Biomedical subjects

B Gossart

Publications and source records attributed to B Gossart.

11 recordsLinked to original sources

PubMed2000

Early effect of ultrarush venom immunotherapy on the IgG antibody response.

BACKGROUND: We have previously shown in several allergy models that allergic and tolerance status with respect to allergens is associated with a somewhat different dominant specificity of IgG antibodies. The objective was to test this hypothesis in the compelling model of ultrarush venom immunotherapy (VIT), which induces clinical tolerance after only a few hours of treatment. METHODS: Antibody titers and specificity were evaluated through solid-phase ELISA using streptavidin-biotin technology in 12 patients allergic to wasp venom before and during the ultrarush procedure (at 12 h, 24 h, and 15 days). The results were compared with those from another group of 20 patients treated with venom injections for at least 2 years. RESULTS: No significant change was observed in IgG titers during the early phase of VIT. The capacity of individual sera to prevent the antigen binding of pooled IgG from allergic patients changed rapidly, with mean percentage inhibitions falling from 80+/-15%, before starting VIT, to 26+/-14%, 35+/-15%, and 34+/-5% after 12 h, 24 h, and 15 days of treatment, respectively (P<0.001 by one-way ANOVA). The capacity of individual sera to prevent the antigen binding of pooled IgG from patients receiving prolonged VIT changed, with mean percent inhibitions increasing from 47+/-8%, before starting VIT, to 76+/-7%, 83+/-6%, and 87+/-6% after 12 h, 24 h, and 15 days of treatment, respectively (P<0.001 by one-way ANOVA). CONCLUSIONS: During the initial phase of ultrarush VIT, a change in IgG specificity, i.e., a change in the set of epitopes dominantly recognized by IgG on wasp-venom antigens, occurred concomitantly with early clinical tolerance and was already detectable a few hours after the onset of treatment. Although it may be an epiphenomenon, this change represents the earliest humoral modification described so far during this procedure. The mechanism is unknown, but it appears to be a selective depletion of the highest avidity antibody fraction by the venom injected in large doses at this stage of therapy. Finally, our data now show the previously documented association between a particular IgG specificity and the clinical status (allergy vs tolerance) to be true also with ultrarush VIT, a model in which the clinical ability to display allergic symptoms is rapidly reversed.

Adult↗

PubMed1999

Relationship between allergic status and specificity of IgG antibody to inhaled allergens: the grass pollen model.

BACKGROUND: We have previously reported that IgG antibodies from healthy individuals and patients suffering from non-seasonal mite allergy bind to different sets of epitopes on Der p 1, allowing almost complete discrimination of the populations. OBJECTIVES: To confirm this observation in a seasonal allergy model where a clear relationship between allergic symptoms and exposure to the offending agent is established. To investigate whether the pattern of modified specificity is related to the differences in IgG subclass hierarchy usually exhibited by nonallergic and allergic populations. METHODS: The capacity of individual sera from patients allergic to grass pollen and healthy individuals, including grass pollen-sensitized subjects, to prevent the binding of pooled IgG, IgG1, and IgG4 fractions from grass pollen-allergic patients and healthy individuals to solid-phase bound grass pollen antigen was evaluated in enzyme-linked immunosorbent assay (ELISA) using streptavidin-biotin technology. Specificity controls were performed using sera from patients allergic to cat dander and house dust mite. RESULTS: The capacity of sera to prevent the antigen binding of allergic IgG averaged 84 +/- 5% for allergic sera and 53 +/- 6% for healthy sera (P < 0.001 by one-way anova). Conversely, using the antigen-binding capacity of healthy control IgG as reference, percentage inhibitions averaged 46 +/- 9% in grass pollen-allergic subjects compared with 80 +/- 4%, 82 +/- 2% in healthy individuals, and mite- and cat-allergic patients, respectively, resulting in two well-separated populations (P < 0.0001 by one-way anova). Similar results were found regardless of whether pooled IgG1 or IgG4 were used. CONCLUSION: Together with previous data, our results define a new type of humoral signature in the immune response to inhaled allergens. Allergic and healthy status differ not only in the presence or absence of specific IgE antibody but also in the preferential expression of distinct IgG specificities that are better correlated with clinical manifestations and are unrelated to subclass distribution.

Adult↗

PubMed1998

Modified antigenic reactivity of anti-phospholipase A2 IgG antibodies in patients allergic to bee venom: conversion with immunotherapy and relation to subclass expression.

