medication score) to measure rhinoconjunctivitis and asthma for the first 8 weeks of the pollen season. We also evaluated safety and compliance and measured changes in anti-Dactylis specific IgG4 antibody levels.
There was a trend in favor of the study group in the mean adjusted clinical score. The groups were not comparable on inclusion (P = .02): the SLIT group included more subjects with asthma and had a higher mean IgG4 serum level. Additional exploration according to subgroups with and without asthma found that among the patients without asthma, the SLIT group had a significantly better clinical score (P = .045). Anti-Dactylis specific IgG4 levels increased significantly in the SLIT group.
SLIT with a standardized, high-dose, 3-grass pollen extract is safe and significantly improves the clinical score in patients with hay fever and without asthma during the pollen season.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 12/2007; 99(5):453-61. · 2.83 Impact Factor
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ABSTRACT: A recombinant hybrid molecule (HM) consisting of 4 major allergens from timothy grass (Phl p 1, 2, 5, and 6) was expressed in Escherichia coli, purified, and characterized regarding its immunologic properties.
We sought to determine whether the recombinant HM can be used for the diagnosis of grass pollen allergy by means of skin testing.
Skin prick testing was performed in 32 patients with grass pollen allergy and in 9 control individuals by using increasing concentrations (4, 12, 36, and 108 mug/mL) of the HM and using commercial grass pollen extract. Specific IgE reactivities against the HM, grass pollen extract, and a panel of purified grass pollen allergens (recombinant Phl p 1, 2, 5, 6, 7, 12, and 13 and natural Phl p 4) were measured by means of ELISA, and timothy grass pollen-specific IgE levels were determined by using ImmunoCAP.
Grass pollen allergy was diagnosed in all patients by means of skin testing with the HM. No false-positive skin test responses were obtained in the control individuals. There was an excellent correlation between IgE levels obtained with the HM and natural grass pollen extract measured by means of ELISA (r = 0.98, P < .0001) and by means of ImmunoCAP (r = 0.98, P < .0001).
The recombinant HM permitted accurate and specific in vivo diagnosis of grass pollen allergy in all tested patients. It can be considered a well-defined tool for the diagnosis and perhaps for immunotherapy of grass pollen allergy.
A recombinant HM can replace traditional allergen extracts for skin test-based diagnosis of grass pollen allergy.
Journal of Allergy and Clinical Immunology 08/2007; 120(2):315-21. · 11.00 Impact Factor
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ABSTRACT: Although major house dust mite allergen (Der p 1) is carried mainly on large particles (>10 microm), standard bronchial challenge tests (BCT) use nebulizers that deliver smaller particles (sizes from 1 to 5 microm) and may therefore not reflect actual domestic exposure. The objective of this study was to evaluate the influence of particle size of Dermatophagoides pteronyssinus extract on bronchial response. Specific BCT were performed with different mass median aerodynamic diameters (MMAD): 1.1, 5.6, and 9.7 microm. Each of the 19 mite-sensitized patients underwent mite BCT three times, once with each nebulizer. IL-5 levels were assessed in induced sputum and blood samples. The PD(20) for Der p 1 differed substantially with particle size, with less Der p 1 (11.2 ng) needed to produce a PD(20) with the largest particles (9.7 microm), compared to 18.1 ng for the 5.6 microm particles and 142.5 ng for the 1.1 microm particles (p < 0.0001). Large particles also induced an early phase response significantly more often than small particles (100% vs. 63%). Although the late phase reaction (LPR) frequency was similar with all three particle sizes, lower mean oral corticosteroid doses were needed to treat LPR with the largest particles (23 mg), compared to the smaller particles, with 34 mg for the 5.6 microm particles and 51 mg for the 1.1 microm. The 1.1 microm particles produced a significantly greater increase in IL-5 concentrations in sputum and blood compared to the larger particles. Large particles clearly play a role in the immediate bronchial response in asthmatics sensitized to mites and, therefore, should be included in pharmacological studies in humans.
