- Email: [email protected]
Immunological Mechanisem of Sublingual Immunotherapy
AB202 Abstracts
721
MONDAY
Local Nasal 'Protective' Immunoglobulin G4 (IgG4) Responses in Nasal Fluid Following Grass Pollen Sublingual Immunotherapy Nausheen Saleem, BSc(Hons)1, Adam Chaker, MD1,2,3, Ulrich Zissler4, Carsten B. Schmidt-Weber, PhD1, Stephen R. Durham, MA, MD, FRCP5,6, Mohamed H. Shamji, BSc, MSc, PhD7,8; 1Imperial College London, 2Universitatsklinkum Dusseldorf, Dusseldorf, Germany, 3ENT department, TU Munich, M€unchen, Germany, 4ENT department, TU Munich, 5Imperial College, London, United Kingdom, 6Medical Research Council and Asthma UK Centre for Allergic Mechanisms of Asthma, UK, 7 MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, 8Imperial College London, United Kingdom. RATIONALE: Grass pollen sublingual immunotherapy (SLIT) is associated with induction of serum IgG4-associated blocking antibodies that prevent IgE-facilitated allergen binding to B cells (IgE-FAB). We hypothesised that local nasal inhibitory IgG4 antibodies are also induced following SLIT. METHODS: Nasal fluids were obtained from SLIT-treated patients (n57), untreated allergics (n57) and non-atopic controls (n58). Specific IgE and IgG4 to Phleum pratense (Phl p) components were measured by ISAC microarray technology. Inhibitory activity of nasal fluid and serum was measured using the IgE-FAB assay. RESULTS: Untreated allergics had elevated levels of rPhl p 1 (p50.01) and rPhl p 5-specific IgE in nasal fluid compared to non-atopic controls. SLIT-treated patients showed a trend for an increase in rPhl p 1 (mean+/SE, 6.062.7 ISU) and rPhl p 5-specific IgE (2.162.6 ISU) compared to untreated allergics (p50.12). Recombinant Phl p 5-specific IgG4 levels were increased in SLIT-treated patients compared to untreated allergics (p50.02) and non-atopic controls (p50.003). Inhibitory activity in nasal fluid for co-operative binding of allergen-IgE complexes to B cells in SLITtreated patients was significantly reduced (p50.004) compared to untreated allergics. These decreases in local nasal inhibitory activity paralleled reductions in serum inhibitory activity after SLIT (p50.03). Interestingly, the magnitude of this suppression was more profound with local antibodies (45%) compared to the peripheral antibody responses (35%). CONCLUSIONS: For the first time, IgG4 antibodies with inhibitory activity for IgE-FAB were measured in the nasal fluid of SLIT treated patients. Local IgG4 antibodies may potentially be used as a surrogate/ predictive biomarker for monitoring SLIT.
722
Antigen-Specific TH Cell Monitoring by CD154 Expression in Japanese Cedar-Specific SCIT T. Nomura1,2, I. Tsuge1, C. Inuo1, Y. Nakajima1, K. Tanaka1, N. Naruse3, S. Suzuki3, H. Ando3, Y. Kondo3, S. Saitoh2, A. Urisu3; 1Department of Pediatrics, School of Medicine, Fujita Health University, Toyoake, Japan, 2 Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan, 3Department of Pediatrics, The Second Teaching Hospital, Fujita Health University, Nagoya, Japan. RATIONALE: The involvement of a shift from TH2 to TH1 responses in the peripheral blood in pollen-specific subcutaneous immunotherapy (SCIT) has been contentious, partly because of difficulties analyzing antigen-specific TH cells. This study aimed to use recent technical advances to establish more direct and simple method to analyze antigen-specific TH cells and to clarify the involvement of a TH2/TH1 shift in the peripheral blood in pollen-specific immunotherapy. METHODS: In the pollen season 2012, after short-term (6 h) antigen stimulation, antigen-specific TH cells in the peripheral blood of Japanese children and young adults with Japanese cedar pollinosis undergoing SCIT were analyzed by multicolor flow cytometry for the presence of the activation marker CD154 and intracellular cytokines. RESULTS: Thirty-nine patients aged between 5 and 22 years were enrolled in the study; 22 were in their first pollen season with SCIT (SCIT1 group), 11 were in their second pollen season with SCIT (SCIT2 group) and remaining 6 were planning to start SCIT (control group). The number
J ALLERGY CLIN IMMUNOL FEBRUARY 2013
of Japanese cedar-specific IL-5-, IL-4-, IFN-g-, IL-17A-, IL-10- and TNF-a-producing TH cells without antigen-driven cell proliferation was determined. Decreased number of Japanese cedar-specific IL-5- and IL4-producing TH cells were seen in the SCIT1 and SCIT2 group compared with in the control group (P < 0.005 for all). CONCLUSIONS: We established a more direct and simple method to analyze antigen-specific TH cells and showed a shift from TH2 to TH1 responses in the peripheral blood of patients with Japanese cedar pollinosis undergoing SCIT.
