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Biomedical subjects

J M Saint-Remy

Publications and source records attributed to J M Saint-Remy.

At least 55 records · Page 3Linked to original sources
PubMed1993

Anti-factor VIII antibodies of hemophiliac patients are frequently directed towards nonfunctional determinants and do not exhibit isotypic restriction.

A significant proportion of hemophilia A patients receiving transfusions of factor VIII (FVIII) develop a specific antibody response towards FVIII. These antibodies are usually detected by assays in which they inhibit the function of the molecule, such as the Bethesda clotting test. We have prepared anti-FVIII antibodies by specific immunoadsorption from the plasma of four hemophiliacs with stable inhibitor levels. The isotypic distribution of such antibodies was determined and their capacity to bind to insolubilized FVIII was compared with their inhibitory activity in two functional assays, namely, the Bethesda assay and a chromogenic assay. In addition, the FVIII epitope specificity was determined by competition with monoclonal antibodies for the binding to insolubilized FVIII. We show here that (1) anti-FVIII antibodies are not isotypically restricted; thus, a significant proportion of specific IgG2 was found; (2) antibodies are frequently directed towards epitopes of FVIII that are not directly involved in the function of the molecule and therefore escape detection in the Bethesda method or chromogenic assay; and (3) each patient shows a unique pattern of FVIII epitope recognition. We conclude that evaluation of anti-FVIII antibodies by a functional method does not provide an accurate evaluation of the specific antibody response. These findings have important implications for the comparison of the immunogenicity of FVIII molecules produced by different technologies and for the development of methods to control anti-FVIII antibody production.

Adolescent↗
PubMed1993

A higher than expected incidence of factor VIII inhibitors in multitransfused haemophilia A patients treated with an intermediate purity pasteurized factor VIII concentrate.

In May 1990, 218 patients with haemophilia A regularly attending the Leuven Haemophilia Center were randomly assigned to a group receiving either of two newly introduced factor VIII concentrates: factor VIII-P, an intermediate purity pasteurized concentrate, or factor VIII-SD, a high purity concentrate treated with solvent-detergent for viral inactivation. Patients were followed from May 1990 until October 1991. Between August 1991 and October 1991 a clinically important factor VIII inhibitor was detected in five out of the 109 patients receiving factor VIII-P while none of the 109 patients receiving factor VIII-SD developed such antibodies. All patients acquiring an inhibitor had previously been clinically tolerant to transfused factor VIII with 200 to more than 1,000 days of exposure to factor VIII prior to May 1990. Patients with inhibitors were transfused daily with 30 U factor VIII-SD per kg body weight, which was associated with a gradual decline of the inhibitor level. In all patients the antibodies were relatively slow-acting and predominantly directed towards the light chain of factor VIII. This study demonstrates a higher than expected incidence of factor VIII inhibitors associated with the use of a specific factor VIII concentrate in multitransfused haemophilia A patients. It indicates the usefulness of evaluating newly introduced concentrates in prospective, randomized trials.

Adolescent↗
PubMed1993

A novel therapy for atopic dermatitis with allergen-antibody complexes: a double-blind, placebo-controlled study.

BACKGROUND: Exposure to airborne allergens exacerbates symptoms of atopic dermatitis (AD) in hypersensitive patients. OBJECTIVE: Our purpose was to determine whether the administration of allergen-antibody complexes would improve the symptoms of AD. METHODS: Twenty-four adults with AD and hypersensitivity to Dermatophagoides pteronyssinus (Dpt) were treated in a double-blind, placebo-controlled trial by intradermal injections of complexes containing autologous specific antibodies and Dpt allergens. After 4 months, placebo-treated patients started receiving active treatment. All patients were treated for a full year. Clinical status and Dpt-specific IgG and IgE antibody levels were monitored. RESULTS: Symptoms of AD subsided within a few weeks after starting therapy, with significant reduction after 4 months in treated patients only. After 1 year, 82% of the patients exhibited a mean improvement of 83%, associated with reduction of Dpt-specific IgG antibodies. CONCLUSION: The treatment of Dpt-sensitive patients with AD by injections of allergen-antibody complexes is safe and effective in a majority of patients.

Adolescent↗
PubMed1993

Significant reduction of nonspecific bronchial reactivity in patients with Dermatophagoides pteronyssinus-sensitive allergic asthma under therapy with allergen-antibody complexes.