Journal of Aerosol Medicine 02/2007; 20(4):509-18. · 1.61 Impact Factor
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ABSTRACT: We have shown previously that lipopolysaccharides (LPS) inhibited airway inflammation in allergen-sensitized and challenged mice when administered during sensitization, while exacerbating the inflammation when given upon challenge. We have here investigated the effect of LPS administered during both sensitization and challenge on airway inflammation, as well as on the profile of the T-helper (Th) response to allergen.
Mice were sensitized and challenged with ovalbumin (OVA), in the presence or absence of effective doses of LPS, namely 1 mug during sensitization and 1 ng during challenge. Inflammation was assessed by measuring cell counts and cytokine levels in bronchoalveolar lavage fluid (BALF). The profile of the Th response was determined by quantifying OVA-specific IgE and IgG2a in serum and Th1/Th2 cytokines in the culture medium of splenocytes and in BALF.
Allergen-induced airway eosinophilia was increased in mice exposed to LPS during challenge only when compared with controls, whereas it was similarly reduced in animals exposed during sensitization only and during both sensitization and challenge. Mice exposed to LPS during sensitization only or during both sensitization and challenge also displayed a decrease in IgE and an increase in IgG2a, suggesting a switch in the immune response toward the Th1 profile. This was confirmed by quantification of Th1/Th2 cytokines in culture medium of splenocytes and in BALF.
Our data demonstrate that exposure to endotoxins during sensitization prevents allergen-induced airway inflammation, as well as its exacerbation triggered by further exposure to endotoxins during challenge, while switching the immune response to allergen from a Th2 to a Th1 profile.
International Archives of Allergy and Immunology 01/2006; 138(4):298-304. · 2.40 Impact Factor
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ABSTRACT: Airways repair is critical to lung function following transplantation. We hypothesised that the stem cell factor (SCF) could play a role in this setting.
We studied 9 lung transplant recipients (LTx recipients) during their first year postgraft, and evaluated SCF mRNA expression in bronchial biopsy specimens using on-line fluorescent PCR and SCF protein levels in bronchoalveolar lavage (BAL) and serum using ELISA. The expression of SCF receptor Kit was assessed using immunostaining of paraffin-embedded bronchial sections.
SCF mRNA was highly expressed during the early postgraft period [Month (M)1-M3] (300% increase vs controls: 356 vs 1.2 pg SCF/microg GAPDH cDNA, p < 0.001) and decreased thereafter (M4-M12: 187 pg/microg), although remaining at all times 10-100 times higher than in controls. While SCF protein levels in BAL were similar in LTx recipients and in controls, the SCF serum levels were at all times higher in LTx recipients than in controls (p < 0.05), with no relationship between these levels and the acute complications of the graft. Finally, Kit was strongly expressed by the mast cells as well as by the bronchial epithelium of LTx recipients.
SCF and Kit are expressed in bronchial biopsies from lung transplant recipients irrespective of the clinical status of the graft. A role for these factors in tissue repair following lung transplantation is hypothesised.
Respiratory research 01/2006; 7:90. · 3.36 Impact Factor
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Frédéric de Blay
La Revue du praticien 07/2005; 55(12):1293-4.
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ABSTRACT: Three hypotheses are described to explain the relation between allergens and environmental co-factors and the onset of atopy: the hygiene hypothesis, the allergenic hypothesis, and the high exposure tolerance inducing a Th2 derived response with blocking IgG4 synthesis. None of these hypotheses have been confirmed. It seems thus difficult to give recommendations for primary prevention of allergic diseases until results of prospective studies allow to consider a more precise behaviour. In contrast, subjects sensitized and exposed to allergens present an increased risk to develop asthma or non specific bronchial hyperreactivity. Therefore, secondary prevention appears as an essential method for treatment of allergic disease, with clinical benefits on symptoms which have recently been demonstrated in a clinical study.
La Revue du praticien 07/2005; 55(12):1299-304.
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ABSTRACT: Anaphylactic reactions caused by bites of the European pigeon tick Argas reflexus are repeatedly reported. This soft-backed tick is a parasite of wild pigeons colonizing urban buildings and houses. Occasionally the ticks can bite human beings, inducing anaphylactic reactions in sensitized patients.