723
Immunological Mechanisem of Sublingual Immunotherapy Reza Farid, MD, FAAAAI1, Farahzad Jabbari2, Homa Sadri3; 1 Allergy Research Center, Mashhad University of Medical Sciences, 2 Mashhad university, Mashhad, Iran, 3Mashhad Universiti, Mashhad, Iran. RATIONALE: Sensitivity to house dust mite allergens in the development of allergic rhinitis is very common. However there is rare double blind placebo contro study (DBPCT) for evaluation of SLIT in treatment of allergic rhinitis in our study area. OBJECTIVE: This study compared the clinical and immunological effects of high dose Dermatophagoides farinae vaccine versus placeboes. METHODS: Forty poly-sensitized patients with allergic rhinitis, all of them sensitive to mite, aged from 6 to 33 year were enrolled into the study. Twenty one patients in the active group and 19 received placebo via sublingual administration for 6 months. mRNA expression levels of IL-10, TGF-b , FoxP3 and IL-17were measured by using real-time PCR before and after of SLIT. Clinical efficacy estimated by the reduction rate of symptom/medication scores in active group compared with placebo treatment. RESULTS: Clinical efficacy was supported by significant reduction of symptom/medication scores in active group compared with placebo group. No severe systemic reactions were noted. After 6 months’ active SLIT, TGF-b mRNA expression levels were increased compared with pretreatment (P <0.01) and FoxP3 mRNA expression levels were increased compared with placebo group. (P < 0.05). CONCLUSIONS: SLIT with Dermatophagoides farina extracts is an effective treatment in poly-sensitized patients with allergic rhinitis.TGF-bmediated T-cell suppression may be an important mechanism in the first 6 months of SLIT.
721
MONDAY
Local Nasal 'Protective' Immunoglobulin G4 (IgG4) Responses in Nasal Fluid Following Grass Pollen Sublingual Immunotherapy Nausheen Saleem, BSc(Hons)1, Adam Chaker, MD1,2,3, Ulrich Zissler4, Carsten B. Schmidt-Weber, PhD1, Stephen R. Durham, MA, MD, FRCP5,6, Mohamed H. Shamji, BSc, MSc, PhD7,8; 1Imperial College London, 2Universitatsklinkum Dusseldorf, Dusseldorf, Germany, 3ENT department, TU Munich, M€unchen, Germany, 4ENT department, TU Munich, 5Imperial College, London, United Kingdom, 6Medical Research Council and Asthma UK Centre for Allergic Mechanisms of Asthma, UK, 7 MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, 8Imperial College London, United Kingdom. RATIONALE: Grass pollen sublingual immunotherapy (SLIT) is associated with induction of serum IgG4-associated blocking antibodies that prevent IgE-facilitated allergen binding to B cells (IgE-FAB). We hypothesised that local nasal inhibitory IgG4 antibodies are also induced following SLIT. METHODS: Nasal fluids were obtained from SLIT-treated patients (n57), untreated allergics (n57) and non-atopic controls (n58). Specific IgE and IgG4 to Phleum pratense (Phl p) components were measured by ISAC microarray technology. Inhibitory activity of nasal fluid and serum was measured using the IgE-FAB assay. RESULTS: Untreated allergics had elevated levels of rPhl p 1 (p50.01) and rPhl p 5-specific IgE in nasal fluid compared to non-atopic controls. SLIT-treated patients showed a trend for an increase in rPhl p 1 (mean+/SE, 6.062.7 ISU) and rPhl p 5-specific IgE (2.162.6 ISU) compared to untreated allergics (p50.12). Recombinant Phl p 5-specific IgG4 levels were increased in SLIT-treated patients compared to untreated allergics (p50.02) and non-atopic controls (p50.003). Inhibitory activity in nasal fluid for co-operative binding of allergen-IgE complexes to B cells in SLITtreated patients was significantly reduced (p50.004) compared to untreated allergics. These decreases in local nasal inhibitory activity paralleled reductions in serum inhibitory activity after SLIT (p50.03). Interestingly, the magnitude of this suppression was more profound with local antibodies (45%) compared to the peripheral antibody responses (35%). CONCLUSIONS: For the first time, IgG4 antibodies with inhibitory activity for IgE-FAB were measured in the nasal fluid of SLIT treated patients. Local IgG4 antibodies may potentially be used as a surrogate/ predictive biomarker for monitoring SLIT.