BACKGROUND: We have previously reported that, in addition to modifying IgG levels and subclass distributions, wasp venom immunotherapy (VIT) rapidly changes IgG antibody specificity. OBJECTIVES: We investigated whether such a change can be documented in the IgG response to the major bee venom allergen, phospholipase A2 (PLA2), from patients allergic to bees treated with VIT; whether it is coupled to the shift in IgG subclass distribution (IgG4 predominance) usually observed during VIT; and whether it restores the specificity displayed by IgG antibodies from nonallergic individuals. METHODS: Antibody specificity was evaluated in 17 patients allergic to bee venom in competitive ELISAs by using streptavidin biotin technology. Patients were tested before and during specific immunotherapy (at 15 days and 6 months) and compared with another group of 17 patients treated with venom injections for at least 2 years (VIT patients) and 30 healthy individuals. RESULTS: The capacity of individual sera to prevent PLA2 binding of pooled IgG from allergic patients changed rapidly with mean percentage inhibitions falling from 84% +/- 14% before starting VIT to 27% +/- 13% and 28% +/- 7% after 15 days and 6 months of treatment, respectively (p < 0.001 by one-way analysis of variance [ANOVA]). IgG titers were only slightly increased. The capacity of individual sera to prevent the binding of pooled IgG from patients receiving VIT changed rapidly with mean percentage inhibition increasing from 60% +/- 12% before starting VIT to 85% +/- 6% and 82% +/- 6% after 15 days and 6 months of treatment, respectively (p < 0.001 by one-way ANOVA). Similar results were found regardless of whether pooled IgG1 or pooled IgG4 were used. CONCLUSION: VIT results in a rapid change in the antigenic reactivity of anti-PLA2 IgG antibody of human allergic sera, restoring, although not completely, the specificity peculiar to lgG from healthy individuals. This suggests that allergic status and immunoprotection correlate with the preferential expression of distinct IgG specificities, which appear equally distributed over the IgG1 and IgG4 antibody subclasses. It is, however, not known whether the shift in IgG specificity is one of the operative mechanisms of VIT.

Adult↗

PubMed1998

Anti-betalactoglobulin IgG antibodies bind to a specific profile of epitopes when patients are allergic to cow's milk proteins.

BACKGROUND: We demonstrated recently that mite-allergic patients differed from healthy controls in the specificity of their IgG antibodies towards mite antigens. OBJECTIVE: The present study investigates whether these discriminatory IgG responses could be associated with the expression and the evolution of clinical manifestations in allergy to cow's milk proteins. METHODS: Antibody specificity was evaluated by comparing IgG-binding to native bovine beta-lactoglobulin (nBLG) and its products of pepsin hydrolysis (dBLG) using a solid-phase enzyme-linked immunosorbent assay (ELISA). Antibody specificity was further investigated in competitive ELISA using streptavidin-biotin technology with purified IgG fractions from selected subjects and specific mouse monoclonals raised against BLG. RESULTS: IgG antibodies from CM-intolerant or allergic sera (n=222) showed a higher degree of binding to nBLG than to dBLG, while control sera showed similar levels to both nBLG and dBLG (n=99 children/65 adults). Sera from symptomatic patients, wether or not they contained IgE antibodies, demonstrated group-segregating capacities to compete with pooled purified IgG from each clinical class, and with selected murine anti-nBLG monoclonal antibodies for binding to n- and dBLG. Furthermore, this inhibitory capacity shifted dramatically in a small subset (n=14) of children as they developed CM-tolerance. CONCLUSIONS: The IgG responses to BLG of CM-intolerant or allergic patients are very different from those of healthy controls, being characterized not only by increased titres but also similar patterns of modified specificity, including a marked preference for conformational epitopes. Cross-competition experiments confirmed that the restricted specificity was clinically associated, appearing as an immunological signature, which allowed almost complete discrimination between patient groups. This phenomenon is a particularly promising diagnostic feature in this category of young patients where conventional tests usually only document the status of sensitization.

Adult↗

PubMed1997

Wasp venom immunotherapy changes IgG antibody specificity.