Thirty-nine asthmatic patients hypersensitive to Dermatophagoides pteronyssinus were treated for a total of 4 yr with injections of complexes made of allergen and autologous specific antibodies. The results obtained throughout the first 2 yr of a double-blind placebo-controlled trial have been published (1) and we now report the results of such therapy during an additional 2 yr. Three groups of patients had been defined: Groups A and B were comprised of patients treated with either "higher" doses of complexes (Group A) or "lower" doses (Group B), whereas Group C received the placebo preparation. Four injections of complexes were performed during the third yr and none during the fourth yr. The clinical benefit resulting from such injections was maintained until the end of the study, whereas medication intake, especially systemic or high doses of inhaled corticosteroids, was much reduced. Skin reactivity to allergen was significantly decreased in both treated groups. Bronchial provocation tests were carried out at 1-yr intervals with either allergen or acetylcholine (ACh). Reactivity to allergen inhalation was significantly decreased at each time point. Reactivity to ACh was significantly decreased at the end of Years 3 and 4. Fifty percent of treated patients who underwent bronchial challenges lost their bronchial reactivity to the highest concentrations of both allergen and ACh. A significant improvement in the basal lung function was observed in both treated groups. The long-term effects of immunotherapy with allergen-antibody complexes in allergic asthma patients thus include reduction in nonspecific bronchial reactivity.

Allergens↗
PubMed1992

Treatment of atopic dermatitis by allergen-antibody complexes: long-term clinical results and evolution of IgE antibodies.

This study describes the long-term follow-up of the clinical response of 10 adult patients suffering from atopic dermatitis (AD) who were treated by administration of complexes made of Dermatophagoides pteronyssinus (Dpt) allergens and autologous antibodies specific to that allergen. We have already described the clinical improvement observed after 1 year of treatment involving regular injections of complexes; this improvement was maintained throughout a second year, even though the number of injections was greatly reduced. At the end of the second year of treatment, 5 patients were completely free of disease, and 3 had had a short-lasting recurrence of low-severity dermatitis. Using a disease intensity index the mean improvement for these 8 patients was 83% compared to baseline values. One patient showed a significant recurrence of symptoms, and 1 patient left the study for personal reasons when she was in good clinical condition. A significant reduction of specific anti-Dpt IgE antibody titers was observed in 7 out of the 8 patients in clinical remission, while the level of total IgE antibodies was unchanged until the very end of the study. This study not only confirms that clinical benefit can be obtained from the treatment of AD patients hypersensitive to Dpt by injections of allergen-antibody complexes but also indicates that the therapy induces a suppression of IgE antibody production that is specific for the particular allergen.

Allergens↗
PubMed1992

Allergen-antibody complexes in the treatment of atopic dermatitis: preliminary results of a double-blind placebo-controlled study.

Twenty-three adult patients suffering from chronic atopic dermatitis (AD) have been treated by regular injections of complexes made of D. pteronyssinus allergens and specific autologous antibodies. A double-blind placebo-controlled protocol was followed for 4 months, then the patients were treated openly to complete a full year on active therapy. Preliminary results are presented for the first 8 months. Seventy-three percent of patients improved when treated with complexes, showing a mean improvement of more than 70% after 4 months. This study suggests that injections of allergen-antibody complexes is an effective treatment of at least some forms of AD and confirms that airborne allergens are significant exacerbating factors of AD.

Adolescent↗
PubMed1991

Allergen-antibody complexes can efficiently prevent seasonal rhinitis and asthma in grass pollen hypersensitive patients. Allergen-antibody complex immunotherapy.

We have prepared antigen-antibody complexes from grass pollen allergens and autologous specific antibodies isolated by immunoadsorption from the serum of allergic patients. These complexes were inoculated into patients in a double-blind trial to evaluate their effect on grass pollen-related rhinitis and bronchial asthma. Thirty-eight grass pollen-hypersensitive patients were allocated to three groups; patients in the first two groups were treated with antigen-antibody complexes at different ratios and dosages and were compared with the third group who received the placebo carrier buffer alone. In addition, we treated a fourth group who had already received antigen-antibody complex inoculation during the previous pollen season. Injections were given every 2 weeks during the pollen season, starting 5 weeks prior to it. Tolerance was excellent with no signs of local or systemic side effects. The treatment prevented nasal symptoms while enabling the patients to reduce antihistamine intake. Bronchial asthma was virtually absent in the treated groups even though no bronchodilators or corticosteroids had to be taken. Specific IgE antibodies did not increase during the pollen season nor did IgG "blocking" antibodies. Inoculation of allergen-antibody complexes could provide a valuable alternative for the treatment of immediate hypersensitivity to airborne allergens as it appears to be safe and rapidly efficacious. This treatment offers several advantages compared to conventional hyposensitization and is characterized by the absence of an increase in specific IgG antibodies.

