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Reproducibility of Missing doses as a Predictor of Poor Medication Adherence in Patients Receiving Specific Immunotherapy
S278 Abstracts
Immunoregulatory Effects of Saccharomyces (S.) cerevisiae Mannan via Th2/Th3 Polarization in Mice J. M. Lehman, M. R. Streck, A. S. Tyagi, D. B. Lew; Pediatrics, University of Tennessee Health Science Center, Memphis, TN. RATIONALE: Lipoglycans from mycobacteria have been shown to stimulate IL-10-producing cells. Lipid modification of mannan causes multimeric engagement of mannose receptors and confers different biological effects. Mannan (Man9Gln) is the major component of the negatively charged outer wall of S. cerevisiae. Mannan from S. cerevisiae inhibits airway hyperreactivity in mice. Studies were conducted to investigate the effects of S. cerevisiae mannan on cytokine production in mice. METHODS: Naive FVB/N and Balb/c mice were given S. cerevisiae mannan (1 - 4 mg, 35-280 mg/kg) or vehicle via intranasally (i.n.) or gavage feeding (p.o.). After 18 hours the mice were sacrificed and superficial cervical lymph nodes (CLNs) and spleens were harvested. Whole CLNs and single cell suspensions of splenocytes were cultured for 72 hours with S. cerevisiae mannan (1mg/ml or saline). Cytokines were determined from the culture supernatants by Quantikine assay. The endotoxin levels of S. cerevisiae mannan were less than 2 EU/ml, measured by the Limulus assay. There were no detectable phospholipids by thin layer chromatography. RESULTS: IL-10 and TGFbeta production was increased two-fold in CLN- and splenocyte-cultures from both strains of mannan-treated mice (1mg, i.n.) compared to controls. Gavage feeding (0 - 4 mg) induced similar trends. There was a dose-dependent increase in IL-10 (30 - 90 pg/ml), IL-5 (70 - 250 pg/ml) and TGFbeta (2 - 4 ng/ml) (n = 4). No significant production of TNFalpha, IFNgamma, IL-4 or IL-12 was detected. CONCLUSIONS: A single dose of phospholipid-free mannan from S. cerevisiae, when given i.n. or p.o., renders systemic Th2/Th3 polarization in mice. Funding: LeBonheur, NIH, AAAAI
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Immunologic Changes after Long-Term Immunotherapy with Hop Japanese Pollen Extracts S. Lee1, S. Kim2, Y. Ye2, S. Kim3, S. Kim2, D. Nahm2, H. Park2; 1Internal Medicine, Dong-A University, Busan, REPUBLIC OF KOREA, 2Allergy and Rheumatology, Ajou University, Suwon, REPUBLIC OF KOREA, 3Internal Medicine, Seoul National University, Seoul, REPUBLIC OF KOREA. RATIONALE: Hop Japanese (Hop J) pollen has been considered as one of the major causative pollen allergens in the autumn season. We developed a new Hop J immunotherapy extract in collaboration with Allergopharma(Reinbeck, Germany) and investigated immunologic mechanisms during 3 yrs’ immunotherapy. METHODS: Twenty patients (13 asthma, 7 rhinitis) were enrolled from Ajou University Hospital. Sera were collected before, 1 yr, and 3 yrs after the immunotherapy. Changes of serum specific IgE, IgG1, and IgG4 levels to Hop J were monitored by ELISA. To evaluate cellular mechanisms, serum IL-10, IL-12, TGF1 and soluble CD23 levels were measured by ELISA. RESULTS: Specific IgG1 increased at 1 yr then decreased again at 3 yrs, and specific IgG4 levels increased continuously (p<0.05, respectively), whereas total and specific IgE levels showed variable responses with no statistical significance. IL-10, IL-12 TGF1 and soluble CD23 level significantly decreased during 3 yrs’ study period. (p<0.05 respectively). CONCLUSIONS: These findings suggest favorable effect of Hop J immunotherapy may be explained by IL-12 and TGF1 mediated immunomodulation and generation of blocking antibodies. This study was supported by a grant of the Korean Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (no. A050571) Funding: Ministry of Health & Welfare, Republic of Korea
1073
J ALLERGY CLIN IMMUNOL FEBRUARY 2006
Induction of Rabbit Specific IgG against Der p 1 and Der p 2 after Immunization with an Allergoid of Dermatophagoides Pteronyssinus E. Fernández-Caldas, M. Gallego, J. Carnés, M. Casanovas, V. Iraola; Laboratorios LETI S.L., Tres Cantos, SPAIN. RATIONALE: Immunotherapy with modified (depigmented and polymerized) extracts of D. pteronyssinus is an effective and safe treatment for allergic asthma and rhinoconjuntivitis. The objective of this study was to demonstrate the induction of specific IgG against Der p 1 and Der p 2 in the sera of rabbits previously immunized with modified extracts of D. pteronyssinus. METHODS: Four New Zealand White rabbits were immunized with a depigmented and polymerized extract of D. pteronyssinus absorbed onto Aluminium hydroxide. The immunization process consisted of 3 subcutaneous injections containing 233.4 µg of freeze-dried extract. The administered doses were similar to those used in humans. Anti Der p 1 and Der p 2 antibodies were measured by ELISA in the sera of 4 rabbits. Anti Der p 1 (10B9) and anti Der p 2 (1D8) antibodies were coated, separately, to microtiter plates and incubated with a native D. pteronyssinus extract to bind the allergens. After washing, the plates were incubated with the rabbit sera. Recombinant Der p 2 was also used. As negative controls, the pre-immune sera of the rabbits and polyclonal sera against Fraxinus excelsior and Corylus avellana pollen extracts were used. RESULTS: All sera had high titres of specific IgG against Der p 1 and Der p 2 and rDer p 2. The specific IgG values in pre-immune and control sera were negative. CONCLUSIONS: Allergenic vaccines containing depigmented and polymerised D. pteronyssinus extracts induce specific antibodies against Der p 1 and Der p 2 at doses which are similar to those used in human treatment.