BACKGROUND: The evolution of the IgG response during venom immunotherapy (VIT) has been previously investigated in terms of antibody titres and subclasses. OBJECTIVES: The present work studied the evolution of IgG antibody fine specificity in wasp allergic patients treated with rush VIT. METHODS: Antibody specificity was evaluated in 51 wasp allergic patients in competitive ELISA using streptavidin biotin technology. Patients were tested before and during specific rush immunotherapy (at 15 days, 6 months, 12 months) and compared with 44 patients treated by venom injections for at least 2 years. RESULTS: The capacity of sera to prevent the antigen binding of pooled IgG from allergic patients changed rapidly with mean percentage inhibitions (+/-SD) falling from 70+/-11-51+/-18% after 15 days of treatment (P<0.001 by one way ANOVA). Similarly, the antigen binding capacity of pooled IgG from VIT patients was differently prevented by sera with mean percentage inhibitions increasing from 37+/-12-65+/-8 after 15 days of treatment (P< 0.0001 by one-way ANOVA). CONCLUSIONS: The immunodominance pattern of IgG epitopes recognized on wasp venom antigens by sera from wasp allergic patients changes soon after initiating rush VIT. Further studies will indicate whether, instead of measuring IgG titres, this marked change could be used as the basis of a new test for monitoring the outcome of VIT.

Adolescent↗

PubMed1996

Fine tuning of epitopic dominance induced by lung cancer on the IgG response to bovine betalactoglobulin: towards a paraneoplastic immune marker.

BACKGROUND: Investigating the humoral immune response to mucosal antigens in patients with lung cancer, we have documented a preferential immunoglobulin G (IgG) binding to cryptic epitopes unmasked by the proteolysis of bovine beta-lactoglobulin (BLG). In contrast, IgG from healthy controls and patients with chronic bronchitis (COPD) bind preferentially to continuous epitopes presented on both native (n) and denaturated (d) forms of this antigen. The present study further characterized the differences in the epitope profiles recognized on BLG. METHODS: The capacity of individual sera from 65 lung cancer patients, tested before and after cancer removal for the patients with early stage lung carcinoma, 65 healthy controls, and 52 patients with COPD, to prevent the binding of pooled IgG fractions from each population as well as murine monoclonal antibodies (MoAb), specific for BLG, to solid phase bound antigen was evaluated in enzyme-linked immunoadsorbent assay using streptavidin-biotin technology. Some of these experiments were also performed with sera from 42 patients diagnosed with other cancers. RESULTS: Compared with control sera and sera from patients with other solid tumors, lung cancer patient sera showed distinct capacities to prevent the binding of murine MoAb as well as human pooled IgG fractions to n- and d-BLG. The inhibition capacities of lung cancer sera changed as soon as five weeks after cancer removal. CONCLUSIONS: The results indicate that the difference in epitope specificity exhibited by lung cancer sera is not restricted to cryptic epitopes, but also affects continuous and discontinuous epitopes, accessible only on the native antigen. A high level of binding discrimination between antibodies from the study populations is also observed at the level of the epitope. This deviation in the epitope specificity of antibodies changes soon after cancer removal, suggesting a tumor-dependent disturbance. Also documented in the Dermatophagoides pteronyssinus model, it opens the way to a new class of paraneoplastic immune markers for this malignancy, with, at first glance, a high specificity level.

Adenocarcinoma↗

PubMed1995

Lung cancer-related changing profile of B-cell epitopes recognized on mucosal antigens: the Der p1 model.

BACKGROUND: The natural immunoglobulin G (IgG) response towards antigens presented at the mucosal level in patients with lung cancer, the most frequent mucosal malignancy in humans was studied. Compared with healthy control subjects, patients with lung cancer display lower IgG antibody titers toward antigen p1 of the house dust mite, Dermatophagoides pteronyssinus (Der p1), chronically presented to the respiratory mucosa. The present study further characterizes this defect in terms of antibody specificity. METHODS: Antibody specificity was studied by comparing the IgG binding to native Der p1 (nDer p1) and its products of pepsin hydrolysis (dDer p1) in a solid phase enzyme-linked immunosorbent assay (ELISA) in 148 patients with lung carcinoma, 148 healthy control subjects, and 50 patients with chronic bronchitis. Antibody specificity was also evaluated before and after (5 +/- 1 weeks) surgical excision of the tumor in competition ELISA using streptavidin-biotin technology. RESULTS: Lung cancer sera had a higher degree of binding to dDer p1 compared with nDer p1, whereas control group sera bound similarly to the two forms of the antigen. Lung cancer sera and control group sera showed distinct capacities to prevent the binding of pooled IgG from each group to nDer p1. The inhibition capacity displayed by cancer sera is changed 5 weeks after cancer removal. CONCLUSION: These results, somewhat similar to those observed for bovine betalactoglobulin, document the recognition of a different set of epitopes on Der p1 and more generally on mucosal antigens by lung cancer IgG compared with the IgG from control patients. This distinct profile of epitope specificity changes partially soon after cancer removal, suggesting a tumor-dependent disturbance and opens the way to a new class of markers in lung cancer. Furthermore, this study documents a surprising but striking influence of the clinical status on the choice of B-cell immunodominant epitopes in mucosal responses.