Adolescent↗
PubMed1991

Injection of allergen-antibody complexes is an effective treatment of atopic dermatitis.

Atopic dermatitis (AD) can be exacerbated by contact with airborne allergens, amongst which Dermatophagoides pteronyssinus (Dpt) appears to be potentially important. Specific IgE antibodies towards Dpt are often found in AD, and it can therefore be speculated that suppression of the production of anti-Dpt IgE might result in a significant clinical improvement. Complexes of antigen and specific antibodies have been shown to suppress the production of antibody in other systems; we report here the evaluation in an open trial of the capacity of such complexes to improve symptoms of AD. Ten adult patients were enrolled in this study. In addition to satisfying the criteria of AD, they all suffered from a severe disease (more than 20% of the body surface involved) that had been stable for at least the last 2 years. The patients had high titers of total IgE antibodies and specific anti-Dpt antibodies. Allergen-antibody complexes were prepared from Dpt allergens and an excess of autologous specific anti-Dpt antibodies obtained by immunoadsorption. The patients received regular injections of these complexes throughout 1 year, during which clinical parameters of disease intensity, percentage of body surface affected and intensity of pruritus were regularly monitored. A significant clinical improvement was obtained after 3-4 months of therapy and was maintained through the 9th month. After 1 year of treatment, 2 patients were completely free of disease, 4 had residual lesions which continued to improve and 4 patients had a partial recurrence of dermatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Complexes of grass pollen allergens and specific antibodies reduce allergic symptoms and inhibit the seasonal increase of IgE antibody.

Complexes made from antigen and specific antibodies have been used to suppress specific antibody production. This property is of potential therapeutic interest in immediate hypersensitivity states which are characterized by hyperproduction of IgE antibodies. We report here on the use of antigen-antibody complexes in patients with hypersensitivity to grass pollen. Specific anti-allergen antibodies were prepared by immunoadsorption from the serum of hypersensitive individuals and mixed with grass pollen allergens to form complexes in antibody excess. These complexes were used in a strictly autologous manner for inoculating patients prior to and during a pollen season. The study comprised two randomly defined groups of 15 patients who were inoculated intradermally either with a preparation of allergen-antibody complexes or with the carrier buffer, according to a double-blind protocol. Diary cards were used to follow nasal and ocular symptoms, bronchial asthma and medication intake. Specific IgE antibodies were assayed during the trial and 1 year afterwards. Inoculation of allergen-autologous antibody complexes was well tolerated. It significantly reduced ocular symptoms (Mann-Whitney U-test, P less than 0.05), bronchial asthma during the first part of the season (Mann-Whitney U-test, P less than 0.001) and drug intake (Mann-Whitney U-test, P less than 0.001). This treatment prevented the seasonal increase in specific IgE antibodies, whose production continued to decrease after the pollen season. These effects were obtained within a few weeks of treatment, using a cumulative amount of allergen 100-fold lower than the amount which would have been used for a conventional hyposensitization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Allergic bronchial asthma due to Dermatophagoides pteronyssinus hypersensitivity can be efficiently treated by inoculation of allergen-antibody complexes.

Antigen-antibody complexes were made from allergens of the common house dust mite, Dermatophagoides pteronyssinus (Dpt) and an excess of purified autologous specific antibodies. These complexes have been used to treat Dpt-hypersensitive patients who suffered from chronic bronchial asthma. Clinical symptoms and medication intake were followed by filling in diary cards. Peak expiratory flow, measured four times a day, was also followed. Intradermal skin tests and bronchial challenge tests were performed with allergen together with an evaluation of nonspecific bronchial reactivity. Specific IgE and IgG antibodies were assayed after separation from the bulk of serum immunoglobulins by immunoadsorption. The study was carried out over two years according to a double-blind protocol. Intradermal inoculation of antigen-antibody complexes resulted in a marked reduction of both clinical and medication scores. No systemic side-effects were observed and only mild wheal and flare reactions were noted at the injection site. The treatment showed a drastic reduction of specific skin and bronchial reactivities with only marginal effects on nonspecific bronchial reactivity. Concentrations of specific IgE antibodies decreased significantly during the first weeks of treatment and remained at these lower values throughout the study. Specific IgG antibodies actually decreased in the majority of treated patients. The total amount of allergen used in this study was less than 1% of the amount currently used for conventional hyposensitization with the same allergen. These findings show that antigen-antibody complex inoculation is an efficient and safe means of treating allergic bronchial asthma and that the mechanism of action is likely to differ from conventional hyposensitization.

