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922 A clinically relevant model for evaluation of DNA-based therapy for allergy
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Abstracts
Immunotherapy Units: A Follow Up Study After 15 Months of Evolution Immaculada Sdnche: Machin*. JosC Carlos Garcia Robaina*. E Ferncindez-Caldasf, Carmen Banner*. Carmu de Blase, Mercedes Sdnchez Triviiio*, Fernando de la Terre Morfn* *Hospital Nuestra Seiiora de la Candelaria, Tenerife, Canary Islands, Spain tCBF LETI, SA Research Laboratories, Madrid, Spain Immunotherapy units are becoming an increasingly important component of Allergy and Immunology Departments in Spain. The objective of this study was to establish the rate of adverse reactions registered in an immunotherapy unit in the Canary Islands, Spain from May of 1998 to July of 1999. A total of 3,214 immunotherapy doses were administered to 287 patients (101 males, and 186 females, 4 of whom were pregnant). Two hundred twenty-one patients (73.2%) were receiving mite; 38 patients (12.5%) pollen; 7 patients (2.4%) cat; 2 patients (0.6%) Altemaria and 34 patients (11.3%) hymenoptera venom altemata, immunotherapy. Two hundred seventeen patients (72.3%) had rhinoconjunctivitis and asthma; 44 (14.6%) rhinoconjunctivitis, 5 (1.7%) asthma and 34 (11.3%) hymenoptera sensitivity. A total of 40 episodes of adverse reactions were recorded (1.2% of all the administered doses). Thirty of these reactions (75%) occurred within 30 minutes after the injection was administered, consisting of 11 large local reactions (0.3% of all the injections given) and 19 systemic reactions (0.5%). which occurred only in asthmatic patients. All the systemic reactions were mild and rapidly reversible with the appropriate treatment. Only in 2 cases, an immediate systemic reaction was associated with a large local reaction. Ten reactions (25%) occurred after 30 minutes and consisted only of large local reactions. Thirteen systemic episodes (68% of all the systemic reactions) were registered at initial build-up doses. Regarding the types of allergens, 2 individuals with cat epithelium: 3 with pollen, 13 with mites and 1 with hymenoptera venom immunotherapy experienced a systemic reaction. Only 1.2% of the administered doses presented any kind of adverse reaction, of which only 0.5% were systemic. These systemic reactions were always mild and rapidly reversible with the adequate treatment and there was no vital danger for any patient. Immunotherapy is a safe modality of treatment for allergic respiratory diseases. A Clinically Relevant Model for Evaluation of DNA-Based Therapy for Allergy E Duarte. L Luo. G Silverman University of California. San Diego To develop DNA-based therapies that ameliorate the pathologic responses relevant to a common allergic state, we are developing a small animal model of allergy using the common house dust mite, Dermatophagoides. Toward this goal, we have independently cloned and expressed in bacterial and mammalian systems dominant allergenic proteins, including Der pteronyssinus II (Der p II). We have found that immunization with recombinant Der pl1 protein without adjuvant, or subcutaneous injection of the naked expression plasmid encoding for Der p II, induces an antibody response that recognizes conformational B-cell epitopes in the native dust mite protein. In preliminary studies, we have characterized the immune response to exposure to Der p II in different immune contexts. As expected, mice immunized with the recombinant protein in saline showed both IgGl and IgG2a responses, while all mice immunized with the Der p II in alum exhibited a strong IgGl and IgE response. Notably, immunization with the Der p II gene vaccination vector
J ALLERGY CLIN IMMUNOL JANUARY 2000
induced a response involving only IgGl and no detectable IgG2a or IgE. Importantly. mice immunized with Der p II plasmid DNA and boosted with Der p II in alum induced both an IgG I and IgG2a antibody response. In addition, mice immunized with Der p II in alum and then boosted with Der P II plasmid DNA, showed an IgGl response without IgG2a or IgE. In preliminary in vitro stimulation cytokine profile studies. we found splenocytes from mice treated with Der p 11 in alum produced the expected response of high IL-5 and lower IFN-g production. In contrast, Der p II gene vaccination elicited both IL-5 and IFN- g, further supporting the notion that Der p II has an inherent propensity to elicit a strong Th2 response. We are currently extending these studies and also evaluating Der p IIspecific IgE responses. We are also studying the relative efficacy of different DNA based approaches for subverting an ongoing Th2biased response, with the goal of developing efficacious and practical therapeutic approaches. 923
