Guy Scadding - Academia.edu (original) (raw)

Papers by Guy Scadding

Research paper thumbnail of Mucosal antibody repertoires in allergy and the influence of allergen immunotherapy

Research paper thumbnail of Effect of grass pollen immunotherapy on clinical and local immune response to nasal allergen challenge

Allergy, Jan 14, 2015

Nasal allergen provocations may be useful in investigating the pathophysiology of allergic rhinit... more Nasal allergen provocations may be useful in investigating the pathophysiology of allergic rhinitis and effects of treatments. To use grass pollen nasal allergen challenge (NAC) to investigate the effects of allergen immunotherapy in a cross-sectional study. We studied nasal and cutaneous responses in untreated subjects with seasonal grass-pollen allergic rhinitis (n=14) compared with immunotherapy-treated allergics (n=14), plus a non-atopic control group (n=14). Volunteers underwent a standardised NAC with 2,000 BU Timothy grass allergen (equivalent to 1.3μg major allergen, Phl p5). Nasal fluid was collected and analysed by ImmunoCAP and multiplex assays. Clinical response was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Cutaneous response was measured by intradermal allergen injection. Retrospective seasonal symptom questionnaires were also completed. Immunotherapy-treated patients had lower symptom scores (p=0.04) and higher PNIF (p=0.02) after challenge tha...

Research paper thumbnail of Effector cell signature in peripheral blood following nasal allergen challenge in grass pollen allergic individuals

Allergy, 2015

Several studies have demonstrated the time course of inflammatory mediators in nasal fluids follo... more Several studies have demonstrated the time course of inflammatory mediators in nasal fluids following nasal allergen challenge (NAC), whereas the effects of NAC on cells in the periphery are unknown. We examined the time course of effector cell markers (for basophils, dendritic cells and T cells) in peripheral blood after nasal grass pollen allergen challenge. Twelve participants with seasonal allergic rhinitis underwent a control (diluent) challenge followed by NAC after an interval of 14 days. Nasal symptoms and peak nasal inspiratory flow (PNIF) were recorded along with peripheral basophil, T-cell and dendritic cell responses (flow cytometry), T-cell proliferative responses (thymidine incorporation), and cytokine expression (FluoroSpot assay). Robust increases in nasal symptoms and decreases in PNIF were observed during the early (0-1 h) response and modest significant changes during the late (1-24 h) response. Sequential peaks in peripheral blood basophil activation markers were...

Research paper thumbnail of Biomarkers of tolerance in response to allergen immunotherapy

Arbeiten aus dem Paul-Ehrlich-Institut (Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel) Langen/Hessen, 2013

Research paper thumbnail of Grass pollen nasal challenge is associated with increases in Th2 cytokines, Eotaxin, MDC and IL-6 in nasal fluid

Clinical and Translational Allergy, 2013

Research paper thumbnail of Seasonal increases in peripheral innate lymphoid type 2 cells are inhibited by subcutaneous grass pollen immunotherapy

Journal of Allergy and Clinical Immunology, 2014

Research paper thumbnail of Local and systemic effects of cat allergen nasal provocation

Clinical & Experimental Allergy, 2014

Background: Cat allergen is widely distributed in homes and schools; allergic sensitisation is co... more Background: Cat allergen is widely distributed in homes and schools; allergic sensitisation is common.

Research paper thumbnail of Immediate-type food allergy to balsam of Peru

Clinical and Translational Allergy, 2011

Research paper thumbnail of Positive food challenges despite negative specific IgE testing

Clinical and Translational Allergy, 2011

Research paper thumbnail of Silk contact anaphylaxis

Research paper thumbnail of Basophil expression of diamine oxidase: A novel biomarker of allergen immunotherapy response