Adult↗

PubMed1993

A different profile of epitopic dominance in the immunoglobulin G response to bovine betalactoglobulin in lung cancer.

BACKGROUND: The authors previously documented a quantitative defect in the immunoglobulin G (IgG) response toward bovine betalactoglobulin (BLG), the major cow's milk antigen, and antigen p1 of the house dust mite, Dermatophagoides pteronyssinus (Der p1), in patients with lung cancer. In the Der p1 model, the authors documented at the IgG level an epitope specificity that differed between patients with lung cancer (preferential specificity for cryptic epitopes) and healthy control subjects and patients with mite allergy. The current study investigated whether this varying specificity might be extended to the IgG response toward BLG. METHODS: The authors compared the IgG binding to native BLG (nBLG) and its products of pepsin hydrolysis (dBLG) in a solid-phase enzyme-linked immunosorbent assay (ELISA) using peroxidase-conjugated protein A in 120 patients with lung cancer, 52 patients with chronic obstructive pulmonary disease (COPD) who were closely matched for age, sex, and smoking habits with the patients with cancer, and 120 healthy control subjects (blood donors). RESULTS: Expressing the ratio between optical densities observed for dBLG and nBLG, respectively, the authors documented two groups: patient with lung cancer with higher levels of binding on dBLG (mean ratio +/- SD, 1.66 +/- 0.26) and healthy control subjects and patients with COPD with similar levels of retention for dBLG and nBLG (mean ratios +/- SD, 1.00 +/- 0.10 and 1.01 +/- 0.07, respectively). Influence of population characteristics could be excluded. The histologic type of cancer and its extent had no influence on the defined ratio. CONCLUSION: These results suggest a preferential recognition of epitopes unmasked by pepsin hydrolysis (cryptic epitopes?) by lung cancer IgG, contrasting with the preferential specificity of IgG from healthy control subjects and patients with COPD for structural epitopes unaffected by the proteolysis. These findings are similar to those observed previously with Der p1 and indicate a varying, and possibly specific, profile of epitopic dominance in the IgG response to antigens naturally presented at the mucosal level in patients with lung carcinoma, a model of mucosal cancer.

Adult↗

PubMed1993

Antibody affinity disturbance in the immunoglobulin immune response to mucosal antigenic stimulation in lung cancer. The Betalactoglobulin Model.

BACKGROUND: This study is a continuation of a recent study, in which a defect in the immunoglobulin G (IgG) response to some natural antigens (bovine betalactoglobulin [BLG] from cow's milk and antigen p1 from the house dust mite Dermatophagoïdes pteronyssinus), usually presented at the mucosal level, was documented in lung cancer patients. The present study further characterizes this difference in terms of antibody relative functional affinity in the BLG model. METHODS: Relative functional affinity was evaluated by solid-phase enzyme-linked immunosorbent assay in terms of the relationship between specific IgG retention, assessed with peroxidase-labeled protein A, and serial dilutions of IgG fractions isolated from 24 sera from lung cancer patients and 24 sera from healthy control subjects matched for their anti-BLG IgG antibody titers. The procedure was performed in the presence and absence of low concentrations of diethylamine, which was expected to prevent low-affinity antigen-antibody binding without affecting the binding of high-affinity antibodies. Anti-BLG IgG antibody affinity also was evaluated in 25 patients with early-stage lung cancer, before and after (5 +/- 1 week) complete surgical excision of the tumor. RESULTS: Results, expressed as the slope of the binding curves and their leftward shift induced by diethylamine, showed different antibody populations between the two groups. Control sera showed a heterogeneous population of anti-BLG IgG antibodies, including antibodies of higher (steeper slope) and lower (more gradual slope) functional affinity. Cancer sera exhibited a less heterogeneous population of anti-BLG IgG antibodies, mostly with lower functional affinity. No change was observed in anti-BLG IgG antibody affinity in the 25 lung cancer patients tested 5 +/- 1 week after complete surgical excision of the tumor. CONCLUSIONS: These results document a persistent qualitative immunologic disturbance in patients with lung cancer, regardless of the type and extent of tumor. The potential relationship between this observation and the development of lung cancer, however, is presently unknown.

