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Y Delneste

Publications and source records attributed to Y Delneste.

49 records · Page 3Linked to original sources
PubMed1994

Abnormal IgG4 antibody response to aeroallergens in allergic patients.

Various studies have suggested the involvement of immunoglobulin G4 (IgG4) antibodies (Ab) in the physiopathology of allergic disorders. Recently, an abnormal IgG4 Ab production in response to immunization has been reported in some atopic patients. Thus, in order to evidence in allergic patients, a potential abnormal IgG4 Ab response to aeroallergens following natural exposure, we compared, in 34 patients sensitive to Dermatophagoides pteronyssinus and in 16 healthy subjects, the IgG4 Ab response to D. pteronyssinus, grass pollen and cat dander, using a solid-phase radioimmunoassay. Since some patients were also sensitive to grass pollen and/or to cat dander, we analyzed, in all patients, the IgG4 Ab responses both towards the allergen(s) they were sensitive to (sensitizing allergen) or not (unrelated allergen). The results showed that 90% of the patients produced levels of antisensitizing allergen(s) IgG4 Ab significantly higher than the controls; this IgG4 Ab response was correlated with the corresponding specific IgE Ab level. In addition, among these patients, around 40% presented high levels of IgG4 Ab to the unrelated allergen(s). Thus, in allergic patients, while specific IgE Ab define the nature of the sensitizing allergen, the presence of IgG4 Ab directed against various allergens seems in relation with an abnormal isotype regulation associated with atopic disorders.

Adolescent↗
PubMed1993

T and B cell immune response to a 55-kDa endothelial cell-derived antigen in severe asthma.

Current concepts on the pathogenesis of chronic asthma emphasize the role of several inflammatory cell populations and their respective mediators that interact in a complex network. However, beside inflammatory cells, lymphocytes are also present in asthmatic airways. Although little is known about their involvement in asthma, it has been suggested that lymphocytes may participate in the development of chronic inflammation either through lymphokine secretion or through antibody production. In this study, we describe circulating IgG autoantibodies, directed against a common 55-kDa antigen shared by platelets and cultured endothelial cells, and found in 34 out of 97 asthmatic patients. Among epidemiological, clinical and biological characteristics of these asthmatic patients, the anti-55-kDa antigen antibodies are mainly restricted to patients with negative cutaneous prick tests (p = 0.0014), and corticosteroid-dependent asthma (p = 0.0036). These antibodies were also detected in a few patients with autoimmune disorders like systemic lupus erythematosus (3/30) or rheumatoid arthritis (2/36). Both platelet and endothelial cell antigens were cross-reactive, had an isoelectric point between 8.0 and 9.0, were insensitive to reducing agents such as 2-mercaptoethanol, and were not present on either platelet or endothelial cell surface, as determined by immunostaining assay. [3H]Thymidine incorporation assay with peripheral blood mononuclear cells from patients in the presence or in the absence of 55-kDa antigen, purified from nitrocellulose sheets demonstrated a specific incorporation in 6 out of 13 patients with circulating anti-55-kDa antigen antibodies, with index values ranging from 12 to 3. Such a T cell reactivity has also been observed in 3 out to 17 patients without detectable serum anti-55-kDa antigen antibodies. Moreover, a significant correlation was found between index values of antigen-specific T cell reactivity and the forced expiratory volume in one second (r = 0.544, p = 0.003). Our data indicate that the detection of such antibodies allows to distinguish a subgroup of asthmatics in terms of severity and to suggest a relationship between clinical severity and T and B cell autoreactivity to the 55-kDa platelet/endothelial cell antigen.

Adult↗
PubMed1993

Production of anti-endothelial cell antibodies by coculture of EBV-infected human B cells with endothelial cells.