1074
TUESDAY
Reproducibility of Missing doses as a Predictor of Poor Medication Adherence in Patients Receiving Specific Immunotherapy P. A. Mahesh1, V. pudupakkam2, A. D. Holla3, V. Rajesh3; 1JSS Medical College, Mysore, INDIA, 2University of Colorado Health Sciences, Colorado, CO, 3Allergy Asthma and Chest Center, Mysore, INDIA. RATIONALE: In an earlier retrospective study we have observed that missing three doses or more in the last twenty doses of specific subcutaneous immunotherapy had a high likelihood of default. This study was conducted to observe the reproducibility of the earlier results in a prospective study in the same setting. METHODS: Inclusion criteria: All the patients who were receiving immunotherapy at the center in Dec 2003 at our center formed the cohort and were followed up until Jul 2005. Forty-nine patients were included in the study cohort. The number of missing doses in the last ten and last twenty doses was noted. Chi Square test was used to test for significant difference. RESULTS: Thirty-six males and 13 females formed the study cohort. Out of 49 patients, 7 dropped out of the program with a compliance rate of 85%. In the last ten doses, 30 (7.14 %) doses out of a possible 420 were missed in the compliant group compared to 27 (38.57 %) out of a possible 70 in the noncompliant group (p < 0.05). In the last twenty doses, 59 (7.02 %) doses out of a possible 840 were missed in the compliant group compared to 53 (37.85%) out of a possible 140 in the noncompliant group (p < 0.05). CONCLUSIONS: Missing doses is an important predictor of default. Missing more than 3 doses in last 20 doses has a high likelihood of default.
1075
Immunoregulatory Effects of Saccharomyces (S.) cerevisiae Mannan via Th2/Th3 Polarization in Mice J. M. Lehman, M. R. Streck, A. S. Tyagi, D. B. Lew; Pediatrics, University of Tennessee Health Science Center, Memphis, TN. RATIONALE: Lipoglycans from mycobacteria have been shown to stimulate IL-10-producing cells. Lipid modification of mannan causes multimeric engagement of mannose receptors and confers different biological effects. Mannan (Man9Gln) is the major component of the negatively charged outer wall of S. cerevisiae. Mannan from S. cerevisiae inhibits airway hyperreactivity in mice. Studies were conducted to investigate the effects of S. cerevisiae mannan on cytokine production in mice. METHODS: Naive FVB/N and Balb/c mice were given S. cerevisiae mannan (1 - 4 mg, 35-280 mg/kg) or vehicle via intranasally (i.n.) or gavage feeding (p.o.). After 18 hours the mice were sacrificed and superficial cervical lymph nodes (CLNs) and spleens were harvested. Whole CLNs and single cell suspensions of splenocytes were cultured for 72 hours with S. cerevisiae mannan (1mg/ml or saline). Cytokines were determined from the culture supernatants by Quantikine assay. The endotoxin levels of S. cerevisiae mannan were less than 2 EU/ml, measured by the Limulus assay. There were no detectable phospholipids by thin layer chromatography. RESULTS: IL-10 and TGFbeta production was increased two-fold in CLN- and splenocyte-cultures from both strains of mannan-treated mice (1mg, i.n.) compared to controls. Gavage feeding (0 - 4 mg) induced similar trends. There was a dose-dependent increase in IL-10 (30 - 90 pg/ml), IL-5 (70 - 250 pg/ml) and TGFbeta (2 - 4 ng/ml) (n = 4). No significant production of TNFalpha, IFNgamma, IL-4 or IL-12 was detected. CONCLUSIONS: A single dose of phospholipid-free mannan from S. cerevisiae, when given i.n. or p.o., renders systemic Th2/Th3 polarization in mice. Funding: LeBonheur, NIH, AAAAI
1072
Immunologic Changes after Long-Term Immunotherapy with Hop Japanese Pollen Extracts S. Lee1, S. Kim2, Y. Ye2, S. Kim3, S. Kim2, D. Nahm2, H. Park2; 1Internal Medicine, Dong-A University, Busan, REPUBLIC OF KOREA, 2Allergy and Rheumatology, Ajou University, Suwon, REPUBLIC OF KOREA, 3Internal Medicine, Seoul National University, Seoul, REPUBLIC OF KOREA. RATIONALE: Hop Japanese (Hop J) pollen has been considered as one of the major causative pollen allergens in the autumn season. We developed a new Hop J immunotherapy extract in collaboration with Allergopharma(Reinbeck, Germany) and investigated immunologic mechanisms during 3 yrs’ immunotherapy. METHODS: Twenty patients (13 asthma, 7 rhinitis) were enrolled from Ajou University Hospital. Sera were collected before, 1 yr, and 3 yrs after the immunotherapy. Changes