722
Antigen-Specific TH Cell Monitoring by CD154 Expression in Japanese Cedar-Specific SCIT T. Nomura1,2, I. Tsuge1, C. Inuo1, Y. Nakajima1, K. Tanaka1, N. Naruse3, S. Suzuki3, H. Ando3, Y. Kondo3, S. Saitoh2, A. Urisu3; 1Department of Pediatrics, School of Medicine, Fujita Health University, Toyoake, Japan, 2 Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan, 3Department of Pediatrics, The Second Teaching Hospital, Fujita Health University, Nagoya, Japan. RATIONALE: The involvement of a shift from TH2 to TH1 responses in the peripheral blood in pollen-specific subcutaneous immunotherapy (SCIT) has been contentious, partly because of difficulties analyzing antigen-specific TH cells. This study aimed to use recent technical advances to establish more direct and simple method to analyze antigen-specific TH cells and to clarify the involvement of a TH2/TH1 shift in the peripheral blood in pollen-specific immunotherapy. METHODS: In the pollen season 2012, after short-term (6 h) antigen stimulation, antigen-specific TH cells in the peripheral blood of Japanese children and young adults with Japanese cedar pollinosis undergoing SCIT were analyzed by multicolor flow cytometry for the presence of the activation marker CD154 and intracellular cytokines. RESULTS: Thirty-nine patients aged between 5 and 22 years were enrolled in the study; 22 were in their first pollen season with SCIT (SCIT1 group), 11 were in their second pollen season with SCIT (SCIT2 group) and remaining 6 were planning to start SCIT (control group). The number
J ALLERGY CLIN IMMUNOL FEBRUARY 2013
of Japanese cedar-specific IL-5-, IL-4-, IFN-g-, IL-17A-, IL-10- and TNF-a-producing TH cells without antigen-driven cell proliferation was determined. Decreased number of Japanese cedar-specific IL-5- and IL4-producing TH cells were seen in the SCIT1 and SCIT2 group compared with in the control group (P < 0.005 for all). CONCLUSIONS: We established a more direct and simple method to analyze antigen-specific TH cells and showed a shift from TH2 to TH1 responses in the peripheral blood of patients with Japanese cedar pollinosis undergoing SCIT.
723
Immunological Mechanisem of Sublingual Immunotherapy Reza Farid, MD, FAAAAI1, Farahzad Jabbari2, Homa Sadri3; 1 Allergy Research Center, Mashhad University of Medical Sciences, 2 Mashhad university, Mashhad, Iran, 3Mashhad Universiti, Mashhad, Iran. RATIONALE: Sensitivity to house dust mite allergens in the development of allergic rhinitis is very common. However there is rare double blind placebo contro study (DBPCT) for evaluation of SLIT in treatment of allergic rhinitis in our study area. OBJECTIVE: This study compared the clinical and immunological effects of high dose Dermatophagoides farinae vaccine versus placeboes. METHODS: Forty poly-sensitized patients with allergic rhinitis, all of them sensitive to mite, aged from 6 to 33 year were enrolled into the study. Twenty one patients in the active group and 19 received placebo via sublingual administration for 6 months. mRNA expression levels of IL-10, TGF-b , FoxP3 and IL-17were measured by using real-time PCR before and after of SLIT. Clinical efficacy estimated by the reduction rate of symptom/medication scores in active group compared with placebo treatment. RESULTS: Clinical efficacy was supported by significant reduction of symptom/medication scores in active group compared with placebo group. No severe systemic reactions were noted. After 6 months’ active SLIT, TGF-b mRNA expression levels were increased compared with pretreatment (P <0.01) and FoxP3 mRNA expression levels were increased compared with placebo group. (P < 0.05). CONCLUSIONS: SLIT with Dermatophagoides farina extracts is an effective treatment in poly-sensitized patients with allergic rhinitis.TGF-bmediated T-cell suppression may be an important mechanism in the first 6 months of SLIT.