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Biomedical subjects

M T Guinnepain

Publications and source records attributed to M T Guinnepain.

At least 19 recordsLinked to original sources

Il-4 and IFN-gamma mRNA induction in human peripheral lymphocytes specific for beta-lactam antibiotics in immediate or delayed hypersensitivity reactions.

Beta-lactam antibiotics elicit CD4+ and CD8+ T-cell-mediated immune responses that play a central role in allergic reactions. However, the involvement of a type 1- (Th1 or Tc1) or a type 2-like (Th2 or Tc2) differentiation in drug allergy remains unclear. We investigated the expression of interleukin 4 (IL-4) and interferon gamma (IFN-gamma) mRNA by quantitative reverse transcription and polymerase chain reaction (RT-PCR) in patient-derived peripheral blood lymphocytes following specific in vitro stimulation. Samples were collected from a total of 19 patients who had developed immediate or delayed clinical manifestations of hypersensitivity to beta-lactam and from 11 control subjects. Peripheral blood mononuclear cells (PBMCs) were stimulated with either free antibiotics or antibiotic-human serum albumin (HSA) conjugates. Specific induction of IFN-gamma mRNA expression was observed in 11 of 11 allergic patients with immediate reactions, in 6 of 8 patients with delayed reactions, and in 4 of 11 control subjects. IL-4 mRNA expression was induced in 5 of 11 allergic individuals with immediate reactions but in none of the 8 patients with delayed responses and none of the 11 control subjects. IL-4 mRNA expression was only induced following activation with free drugs, while IFN-gamma mRNA expression was predominantly induced in CD4+ T cells following stimulation with HSA-conjugated drugs. Immediate-type hypersensitivity to beta-lactams was not associated with a pure type 2-like response when PBMCs were specifically stimulated in vitro: Some patients with well-documented history of beta-lactam-induced immediate allergic reaction showed a high IFN-gamma response. Contact dermatitis involved Tc1 and Th1 cells and other delayed hypersensitivity reactions to beta-lactams were restricted to Th1 responses.

Adolescent↗

Mechanisms of drug-induced allergic contact dermatitis.

Allergic contact dermatitis is induced by a wide variety of drugs that trigger specific immune responses following topical exposure. Identified chemical structures involved in such reactions include the mercuric and thiosalicylic acid groups of thimerosal, the diphenylketone group of the anti-inflammatory drug ketoprofen, the amide or ester structure of local anesthetics, and the side-chain and thiazolidine ring of beta-lactams. The T cell responses to such compounds involve CD4+ and CD8+ alphabeta+ T lymphocytes and also CD4 /CD8 gammadelta+ T cells. Although "T helper 2" cytokine production by drug-specific human T cells from patients with allergic contact dermatitis has been described, T helper 1-like and T cytotoxic 1-like responses clearly play key roles in this cutaneous reaction.

Allergens↗

Sublingual-swallow immunotherapy (SLIT) in patients with asthma due to house-dust mites: a double-blind, placebo-controlled study.

A double-blind, placebo-controlled study was carried out in 85 patients with a well-documented history of perennial asthma caused by house-dust mites. Patients received either placebo or sublingual immunotherapy (SLIT) with a standardized Dermatophagoides pteronyssinus (DP)-D. farinae (DF) 50/50 extract. After a run-in period, patients received increasing doses up to 300 IR every day for 4 weeks and then three times a week for the following 24 months. The cumulative dose was about 104000 IR, equivalent to 4.2 mg Der p 1 and 7.3 mg Der f 1. Symptom and medication scores and respiratory function were assessed throughout the trial. Serum specific IgE and IgG4 were determined before SLIT (t0) and after 6 (t1), 11 (t2), 17 (t3), and 25 months (t4) of SLIT. Mite exposure was evaluated at t0, t2, and t4 by semiquantitative guanine determinations. Patients aged 15 years and older were asked to assess their quality of life (QoL) by completing the SF20 (Short Form Health Status Survey) plus two items at t0, t2, and t4. Use of inhaled corticosteroids and beta2-agonists was significantly decreased after 25 months of treatment in both groups (P<0.03). SLIT patients showed significant improvements in respiratory function at t4 (% predicted FEV1 (P = 0.01), VC (P = 0.002), morning (P = 0.01) and evening (P = 0.03) PEFR), and reduction in daytime asthma score (P = 0.02). In the SLIT group, the post-treatment PD20 was 1.75 times higher than the baseline value. There was no change in PD20 in the placebo group. Compared to the placebo group, the SLIT group showed a significant increase in specific IgE DP(P = 0.05), IgE DF(P = 0.02), IgG4 DP(P = 0.001), and IgG4 DF (P = 0.001) levels after SLIT. QoL scores were similar in both groups at t0 and t2. At t4, all scores were better in the SLIT group than in the placebo group, with the differences being most marked for the general perception of health (P = 0.01) and physical pain (P = 0.02). Adverse events were similar in the two groups. This study shows that SLIT in house-dust-mite-related asthma has a good safety profile and improves respiratory function, bronchial hyperreactivity, and QoL.