Vascular endothelial cells are suspected of being the target of autoimmune processes seen in many connective tissue diseases and in systemic vasculitis as evidenced by the detection of circulating autoantibodies against endothelial cell antigens. In order to select B cells recognizing endothelial cells antigens, Epstein-Barr virus (EBV)-infected B cells, obtained from one patient presenting a systemic vasculitis, were cocultured with human endothelial cells concurrently with a human endothelial cell line (EC-pSV1 cells). This coculture consisted of a first step of expansion of B cells specifically selected by adherence onto human umbilical vein endothelial cells (HUVEC). The adherence of selected B cells was specific to endothelial cells because no rosette formation around control cells (HeLa cells or COS cells) was observed. Adherent B cells were cloned by limiting dilution by coculture onto EC-pSV1 cells and screened for anti-HUVEC antibody production by endothelial cell ELISA. An increase in anti-HUVEC antibody production of IgM isotype was detected by endothelial cell ELISA, peaking at Day 9 and remaining constantly elevated, relative to B cell expansion. Among 21 B cell lines producing IgM, 6 presented high levels of anti-HUVEC antibodies, whereas 1 of 52 B cells cloned without EC-pSV1 cells showed such antibody production. Anti-HUVEC antibody production and B cell proliferation were dependent on the presence of endothelial cells. Two of these 6 B cell lines produced antibodies directed against an endothelial cell antigen with an apparent molecular weight of 192 kDa as determined by immunoblotting analysis. Our results demonstrate that adherence of EBV-infected B cells to endothelial cells and further cloning by adherence can efficiently select anti-HUVEC antibody-producing human B cells and might help to define antigens potentially involved in autoimmune diseases.

Antibody Formation↗
PubMed1993

Interleukin-6 and interleukin-1 alpha production is associated with antigen-induced late nasal response.

BACKGROUND: Cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-6 and granulocyte macrophage-colony stimulating factor (GM-CSF) are able to potentiate allergic inflammation and seem to be implicated in the development of the late allergic reaction. METHODS: To study the time course of cytokine production, sequential lavages were performed after nasal allergen challenge. Thirteen patients with allergic rhinitis and four healthy subjects were exposed to grass pollen (n = 6 and n = 2, respectively) or dust mite allergen (n = 7 and n = 2, respectively). RESULTS: Among the patients with allergic rhinitis, a single early response (single responders) developed in four, eight exhibited a dual response (dual responders) and one patient as well as the four healthy subjects did not respond. In addition to the measurement of IL-1 alpha, IL-6, TNF-alpha and GM-CSF concentrations by ELISA, the release of histamine, tryptase, and eosinophil cationic protein was also evaluated by radioimmunoassay performed on nasal lavage fluids. Concerning mediator levels in nasal lavage fluid, neither histamine release nor cytokine elevation were noted in healthy subjects. As previously described, histamine, tryptase and eosinophil cationic protein were released in single and dual responders. Concerning cytokines, TNF-alpha was undetectable in the majority of nasal lavages and an increase in GM-CSF concentration was occasionally observed whatever the type of response. In contrast, an increase in IL-1 alpha and IL-6 levels was observed for dual responders during the early period (12.6 +/- 3 and 9.2 +/- 2 pg/ml, respectively; p < 0.01 in both cases) and at a higher level during the late period (14.5 +/- 4, p not significant and 16.7 +/- 8 pg/ml, respectively; p < 0.01) when compared with baseline values (7.2 +/- 2.2 and 2 +/- 0.7 pg/ml, respectively). For single responders IL-1 alpha and IL-6 secretion was detected mainly during the early period. CONCLUSION: These data suggest a role for IL-1 alpha in the induction and perennisation of the inflammatory reaction in allergic rhinitis, whereas the role of IL-6 remains to be investigated.

Adult↗
PubMed1993

Immunogenicity and antigenicity of synthetic peptides derived from the mite allergen Der p I.