Journal of Allergy and Clinical Immunology, 2014

Immunotherapy inhibits basophil histamine release, but the assay is cumbersome, and no one has st... more Immunotherapy inhibits basophil histamine release, but the assay is cumbersome, and no one has studied the effects of immunotherapy withdrawal. Intracellular fluorochrome-labeled diamine oxidase (DAO) was used as a novel functional readout of basophil histamine release after immunotherapy. Results were compared with conventional basophil surface expression of activation markers. Subcutaneous immunotherapy (SCIT)-treated patients (n = 14), sublingual immunotherapy (SLIT)-treated patients (n = 12), participants who completed 3 years of treatment with grass pollen sublingual immunotherapy (the SLIT-TOL group; n = 6), patients with untreated seasonal allergic rhinitis (SAR; n = 24), and nonatopic control subjects (n = 12) were studied. Intracellularly labeled DAO(+) and surface expression of CD203c(bright), CD63(+), and CD107a(+) on chemoattractant receptor-homologous molecule expressed on TH2 lymphocytes (CRTh2)-positive basophils were measured by means of flow cytometry. Serum IgG4 levels and serum inhibitory activity for IgE-allergen complex binding to B cells (IgE-FAB) and basophil histamine release were also determined. Proportions of allergen-stimulated DAO(+)CRTh2(+) basophils were higher in participants in the SCIT, SLIT, and SLIT-TOL groups (all P < .0001) compared with those in patients in the SAR group. Similarly, there were lower proportions of CRTh2(+) basophils expressing surface CD203c(bright) (all P < .001), CD63 (all P < .001), and CD107a (all P < .01). Rhinitis symptoms were lower in the SCIT, SLIT, and SLIT-TOL groups (P < .001) compared with those in the SAR group. Serum inhibitory activity for IgE-FAB and basophil histamine release were also significantly greater in all immunotherapy groups (P < .05) compared with the SAR group. These results support long-term clinical and immunologic tolerance during and after grass pollen immunotherapy. Intracellularly labeled DAO expression by basophils merits further investigation as a surrogate biomarker for monitoring efficacy and tolerance after immunotherapy.

Research paper thumbnail of Optimisation of grass pollen nasal allergen challenge for assessment of clinical and immunological outcomes

Journal of Immunological Methods, 2012

Nasal allergen challenge can be used to assess the clinical and immunological aspects of rhinitis... more Nasal allergen challenge can be used to assess the clinical and immunological aspects of rhinitis due to inhalant allergens. We aimed to develop a reproducible technique for grass pollen nasal allergen challenge and to study biomarkers within nasal secretions. 20 Grass pollen allergic individuals underwent nasal challenges with purified Timothy grass allergen. An initial dose-titration challenge was used to determine dose-response characteristics. Subsequently, volunteers underwent 3 further challenges using individualised threshold doses. Symptom scores, visual analogue scores, and peak nasal inspiratory flow (PNIF) were recorded at baseline and up to 6h after challenge. Nasal secretions were collected at each time point using synthetic filter papers or absorptive polyurethane sponges and analysed for IL-4, -5, -10, -13, IFN-γ, Tryptase and Eosinophil Cationic Protein (ECP). Challenges gave reproducible symptom scores and decreased PNIF. Tryptase levels in nasal fluid peaked at 5 min after challenge and returned to baseline levels at 1h. ECP, IL-5, IL-13 and IL-4 levels were increased from 2-3 h and showed progressive increases to 5-6 h. Sponges proved the superior nasal fluid sampling technique. We have developed a reproducible nasal allergen challenge technique. This may be used as a surrogate clinical endpoint in trials assessing the efficacy of treatments for allergic rhinitis. Tryptase in local nasal secretions is a potential biomarker of the early phase response; ECP and the Th2 cytokines IL-5, -13 and -4 markers of late phase allergic responses. Our model allows correlation between clinical responses and local biomarkers following nasal allergen challenge.

Research paper thumbnail of Mechanisms of Sublingual Immunotherapy

Journal of Asthma, 2009

Allergen-specific sublingual immunotherapy is now recognized to be an efficacious and well-tolera... more Allergen-specific sublingual immunotherapy is now recognized to be an efficacious and well-tolerated treatment for allergic rhinitis. Emerging treatment strategies are also aimed at the primary treatment of allergic asthma, particularly allergy to house dust mites. Knowledge of the exact mechanisms of action of sublingual immunotherapy is at a basic level, although there appear to be similarities to the immunological changes seen in subcutaneous immunotherapy. An improved understanding should allow the development of more effective treatment programs and widen the potential use of this form of immunotherapy. This review discusses the possible mechanism of action of sublingual immunotherapy, including data from animal and clinical studies, while comparing this with the current understanding of subcutaneous immunotherapy.

Research paper thumbnail of IL-35+ Regulatory T Cells Suppress Grass Pollen-Driven Th2 Responses and Are Induced Following Grass Pollen-Specific Sublingual Immunotherapy

Journal of Allergy and Clinical Immunology, 2013

Research paper thumbnail of Interleukin-35 Suppresses Allergen-specific Th2 Response in Patients with Grass pollen induced Seasonal Allergic Rhinitis

Journal of Allergy and Clinical Immunology, 2012

Research paper thumbnail of Peri-operative cardiac arrest with ST elevation secondary to gelofusin anaphylaxis — Kounis syndrome in the anaesthetic room

International Journal of Cardiology, 2013

Research paper thumbnail of Dropouts in sublingual allergen immunotherapy trials - a systematic review