Adult↗

PubMed1993

Atopic dermatitis: role of food and house dust mite allergens.

OBJECTIVE: The aim of this study was to evaluate the humoral immune response to cow milk (CM) protein, soya protein, and house dust mites in a group of 64 CM-fed infants, who had atopic dermatitis as the sole atopic manifestation, by measuring not only IgE but also specific IgG antibodies (Ab) against bovine beta-lactoglobulin, soya flour aqueous extracts, and Der P1 antigens. METHODS: A CM-free diet (Nan HA, Nestle) was given to these 64 CM-fed infants and the sensitivity to CM proteins was established by a positive challenge test with the offending food in improved infants. The serum was obtained just before the start of the CM-free diet, at the first consultation. The patients were classified into two groups according to their clinical response to the hypoallergenic formula. RESULTS: Thirty-one infants (group 1) improved dramatically (positive challenge test), and 33 (group 2) did not improve with the exclusion diet but did improve after eviction of dust-producing items in the environment. The two groups were different in terms of their total IgE immunoglobulin concentration (higher in group 1, P < .05) and concentration of specific IgE Ab against CM protein (more frequent in group 1, P < .01). The IgG Ab concentrations against beta-lactoglobulin, the major CM antigen (P < 10-4), and against soya protein (P < .01) were significantly more elevated in the group improved by the diet, with a threshold above which the response to the exclusion diet could be predicted as positive. On the contrary, the level of specific IgG Ab against house dust mites was four times higher in group 2 than in group 1. Twenty-nine of the 33 infants of group 2 improved after eviction of dust-producing items in the environment. CONCLUSIONS: It is proposed that specific IgG Ab concentrations against beta-lactoglobulin, soya protein, and Der P1 antigen be determined in infants and children suffering from atopic dermatitis as a means of predicting the response to an exclusion diet, and a possible role of house dust mites in the pathogenicity of the disease is suggested.

Animals↗

PubMed1992

Abnormal humoral immune response to mucosal antigenic stimulation in patients with lung cancer.

Previous studies have suggested an inverse relationship between atopy and cancer of mucosal surfaces. Atopy is classically assessed by detecting specific immunoglobulin E (IgE) antibodies against inhalant allergens. However, Platts-Mills recently proposed that atopy is the ability of an organism to recognize and to respond to limited doses of allergens presented at the mucosal level by producing not only IgE, but also immunoglobulin A and immunoglobulin G (IgG) antibodies. The authors compared the prevalence of atopy in 103 patients with lung cancer (a model of mucosal cancer), 51 patients with chronic obstructive pulmonary disease matched for age, sex, and smoking habits with patients with lung cancer, and 102 healthy control subjects. The authors investigated whether the IgG response to antigens presented at the mucosal level, exacerbated in atopic subjects, might inversely be decreased in patients with lung cancer. Serum IgE antibodies against five common inhalant allergens (Dermatophagoides pteronyssinus [Der p1], Aspergillus fumigatus, grass pollen, and cat and dog danders) were detected through a radioallergosorbent test assay. Serum IgG antibodies against allergens naturally presented at the mucosal level (respiratory mucosa with Der p1 and digestive mucosa with betalactoglobulin [BLG] and soya proteins [SP]) were measured through a solid phase enzyme-linked immunosorbent assay test. Atopic status was assessed in 19 patients (18.4%) with lung cancer, 9 patients (17.6%) with chronic obstructive pulmonary disease (COPD), and 18 healthy control subjects (17.6%). Distributions of specific IgG levels were represented on frequency histograms after natural logarithmic transformation and showed reduced levels of anti-Der p1 and anti-BLG IgG in the cancer population compared with the control populations but similar levels of anti-SP IgG. Influence of sex, age, smoking habits, histologic type of cancer, and its extent could be excluded. The authors' results show no difference in the prevalence of atopy between the three groups. They document a selective, rather than general, defect in the immune response initiated at the mucosal level in patients with lung cancer, the most frequent mucosal cancer in man.

Administration, Inhalation↗