As an immunogen must contain both B- and T-cell epitopes, small peptides are usually reported as non-immunogenic unless coupled to a protein carrier. In this study, the immunogenicity of the Der p I synthetic uncoupled peptides (p52-71, p89-104, p117-133 and p176-187) previously reported as B-cell epitopes, was evaluated. Different schedules of immunization were used. Results indicated that by using the Vaitukaikis' method three injections of the same peptide without protein carrier was sufficient to induce an specific anti-peptide IgG antibody response (evaluated by ELISA). Indeed, the 16-20 amino-acid long peptides p52-71, p117-133 and p89-104 were revealed highly immunogenic in rabbits. Furthermore anti-peptide p52-71 and p117-133 antibodies were shown by Western-blotting or by neutralization assay to recognize the Der p I molecule either in denaturated or native form as well as Der f I (major allergen of Dermatophagoides farinae). Finally, taking into account the location of Der p I-derived peptides in the three-dimensional model of Der p I, the antigenicity and immunogenicity of peptides were discussed.

Allergens↗
PubMed1993

Modulation of adhesion molecule expression on endothelial cells during the late asthmatic reaction: role of macrophage-derived tumour necrosis factor-alpha.

In a previous work we have demonstrated that in patients exhibiting a late allergic reaction (LAR), alveolar macrophages (AM) collected 18 h after bronchial allergen challenge produced high levels of IL-6 and tumour necrosis factor-alpha (TNF) which is known to up-regulate the endothelial cell expression of adhesion molecules participating in the development of the inflammatory reaction in bronchial asthma. For these reasons, we evaluated the effect of AM supernatants from asthmatic patients developing an LAR on intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) expression by human endothelial cells. The expression of adhesion molecules was assessed by an ELISA method and compared with the effect of an optimal dose of human recombinant (hr) TNF. Results showed that AM supernatants, from challenged asthmatics developing an LAR, increased significantly the ICAM-1 and ELAM-1 expression on endothelial cells to a level similar to that obtained in the presence of hrTNF (500 U/ml) (P < 0.001 in both cases, respectively 90.4% and 75.2% of the level obtained with hrTNF). In contrast, AM supernatants from asthmatics at baseline or exhibiting, after challenge, a single early reaction had no significant effect on these parameters (P = NS in both cases, respectively 23.5% and 24.7% of the ICAM-1 expression, 22.7% and 15.3% of the ELAM-1 expression obtained with hrTNF). AM-derived TNF present in these supernatants was thought to play a key role in endothelial cell stimulation, since: (i) TNF concentration in AM supernatants correlated with its effect on ICAM-1 (r = 0.80, P < 10(-4)) and ELAM-1 expression (r = 0.88, P < 10(-5)); and (ii) a neutralizing anti-TNF antibody decreased their effect (68% and 80% respectively on ICAM-1 and ELAM-1 expression). Moreover, the role of IL-6 was excluded on the basis both of the hrIL-6 inefficiency to induce ICAM-1 and ELAM-1 synthesis, even in costimulation with hrTNF, and of anti-IL-6 antibody to neutralize the effect of AM supernatants. Our results suggest that, beside mast cells and lymphocytes, macrophages might participate in the induction of the local inflammatory reaction observed in bronchial asthma. During the LAR, cytokines and especially TNF are able, through an enhanced adhesion molecule expression on endothelial cells, to facilitate the bronchial cellular influx.

Asthma↗
PubMed1993

Role of endothelial cells in the pathogenesis of bronchial asthma.

Endothelial cells appear to play a dual role in the pathogenesis of bronchial asthma. These cells participate in recruitment of leukocytes to the site of the allergic response by releasing neutrophil chemotactic factors and modulating leukocyte-adhesion molecules. Enhanced expression of adhesion molecules has been detected in endothelial cell cultures subjected to various types of stimuli, including such cytokines as tumor necrosis factor alpha and interleukin-1 beta. In addition, there is evidence to suggest that antibodies directed against an endothelial cell component may also contribute to the inflammatory processes associated with severe asthma.

Asthma↗
PubMed1992

Human endothelial cells transfected by SV40 T antigens: characterization and potential use as a source of normal endothelial factors.