Local Reactions During Allergen Immunotherapy Do Not Require Dose-Adjustment MS Tankersley, KA Burler; WK B&es DW Goes Wilford Hall Medical Center, San Antonio, TX BACKGROUND: The recent World Health Organization (WHO) position paper on allergen immunotherapy states that local reactions to immunotherapy are not predictive of subsequent systemic reactions. Nevertheless, in clinical practice dose-adjustment after local reactions continues to be recommended. presumably in an effort to prevent future systemic reactions. OBJECTIVE: To determine whether dose-adjustment versus no-adjustment for local reactions during allergen immunotherapy influences the occurrence of subsequent systemic reaction rates. METHODS: In a single-site allergy clinic prior to October I, 1997, local reactions following allergen immunotherapy injection resulted in adjustment of the subsequent dose. After October I, 1997. no dose adjustments were made for immediate and late local reactions. For the same 9 month period before and after the change in local reaction dose-adjustment policy. systemic reaction rates were compared retrospectively. For individuals experiencing a systemic reaction, local reaction rates and local reactions immediately preceding a systemic reaction were compared before and after the policy change. RESULTS: Comparing the 9 month period (October 96-June 97) preceding the policy change and the 9 months (October 97-June 98) following the change in policy, the systemic reaction rates (0.80% and 1.01%) were not statistically different (P = 0.24). Among those experiencing a systemic reaction, the rate of local reactions was unchanged (7.3% and 4.7%. P = 0.07) and the rate of local reactions immediately preceding a systemic reaction did not increase (18.8% and 10.5%, P = 0.37). The sensitivity of a local reaction predicting a systemic reaction at the next immunotherapy dose was 15%. CONCLUSIONS: A local reaction is a very insensitive predictor for a subsequent systemic reaction at the next immunotherapy dose. Dose-adjustment for most local reactions is unnecessary and may delay therapy, increase costs, and put the patient at increased risk of dose administration errors.
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Immunotherapy Units: A Follow Up Study After 15 Months of Evolution Immaculada Sdnche: Machin*. JosC Carlos Garcia Robaina*. E Ferncindez-Caldasf, Carmen Banner*. Carmu de Blase, Mercedes Sdnchez Triviiio*, Fernando de la Terre Morfn* *Hospital Nuestra Seiiora de la Candelaria, Tenerife, Canary Islands, Spain tCBF LETI, SA Research Laboratories, Madrid, Spain Immunotherapy units are becoming an increasingly important component of Allergy and Immunology Departments in Spain. The objective of this study was to establish the rate of adverse reactions registered in an immunotherapy unit in the Canary Islands, Spain from May of 1998 to July of 1999. A total of 3,214 immunotherapy doses were administered to 287 patients (101 males, and 186 females, 4 of whom were pregnant). Two hundred twenty-one patients (73.2%) were receiving mite; 38 patients (12.5%) pollen; 7 patients (2.4%) cat; 2 patients (0.6%) Altemaria and 34 patients (11.3%) hymenoptera venom altemata, immunotherapy. Two hundred seventeen patients (72.3%) had rhinoconjunctivitis and asthma; 44 (14.6%) rhinoconjunctivitis, 5 (1.7%) asthma and 34 (11.3%) hymenoptera sensitivity. A total of 40 episodes of adverse reactions were recorded (1.2% of all the administered doses). Thirty of these reactions (75%) occurred within 30 minutes after the injection was administered, consisting of 11 large local reactions (0.3% of all the injections given) and 19 systemic reactions (0.5%). which occurred only in asthmatic patients. All the systemic reactions were mild and rapidly reversible with the appropriate treatment. Only in 2 cases, an immediate systemic reaction was associated with a large local reaction. Ten reactions (25%) occurred after 30 minutes and consisted only of large local reactions. Thirteen systemic episodes (68% of all the systemic reactions) were registered at initial build-up doses. Regarding the types of allergens, 2 individuals with cat epithelium: 3 with pollen, 13 with mites and 1 with hymenoptera venom immunotherapy experienced a systemic reaction. Only 1.2% of the administered doses presented any kind of adverse reaction, of which only 0.5% were systemic. These systemic reactions