Adolescent↗
PubMed1989

Seasonal variation in specific IgE antibodies of grass-pollen hypersensitive patients depends on the steady state IgE concentration and is not related to clinical symptoms.

To evaluate parameters that determine the serum titer of specific antiallergen IgE antibodies, we graded the clinical symptoms of 78 grass-pollen hypersensitive patients during two consecutive seasons, while serum total and specific antigrass-pollen IgE antibodies were titrated every 2 weeks. Correlation studies of clinical symptoms, grass-pollen counts, and specific IgE antibodies demonstrated that (1) bronchial asthma and nasal symptoms cannot be predicted on the basis of preseasonal IgE titers, (2) clinical symptoms are not related to seasonal antigrass-pollen IgE antibodies, (3) antigrass pollen and total IgE antibodies are not directly dependent on the air pollen point concentration, (4) increase in specific IgE antibodies during the pollen season is strongly correlated to preseasonal specific IgE titers, and (5) individual fluctuations of specific IgE antibody titers during the pollen season are proportional to preseasonal specific IgE titers. These findings suggest that titration of serum-specific IgE antibodies is of little use in predicting or monitoring the clinical symptoms of grass-pollen hypersensitive patients, since IgE titers strongly depend on individual immune responsiveness.

Adolescent↗
PubMed1988

Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinus. III. Cross-reactivity of bystander idiotopes on allergen-specific IgE antibodies.

Rabbits were inoculated with affinity-purified human antibodies to the common house dust mite Dermatophagoides pteronyssinus (DPT) to produce anti-idiotypic (Id) antibodies. The Id carried by human IgE antibodies were studied in a radioimmunoassay in which specific anti-DPT IgE were first insolubilized on rabbit F(ab')2 fragments against human Fc epsilon. In a single individual specific anti-DPT IgE antibodies shared bystander idiotopes (i.e. idiotopes located outside the antigen-binding site) with IgG antibodies of the same specificity, since the adsorption on insolubilized anti-DPT IgG almost completely eliminated the binding of anti-Id antibodies to IgE. This differed from our previous observations (J.-M. R. Saint-Remy et al., Eur. J. Immunol. 1986. 16: 575) wherein distinct paratope-associated idiotopes were identified on IgG and IgE anti-DPT antibodies. The frequency of cross-reactions between idiotopes of anti-DPT IgE antibodies observed in ten unrelated individuals was less than 10% for bystander idiotopes. This finding confirmed the private character of the above idiotopes that we found earlier on anti-DPT IgG antibodies. However, one anti-Id antibody preparation was found to react with bystander idiotopes of anti-DPT IgE of most individuals, thereby suggesting the existence of a recurrent idiotope. The low frequency of inter-individual bystander idiotope cross-reactivity contrasted with the public character of paratope-associated idiotopes.

Allergens↗
PubMed1988

Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinus. IV. Occurrence of natural autologous anti-idiotypic antibodies.

IgG isolated from the plasma of seven individuals hypersensitive to the common house dust mite Dermatophagoides pteronyssinus (DPT) was exhaustively adsorbed onto insolubilized DPT. The unbound fraction was found by radioimmunoassay to contain antibodies recognizing the variable region of both anti-DPT IgG and IgE antibodies. This recognition was idiotype (Id)-specific as it persisted after passage over insolubilized polyclonal IgG of unrelated specificity. Most of these anti-Id IgG carried the internal image of the initial antigen in that they competitively inhibited the binding of anti-DPT antibodies to DPT. Immunoadsorption of anti-Id IgG onto insolubilized anti-DPT IgG antibodies from the same individual completely eliminated their reaction with anti-DPT IgG but not with anti-DPT IgE, suggesting that idiotopes included in the antigen-binding site of specific IgG and IgE antibodies were not identical. Anti-Id IgG recognizing idiotopes located outside the antigen-binding site (bystander idiotopes) were also completely removed by passage over insolubilized anti-DPT IgG; in this case the reaction of the anti-Id IgG with both anti-DPT IgG and anti-DPT IgE was inhibited, indicating that, for a given individual, bystander idiotopes were shared between anti-DPT antibodies pertaining to these two isotypes.

Allergens↗