A putative role for the vascular endothelium as target for autoantibodies has been suggested in several autoimmune disorders and connective-tissue diseases. However, there are some difficulties linked to the use of cultured endothelial cells (EC) that limit considerably the extensive studies on the nature of endothelial target antigens involved. To overcome this problem, human EC, derived from umbilical veins, were transfected with recombinant plasmid pSV1 which contained the early genes of simian virus SV40. These transfected cells, called EC-pSV1, are able to grow without EC growth supplement and demonstrate a population doubling time of about 50 h. Among the EC properties, EC-pSV1 retain intracellular content of angiotensin-converting enzyme activity, exhibit constitutive production of interleukin 6 and of a growth-promoting activity on early passage EV, express intercellular adhesion molecule 1 (ICAM-1) and its up-regulation by tumor necrosis factor alpha, but have lost the expression of factor VIII-related antigen. Moreover, EC-pSV1 express a 55-kDa antigen found on EC and human platelets, and presumably acting as an antibody target in some cases of non-allergic asthma. However, at the 50-55th generation, morphological changes and altered growth behavior were visible. This work demonstrates that transfection of EC with SV40 T antigens may be of interest, particularly in areas of research including the study of EC targets involved in different human diseases.

Antigens, Polyomavirus Transforming↗
PubMed1992

Specific histamine release capacity of peptides selected from the modelized Der p I protein, a major allergen of Dermatophagoides pteronyssinus.

Dust mite allergens are considered as a major cause of allergic disease and as a risk factor for asthma. Der p I, a 222 amino-acid residue globular glycoprotein, is one of the major allergens from Dermatophagoides pteronyssinus (Dpt) mites. In this study, we have used predictive conventional algorithms (i.e. hydrophilicity, mobility, accessibility) and a three-dimensional model of Der p I derived from comparison to actinidin and papain to select continuous amino acid sequences as potential B cell epitopes. Four peptides, 52-71, 117-133, 176-187, 188-199 were synthesized. Their antigenic reactivity was investigated, mainly by measuring their capacity to induce in vitro histamine release. Results indicated that only Dpt-sensitive patients react specifically to Der p I-derived peptides and more frequently to 52-71 and 117-133. For each peptide, the intensity of response was dependent on the patient tested and on the peptide concn. The capacity of peptides to induce histamine release was demonstrated to be correlated with the serum level of anti-Der p I IgE (r = 0.86; p less than 10(-2)). Taken together these data emphasize, in Dpt-sensitive patients, the heterogeneity of the specific response to synthetic Der p I-derived peptides and underline the possible variety of epitopes belonging to the allergen Der p I.

Allergens↗
PubMed1992

Levels of soluble IL-2 receptor in plasma from asthmatics. Correlations with blood eosinophilia, lung function, and corticosteroid therapy.

Evidence now suggests that eosinophils and T lymphocytes infiltrating bronchial tissues may play a key role in the pathophysiology of asthma. Circulating eosinophils, lung function, and plasma soluble IL-2 receptor (sIL-2R) were measured in 42 asthmatic patients referred for symptomatic asthma. The patients were divided into two groups based on the presence or absence of atopy. The group of non-atopic asthmatics was further divided according to the patients' requirement for long term oral corticosteroids. The mean sIL-2R +/- s.d. was 36.3 +/- 9.9 pM in the control group, 28.9 +/- 9.2 pM in the atopic asthmatics, 43.3 +/- 18.07 pM in the non-atopic asthmatics without oral steroid therapy, but was increased in the steroid-treated group (62.2 +/- 19.3 pM, P less than 0.01). A significant correlation was found between FEV1 and circulating eosinophils in atopic asthmatics and in non-atopic asthmatics without oral corticosteroid therapy, but not in the steroid-treated group. Furthermore, significant correlations were found between sIL-2R and FEV1, and between sIL-2R and blood eosinophils, in the group of non-atopic asthmatics not on oral steroid therapy. No such correlations were evidenced in the other groups of asthmatics. Similar results were obtained during the clinical course of three non-atopic patients followed for more than 1 year. These data suggest that T cell activation appears more prominent in non-atopic asthma than in atopic asthma. Moreover, it appears that T cell activation can occur in severe forms of asthma despite steroid treatment. Finally, the results suggest a possible link between T cell activation, eosinophils, and lung function, which may reflect a particular pathogenetic mechanism involved in non-atopic asthma.