were always mild and rapidly reversible with the adequate treatment and there was no vital danger for any patient. Immunotherapy is a safe modality of treatment for allergic respiratory diseases. A Clinically Relevant Model for Evaluation of DNA-Based Therapy for Allergy E Duarte. L Luo. G Silverman University of California. San Diego To develop DNA-based therapies that ameliorate the pathologic responses relevant to a common allergic state, we are developing a small animal model of allergy using the common house dust mite, Dermatophagoides. Toward this goal, we have independently cloned and expressed in bacterial and mammalian systems dominant allergenic proteins, including Der pteronyssinus II (Der p II). We have found that immunization with recombinant Der pl1 protein without adjuvant, or subcutaneous injection of the naked expression plasmid encoding for Der p II, induces an antibody response that recognizes conformational B-cell epitopes in the native dust mite protein. In preliminary studies, we have characterized the immune response to exposure to Der p II in different immune contexts. As expected, mice immunized with the recombinant protein in saline showed both IgGl and IgG2a responses, while all mice immunized with the Der p II in alum exhibited a strong IgGl and IgE response. Notably, immunization with the Der p II gene vaccination vector
J ALLERGY CLIN IMMUNOL JANUARY 2000
induced a response involving only IgGl and no detectable IgG2a or IgE. Importantly. mice immunized with Der p II plasmid DNA and boosted with Der p II in alum induced both an IgG I and IgG2a antibody response. In addition, mice immunized with Der p II in alum and then boosted with Der P II plasmid DNA, showed an IgGl response without IgG2a or IgE. In preliminary in vitro stimulation cytokine profile studies. we found splenocytes from mice treated with Der p 11 in alum produced the expected response of high IL-5 and lower IFN-g production. In contrast, Der p II gene vaccination elicited both IL-5 and IFN- g, further supporting the notion that Der p II has an inherent propensity to elicit a strong Th2 response. We are currently extending these studies and also evaluating Der p IIspecific IgE responses. We are also studying the relative efficacy of different DNA based approaches for subverting an ongoing Th2biased response, with the goal of developing efficacious and practical therapeutic approaches. 923
Local Reactions During Allergen Immunotherapy Do Not Require Dose-Adjustment MS Tankersley, KA Burler; WK B&es DW Goes Wilford Hall Medical Center, San Antonio, TX BACKGROUND: The recent World Health Organization (WHO) position paper on allergen immunotherapy states that local reactions to immunotherapy are not predictive of subsequent systemic reactions. Nevertheless, in clinical practice dose-adjustment after local reactions continues to be recommended. presumably in an effort to prevent future systemic reactions. OBJECTIVE: To determine whether dose-adjustment versus no-adjustment for local reactions during allergen immunotherapy influences the occurrence of subsequent systemic reaction rates. METHODS: In a single-site allergy clinic prior to October I, 1997, local reactions following allergen immunotherapy injection resulted in adjustment of the subsequent dose. After October I, 1997. no dose adjustments were made for immediate and late local reactions. For the same 9 month period before and after the change in local reaction dose-adjustment policy. systemic reaction rates were compared retrospectively. For individuals experiencing a systemic reaction, local reaction rates and local reactions immediately preceding a systemic reaction were compared before and after the policy change. RESULTS: Comparing the 9 month period (October 96-June 97) preceding the policy change and the 9 months (October 97-June 98) following the change in policy, the systemic reaction rates (0.80% and 1.01%) were not statistically different (P = 0.24). Among those experiencing a systemic reaction, the rate of local reactions was unchanged (7.3% and 4.7%. P = 0.07) and the rate of local reactions immediately preceding a systemic reaction did not increase (18.8% and 10.5%, P = 0.37). The sensitivity of a local reaction predicting a systemic reaction at the next immunotherapy dose was 15%. CONCLUSIONS: A local reaction is a very insensitive predictor for a subsequent systemic reaction at the next immunotherapy dose. Dose-adjustment for most local reactions is unnecessary and may delay therapy, increase costs, and put the patient at increased risk of dose administration errors.