Administration, Sublingual↗

Human IgG monoclonal antibodies that modulate the binding of specific IgE to birch pollen Bet v 1.

Birch pollen allergy is a very frequent pathology in Europe and North America. More than 95% of the tree pollen allergic patients display IgE reactivity against Bet v 1, the major birch pollen allergen. Starting with PBL from a patient desensitized by immunotherapy, we have generated five B cell lines (BAB1 to BAB5) that secrete human IgG mAbs of high affinity for Bet v 1. Although competition studies indicated that these human IgG mAb recognized different epitopes, broad cross-reactivity was found with Bet v 1 homologous allergens present in tree pollens and plant-derived foods. When tested for interference with allergic patients' IgE, BAB1 inhibited (by 80-100%) the binding of IgE to nitrocellulose-blotted Bet v 1, while BAB2 enhanced it. The biologic significance of the ability of BAB1 to interfere with patients' IgE binding is indicated by the finding that BAB1 completely inhibited Bet v 1-induced histamine release from allergic patients' basophils. Allergen-specific human IgG mAbs such as BAB1, which presents high blocking activity in both immunochemical and cellular IgE competition experiments, might have therapeutical application.

Adjuvants, Immunologic↗

Exercise-induced anaphylaxis: useful screening of food sensitization.

BACKGROUND AND OBJECTIVES: Exercise-induced anaphylaxis is a well-defined entity as described by Sheffer and Austen. Exercise-induced anaphylaxis can be associated with ingestion of a specific food. We report our experience with a series of cases of exercise-induced anaphylaxis in which anaphylaxis was considered to be associated with food allergy. METHODS: We observed 19 patients in whom severe systemic signs of anaphylaxis occurred during or immediately after exercise, while the severity of reactions excluded challenge testing. The causal relationship with various foods was systematically investigated in all cases, even in the absence of any history of allergy. RESULTS: Sensitization to wheat flour was demonstrated in 12 patients, to peanut in seven, and to tree nuts in six cases with skin tests and/or RAST. Sensitivity to various other foods was found less often. Further, avoidance of specific foods according to results of skin tests and RAST was systematically observed during the five hours prior to exercise and no symptom occurred, suggesting a role of specific food intake in the pathogenesis of exercise-induced anaphylaxis. With such elimination diets, most of these young patients were able to engage in regular vigorous exercises (more than twice a week in some cases) without any clinical manifestation with a median followup of 2 years. In two patients, however, recurrence of exercise-induced anaphylaxis was subsequently explained by concomitant ingestion of other foods such as rice and peanut. Additional avoidance of these foods before exercise was then effective in 14 cases (median follow up: 2 years). CONCLUSIONS: Investigations to detect food sensitization, in particular to wheat, peanut and/or tree nuts, and specific avoidance of these foods five hours before exercise appear essential in cases of exercise-induced anaphylaxis.

Adolescent↗

Human auto-anti-idiotypic antibodies to mite-specific IgE can degranulate human basophils in vitro.

BACKGROUND: Anti-idiotypic antibodies (anti-Ids) to specific IgE antibodies are formed spontaneously during an anti-allergen immune response and can be induced by immunotherapy. Although anti-Ids can down-regulate the production of IgE antibodies, at least in experimental models, their possible role in the modulation of target cell reactivity remains ill-defined. OBJECTIVE: The capacity of human anti-Ids to modulate the release of histamine was examined in an in vitro system of human basophil degranulation. Anti-Ids were prepared from the serum of six Dermatophagoides pteronyssinus (Dp)-hypersensitive patients suffering from atopic dermatitis and who had never been desensitized. Basophils were obtained from the blood of atopic donors. The extent of histamine release was determined using a fluorometric assay. RESULTS: We show that: anti-Ids trigger the release of histamine in an allergen-specific, dose- and IgE-dependent manner; the release is not due to the presence of allergen and/or anti-IgE antibodies; and that the degranulating activity can be removed by absorption with affinity-purified anti-Dp antibodies of the corresponding patient. CONCLUSION: These results indicate that spontaneously produced human anti-Ids can modulate the reactivity of human basophils.

Allergens↗

Seasonal increase of spontaneous histamine release in washed leucocytes from rhinitis patients sensitive to grass pollen.

The spontaneous histamine release (SHR) in basophils from patients sensitive to grass pollen has been studied before and during the 1987 grass pollen season. Nineteen patients were recruited on seasonal rhinitis symptoms, positivity for cutaneous tests and for serum-specific IgE with grass pollen. At the time of the biological investigations the patients were following a clinical trial of hyposensitization, including placebo, calcium phosphate and aluminium hydroxide-adsorbed grass pollen extract treatments. During the pollen season, grass pollen counts and clinical scores were checked over a 40-day period. Mean SHR was significantly higher during the pollen period than before, for the whole population of 19 patients (10.9% and 4.6%; P less than 0.005) as well as when the high SHR responders were excluded (5.5% and 3.6%; P less than 0.01). No significant correlation existed between SHR and clinical scores or treatments. SHR could be inhibited at 4 degrees C, in absence of CA++ or of oxidative metabolism and thus originated from cells actively secreting histamine.