Adrenal Cortex Hormones↗
PubMed1991

Potential implication of endothelial cells in bronchial asthma.

Inflammatory cells like eosinophils, neutrophils or mononuclear phagocytes have long been recognized as essential components in the pathophysiology of asthma. After recruitment in situ and subsequent activation, they are considered as responsible for epithelial and submucosal bronchial alterations. However, to access to the inflammatory site, these cells have to cross the endothelial wall, suggesting so a potential implication of endothelial cells (EC) in bronchial asthma. To test this hypothesis, we studied in a first step the modulation of vascular adhesions like intercellular adhesion molecule-1 (ICAM-1) on EC: supernatants of alveolar macrophages (AM) recovered by bronchoalveolar lavage in patients exhibiting a late asthmatic reaction, induced an enhanced expression of ICAM-1 on EC preparations; increase of ICAM-1 was clearly correlated to amounts of tumor necrosis factor-alpha (TNF alpha) present in AM supernatants, as shown by inhibition experiments with anti-TNF alpha antiserum. The second way to explore the possible role of EC in asthma was the detection of autoantibodies to EC in various allergic disorders: antibodies against a 120-kD EC antigen in patients with allergic granulomatosis and angiitis, antibodies towards a 55-kD component, common to human EC and platelets in patients with severe asthma, namely characterized by their corticosteroid dependence or by aspirin-induced intolerance. So our data suggest that bronchial asthma might result from either EC activation, through the induction of surface adhesion molecules or from an autoimmune process involving EC antigens.

Adolescent↗
PubMed1991

Neutrophil-endothelial cell interaction: evidence in vitro for a regulation by endothelial cells of neutrophil functions.

The purpose of this study was to investigate a possible relationship between human umbilical vein endothelial cells (EC) triggered by ionophore A23187 at different doses (0.5-2.5 microM) and polymorphonuclear neutrophils (PMN). EC supernatants were shown to contain neutrophil chemoattractant activity (NCA) and in parallel a factor inducing an inhibition of PMN chemiluminescence (PMN CL). Supernatants obtained from EC triggered by A23187 exhibited a high level of NCA (73 +/- 5 PMN.hpf-1 compared to 21 +/- 4 PMN.hpf-1 in untreated EC supernatants, p less than 0.01). This NCA was independent from arachidonic acid metabolites, since indomethacin and nordi-hydroguaiaretic acid failed to suppress the chemotactic activity. Using gel filtration chromatography (AcA 54) the NCA was recovered in a single peak of apparent molecular weight of 37,000 +/- 4,000 daltons. Checkerboard analysis indicated that NCA exhibited both chemotactic and chemokinetic activities. In addition, supernatants of A23187-stimulated EC, and at a lesser degree, supernatants of unstimulated EC, inhibited PMN CL induced by N-formyl-Methionyl-Leucyl-Phenylalanine (61% inhibition, p less than 0.05), and by A23187 itself (80% inhibition, p less than 0.01), but not that induced by phorbol-myristate-acetate. Indomethacin and protamine sulphate did not modulate this inhibitory activity. By contrast, EC-derived inhibitory activity was inhibited (50%) by an adenosine antagonist (8-phenyltheophylline), indicating a participation of adenosine in this inhibitory activity of PMN CL. These data suggest the possibility that activated endothelial cells could both enhance PMN migration and protect themselves against potential damaging effects of oxygen metabolites produced by PMN, particularly during transvascular migration.

Calcimycin↗