Allergy, 2014

Participant dropouts can reduce the power of allergen immunotherapy clinical trials. Evaluation o... more Participant dropouts can reduce the power of allergen immunotherapy clinical trials. Evaluation of the dropout rate and reasons for dropout are important not only in the planning of clinical studies but are also relevant for adherence to immunotherapy in daily clinical practice. A systematic review was carried out in order to establish the overall dropout rate among published double-blind, placebo-controlled randomized clinical trials of sublingual immunotherapy for respiratory allergic diseases. Dropouts were analysed in regards to allergen, formulation, treatment schedule, participant age, study size, number of centres and type of allergic disease. Relative dropout rates in placebo and active groups as well as reasons for dropout were also assessed. A total of 81 studies, comprising 9998 patients, were included. Dropout rates in sublingual immunotherapy controlled studies do not appear to be a major problem with a composite dropout percentage of 14% (95% CI:11.9-16). Furthermore, they are not different for active compared to placebo-treated participants. This lends support to the positive clinical outcomes seen in meta-analyses of these trials.

Research paper thumbnail of CC Chemokine Receptor 4 (CCR4) in human allergen-induced late nasal responses

Allergy, 2010

Background-CC Chemokine receptor 4 (CCR4) is preferentially expressed on Th2 lymphocytes. CCR4-me... more Background-CC Chemokine receptor 4 (CCR4) is preferentially expressed on Th2 lymphocytes. CCR4-mediated inflammation may be important in the pathology of allergic rhinitis. Disruption of CCR4 -ligand interaction may abrogate allergen-induced inflammation.

Research paper thumbnail of Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3-expressing cells and elevated allergen-specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E-facilitated allergen binding to B cells

Clinical & Experimental Allergy, 2010

Background The mechanisms of sublingual immunotherapy (SLIT) are less well understood than those ... more Background The mechanisms of sublingual immunotherapy (SLIT) are less well understood than those of subcutaneous immunotherapy (SCIT). Objectives To determine the effects of grass-pollen SLIT on oral mucosal immune cells, local regulatory cytokines, serum allergen-specific antibody subclasses and B cell IgE-facilitated allergen binding (IgE-FAB). Methods Biopsies from the sublingual mucosa of up to 14 SLIT-treated atopics, nine placebotreated atopics and eight normal controls were examined for myeloid dendritic cells (mDCs) (CD1c), plasmacytoid dendritic cells (CD303), mast cells (AA1), T cells (CD3) and Foxp3 using immunofluorescence microscopy. IL-10 and TGF-b mRNA expression were identified by in situ hybridization. Allergen-specific IgG and IgA subclasses and serum inhibitory activity for binding of allergen-IgE complexes to B cells (IgE-FAB) were measured before, during and on the completion of SLIT. Results Foxp3 1 cells were increased in the oral epithelium of SLIT-vs. placebo-treated atopics (P = 0.04). Greater numbers of subepithelial mDCs were present in placebo-treated, but not in SLIT-treated, atopics compared with normal controls (P = 0.05). There were fewer subepithelial mast cells and greater epithelial T cells in SLIT-compared with placebo-treated atopics (P = 0.1 for both). IgG 1 and IgG 4 were increased following SLIT (Po0.001). Peak seasonal IgA 1 and IgA 2 were increased during SLIT (Po0.05). There was a time-dependent increase in serum inhibitory activity for IgE-FAB in SLIT-treated atopics. Conclusions SLIT with grass pollen extract is associated with increased Foxp3 1 cells in the sublingual epithelium and systemic humoral changes as observed previously for SCIT.

Research paper thumbnail of Mucosal antibody repertoires in allergy and the influence of allergen immunotherapy

Research paper thumbnail of Effect of grass pollen immunotherapy on clinical and local immune response to nasal allergen challenge

Allergy, Jan 14, 2015

Nasal allergen provocations may be useful in investigating the pathophysiology of allergic rhinit... more Nasal allergen provocations may be useful in investigating the pathophysiology of allergic rhinitis and effects of treatments. To use grass pollen nasal allergen challenge (NAC) to investigate the effects of allergen immunotherapy in a cross-sectional study. We studied nasal and cutaneous responses in untreated subjects with seasonal grass-pollen allergic rhinitis (n=14) compared with immunotherapy-treated allergics (n=14), plus a non-atopic control group (n=14). Volunteers underwent a standardised NAC with 2,000 BU Timothy grass allergen (equivalent to 1.3μg major allergen, Phl p5). Nasal fluid was collected and analysed by ImmunoCAP and multiplex assays. Clinical response was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Cutaneous response was measured by intradermal allergen injection. Retrospective seasonal symptom questionnaires were also completed. Immunotherapy-treated patients had lower symptom scores (p=0.04) and higher PNIF (p=0.02) after challenge tha...