Adolescent↗

Comparison of conidial and mycelial allergens of Alternaria alternata.

Alternaria allergens, separated by SDS polyacrylamide gel electrophoresis and transferred onto a nitrocellulose membrane, were identified using sera from Alternaria-allergic patients. 30 Alternaria components of spore and mycelium, ranging in molecular weight from more than 150 to 12 kD, bound IgE antibodies. 15 were detected by more than 25% of the sera and only 4 (85, 56, 42, 31 kD) by more than 50% of the sera. Among these four major allergens, the 56-kD component was present mostly in the spore extract, the 85- and 42-kD fractions in the mycelium extract and the 31-kD in both extracts. The 31-kD component showed the highest IgE binding and the highest frequency of binding (95% with mycelium extract and 79% with spore extract). It was composed of two subunits.

Allergens↗

Lymphocyte proliferative responses to the purified Dermatophagoides farinae major allergen in untreated and hyposensitized atopic patients.

We investigated the proliferative response of lymphocytes from mite-sensitive patients (RAST D.far greater than 3.5 PRU/ml) in the presence of the major allergen Der.f.I purified from Dermatophagoides farinae. Comparative studies were carried out with peripheral blood mononuclear cells from non-atopic donors (RAST = 0), and from patients undergoing hyposensitization treatment (5 to 24 months). According to Student's t-test, there was no significant difference in the Der.f.I-induced proliferation of peripheral blood mononuclear cells from normal donors, untreated atopic patients and hyposensitized patients. In conclusion, it was impossible to discriminate between normal donors, atopic patients and hyposensitized patients with regard to their circulating lymphocyte responses to the purified major allergen Der.f.I.

Allergens↗

[Treatment of chronic urticaria with astemizole: a multicenter pediatric study].

An open multicentric pediatric clinical trial has been performed to evaluate the safety and efficacy of astemizole (HISMANAL suspension) at a 1 ml (2 mg) dosage per 10 kg body weight once daily in children with chronic urticaria. A good and very good effect has been observed in 63.2% of the children at day 7, in 79.2% after 2 weeks and in 88.9% at the end of the treatment (4 weeks). A marked improvement of the symptoms was reported in 63.8% of children at day 7. There was no decrease of efficacy at the end of the treatment. Tolerance was good in 87.% of the cases. Astemizole seems to be a useful treatment for chronic urticaria in pediatrics.

Adolescent↗

[Seasonal changes in specific IgE: the acarid Dermatophagoides pteronyssinus].

The authors have studied monthly the titres of specific IgE to Dermatophagoides pteronyssinus, by Phadebas RAST, in 8435 measurements, spread over 4 years. Significant seasonal and monthly variations were seen every year with a maximum level in the autumn or the beginning of winter, with a second peak at the end of winter in 3 years of the 4. There was no close superposition of pattern form one year to another. The domestic relative humidity had a significant effect on the seasonal variation with a mean shift of 2 months that could be explained by the length of the biological cycle of the mites. These data compare with those of the literature (sampling of mites in bedding, longitudinal studies...).

Acari↗

[Preventive treatment of severe allergic complications caused by Hymenoptera venom. Our experience apropos of 250 cases].

Out of a total of 350 referrals for allergy to hymenoptera venom over four years, 250 patients who had one or more severe systemic reactions were selected for a "rush course" of immunotherapy after confirmation of the responsible reagin (skin tests, specific IgE). The method used in the 245 patients who accepted the protocol enabled us to arrive at a maintenance dose of 100 micrograms of venom in three days. Tolerance was excellent; no serious side effects were observed; the course of immunotherapy did not have to be stopped in any of the patients. Clinical efficacy appeared to be satisfactory as no systemic reaction occurred in a fifth (50) of the patients treated who were bitten again, either spontaneously (24 cases), sometimes successfully and repeatedly (11 cases), or intentionally (26 cases). The IgG antivenom antibody was constantly raised from the first month and remained at a stable value. This harmless and effective method should be offered to patients allergic to hymenoptera venom.

Adolescent↗

Rush venom immunotherapy: a 3-day programme for hymenoptera sting allergy.

In a series of 102 patients consulting for allergic reactions following hymenoptera sting, fifty-two of them, who had experienced one or more severe systemic adverse reactions were selected for rush immunotherapy. The method employed made it possible to attain the maintenance dose of 100 micrograms of venom in 3 days. Patient tolerance was excellent, no serious side-effect was observed; immunotherapy never had to be stopped. Clinical effectiveness seems to be very satisfactory, since no abnormal reaction was reported in seven patients who later were spontaneously stung, and in fourteen patients who received an induced insect sting. The level of IgG antivenom antibodies rose regularly from the first month onwards to remain at a stable level. Because of its safety and effectiveness, it appears that this method should be recommended for immunotherapy in patients who are allergic to hymenoptera stings.

Adolescent↗