of serum specific IgE, IgG1, and IgG4 levels to Hop J were monitored by ELISA. To evaluate cellular mechanisms, serum IL-10, IL-12, TGF1 and soluble CD23 levels were measured by ELISA. RESULTS: Specific IgG1 increased at 1 yr then decreased again at 3 yrs, and specific IgG4 levels increased continuously (p<0.05, respectively), whereas total and specific IgE levels showed variable responses with no statistical significance. IL-10, IL-12 TGF1 and soluble CD23 level significantly decreased during 3 yrs’ study period. (p<0.05 respectively). CONCLUSIONS: These findings suggest favorable effect of Hop J immunotherapy may be explained by IL-12 and TGF1 mediated immunomodulation and generation of blocking antibodies. This study was supported by a grant of the Korean Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (no. A050571) Funding: Ministry of Health & Welfare, Republic of Korea
1073
J ALLERGY CLIN IMMUNOL FEBRUARY 2006
Induction of Rabbit Specific IgG against Der p 1 and Der p 2 after Immunization with an Allergoid of Dermatophagoides Pteronyssinus E. Fernández-Caldas, M. Gallego, J. Carnés, M. Casanovas, V. Iraola; Laboratorios LETI S.L., Tres Cantos, SPAIN. RATIONALE: Immunotherapy with modified (depigmented and polymerized) extracts of D. pteronyssinus is an effective and safe treatment for allergic asthma and rhinoconjuntivitis. The objective of this study was to demonstrate the induction of specific IgG against Der p 1 and Der p 2 in the sera of rabbits previously immunized with modified extracts of D. pteronyssinus. METHODS: Four New Zealand White rabbits were immunized with a depigmented and polymerized extract of D. pteronyssinus absorbed onto Aluminium hydroxide. The immunization process consisted of 3 subcutaneous injections containing 233.4 µg of freeze-dried extract. The administered doses were similar to those used in humans. Anti Der p 1 and Der p 2 antibodies were measured by ELISA in the sera of 4 rabbits. Anti Der p 1 (10B9) and anti Der p 2 (1D8) antibodies were coated, separately, to microtiter plates and incubated with a native D. pteronyssinus extract to bind the allergens. After washing, the plates were incubated with the rabbit sera. Recombinant Der p 2 was also used. As negative controls, the pre-immune sera of the rabbits and polyclonal sera against Fraxinus excelsior and Corylus avellana pollen extracts were used. RESULTS: All sera had high titres of specific IgG against Der p 1 and Der p 2 and rDer p 2. The specific IgG values in pre-immune and control sera were negative. CONCLUSIONS: Allergenic vaccines containing depigmented and polymerised D. pteronyssinus extracts induce specific antibodies against Der p 1 and Der p 2 at doses which are similar to those used in human treatment.
1074
TUESDAY
Reproducibility of Missing doses as a Predictor of Poor Medication Adherence in Patients Receiving Specific Immunotherapy P. A. Mahesh1, V. pudupakkam2, A. D. Holla3, V. Rajesh3; 1JSS Medical College, Mysore, INDIA, 2University of Colorado Health Sciences, Colorado, CO, 3Allergy Asthma and Chest Center, Mysore, INDIA. RATIONALE: In an earlier retrospective study we have observed that missing three doses or more in the last twenty doses of specific subcutaneous immunotherapy had a high likelihood of default. This study was conducted to observe the reproducibility of the earlier results in a prospective study in the same setting. METHODS: Inclusion criteria: All the patients who were receiving immunotherapy at the center in Dec 2003 at our center formed the cohort and were followed up until Jul 2005. Forty-nine patients were included in the study cohort. The number of missing doses in the last ten and last twenty doses was noted. Chi Square test was used to test for significant difference. RESULTS: Thirty-six males and 13 females formed the study cohort. Out of 49 patients, 7 dropped out of the program with a compliance rate of 85%. In the last ten doses, 30 (7.14 %) doses out of a possible 420 were missed in the compliant group compared to 27 (38.57 %) out of a possible 70 in the noncompliant group (p < 0.05). In the last twenty doses, 59 (7.02 %) doses out of a possible 840 were missed in the compliant group compared to 53 (37.85%) out of a possible 140 in the noncompliant group (p < 0.05). CONCLUSIONS: Missing doses is an important predictor of default. Missing more than 3 doses in last 20 doses has a high likelihood of default.
1075