Our aim was to characterize the major allergen implicated in a series of anaphylactic reactions caused by Argas bites and to produce the allergen as recombinant protein for diagnostic purposes.
Protein extracts were prepared from whole A reflexus bodies, and IgE immunoblots were performed with sera from 13 patients who had an anaphylactic reaction with pigeon tick bites. A cDNA expression library was constructed from whole ticks and screened with a polyclonal rabbit antiserum raised against the major allergen.
The cDNA coding for the dominant allergen Arg r 1 could be isolated. It encodes a protein belonging to the lipocalin family. Allergenicity of the recombinant Arg r 1 was confirmed by immunoblot, ELISA, and intradermal skin tests.
The dominant allergen of A reflexus has been isolated and the corresponding cDNA cloned. The recombinant protein, a lipocalin, was expressed in Escherichia coli and was shown to be immunoreactive in vitro and in vivo. Recombinant Arg r 1 was used as a diagnostic tool in a series of anaphylactic reactions caused by pigeon tick bites.
Journal of Allergy and Clinical Immunology 04/2005; 115(3):617-22. · 11.00 Impact Factor
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Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 03/2005; 94(2):308-9. · 2.83 Impact Factor
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ABSTRACT: Epidemiological surveys indicate that there has been a notable increase in the prevalence of asthma and other allergic diseases in children and adults. The purpose of this review is to report and comment on recent studies about the role of allergen in primary prevention and to seek new insights on the effects of allergen control in allergic patients.
This paper deals with allergen reduction in primary prevention, the effect of early exposure to pets on atopic diseases and the development of new occupational activity improving allergen control in allergic patients.
The role of allergen dose involved in the onset of atopy is controversial. Studies hypothesizing that a reduction of allergen dose might reduce atopy failed to confirm the data from the Isle of Wight study and found no effect on the frequency of immunoglobulin E sensitization. This effect might nonetheless occur later in life. Other studies indicate that high doses of allergen early in life have a protective effect against cat and dog sensitization. Only one retrospective study found that cat exposure was protective against cat sensitization. A German prospective study suggested, however, that it is more probable that cat allergen exposure is harmfully related to sensitization, by increasing IgE synthesis. The effect of high doses must be clarified by further prospective studies. Accordingly, we must be very careful when giving advice on primary prevention, particularly about the protective effect of cat and dog allergens. Secondary prevention may be dramatically improved with the help of a new occupational activity: the medical indoor environment counsellor.
Current Opinion in Allergy and Clinical Immunology 07/2003; 3(3):165-8. · 4.11 Impact Factor
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ABSTRACT: Our aim was to compare bronchial responses to major cat allergen (Fel d 1) in individuals with intermittent asthma sensitized to cats (19 subjects) according to the droplet particle size. We used three nebulizers, which delivered particles with mass median aerodynamic diameters of 1.4, 4.8, and 10.3 microm. A dosimeter nebulizer was used. The cat allergen was diluted to obtain the same amount of Fel d 1 per puff with each nebulizer. Each patient underwent three methacholine bronchial challenge tests (BCT), each followed 24 hours later by a cat allergen BCT, each performed with a different nebulizer (randomly selected each time, with patient and tester always blinded). Subjects did not differ for methacholine responsiveness, FEV1, mean forced expiratory flow during the middle half of the FVC (FEF25-75), PEF, or dyspnea (Borg scale) before any of the three cat BCTs. Cat allergen PD20 was 271 ng of Fel d 1 with the 1.4 microm nebulizer, 46 ng with the 4.8 microm nebulizer, and 13.5 ng with the 10.3 microm nebulizer (p = 0.00001). Inhalation of small particles (1.4 microm) resulted in significantly lower FEF25-75 24 hours after provocation than large particles did. In conclusion, immediate bronchial response appears to be localized in large airways, and the use of large particles is more appropriate for cat allergen BCTs.
American Journal of Respiratory and Critical Care Medicine 05/2003; 167(8):1077-82. · 11.08 Impact Factor
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Frédéric de Blay
La Revue du praticien 06/2002; 52(9):1017-31.