Research paper thumbnail of Effector cell signature in peripheral blood following nasal allergen challenge in grass pollen allergic individuals

Allergy, 2015

Several studies have demonstrated the time course of inflammatory mediators in nasal fluids follo... more Several studies have demonstrated the time course of inflammatory mediators in nasal fluids following nasal allergen challenge (NAC), whereas the effects of NAC on cells in the periphery are unknown. We examined the time course of effector cell markers (for basophils, dendritic cells and T cells) in peripheral blood after nasal grass pollen allergen challenge. Twelve participants with seasonal allergic rhinitis underwent a control (diluent) challenge followed by NAC after an interval of 14 days. Nasal symptoms and peak nasal inspiratory flow (PNIF) were recorded along with peripheral basophil, T-cell and dendritic cell responses (flow cytometry), T-cell proliferative responses (thymidine incorporation), and cytokine expression (FluoroSpot assay). Robust increases in nasal symptoms and decreases in PNIF were observed during the early (0-1 h) response and modest significant changes during the late (1-24 h) response. Sequential peaks in peripheral blood basophil activation markers were...

Research paper thumbnail of Biomarkers of tolerance in response to allergen immunotherapy

Arbeiten aus dem Paul-Ehrlich-Institut (Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel) Langen/Hessen, 2013

Research paper thumbnail of Grass pollen nasal challenge is associated with increases in Th2 cytokines, Eotaxin, MDC and IL-6 in nasal fluid

Clinical and Translational Allergy, 2013

Research paper thumbnail of Seasonal increases in peripheral innate lymphoid type 2 cells are inhibited by subcutaneous grass pollen immunotherapy

Journal of Allergy and Clinical Immunology, 2014

Research paper thumbnail of Local and systemic effects of cat allergen nasal provocation

Clinical & Experimental Allergy, 2014

Background: Cat allergen is widely distributed in homes and schools; allergic sensitisation is co... more Background: Cat allergen is widely distributed in homes and schools; allergic sensitisation is common.

Research paper thumbnail of Immediate-type food allergy to balsam of Peru

Clinical and Translational Allergy, 2011

Research paper thumbnail of Positive food challenges despite negative specific IgE testing

Clinical and Translational Allergy, 2011

Research paper thumbnail of Silk contact anaphylaxis

Research paper thumbnail of Basophil expression of diamine oxidase: A novel biomarker of allergen immunotherapy response

Journal of Allergy and Clinical Immunology, 2014

Immunotherapy inhibits basophil histamine release, but the assay is cumbersome, and no one has st... more Immunotherapy inhibits basophil histamine release, but the assay is cumbersome, and no one has studied the effects of immunotherapy withdrawal. Intracellular fluorochrome-labeled diamine oxidase (DAO) was used as a novel functional readout of basophil histamine release after immunotherapy. Results were compared with conventional basophil surface expression of activation markers. Subcutaneous immunotherapy (SCIT)-treated patients (n = 14), sublingual immunotherapy (SLIT)-treated patients (n = 12), participants who completed 3 years of treatment with grass pollen sublingual immunotherapy (the SLIT-TOL group; n = 6), patients with untreated seasonal allergic rhinitis (SAR; n = 24), and nonatopic control subjects (n = 12) were studied. Intracellularly labeled DAO(+) and surface expression of CD203c(bright), CD63(+), and CD107a(+) on chemoattractant receptor-homologous molecule expressed on TH2 lymphocytes (CRTh2)-positive basophils were measured by means of flow cytometry. Serum IgG4 levels and serum inhibitory activity for IgE-allergen complex binding to B cells (IgE-FAB) and basophil histamine release were also determined. Proportions of allergen-stimulated DAO(+)CRTh2(+) basophils were higher in participants in the SCIT, SLIT, and SLIT-TOL groups (all P < .0001) compared with those in patients in the SAR group. Similarly, there were lower proportions of CRTh2(+) basophils expressing surface CD203c(bright) (all P < .001), CD63 (all P < .001), and CD107a (all P < .01). Rhinitis symptoms were lower in the SCIT, SLIT, and SLIT-TOL groups (P < .001) compared with those in the SAR group. Serum inhibitory activity for IgE-FAB and basophil histamine release were also significantly greater in all immunotherapy groups (P < .05) compared with the SAR group. These results support long-term clinical and immunologic tolerance during and after grass pollen immunotherapy. Intracellularly labeled DAO expression by basophils merits further investigation as a surrogate biomarker for monitoring efficacy and tolerance after immunotherapy.

Research paper thumbnail of Optimisation of grass pollen nasal allergen challenge for assessment of clinical and immunological outcomes

Journal of Immunological Methods, 2012

Nasal allergen challenge can be used to assess the clinical and immunological aspects of rhinitis... more Nasal allergen challenge can be used to assess the clinical and immunological aspects of rhinitis due to inhalant allergens. We aimed to develop a reproducible technique for grass pollen nasal allergen challenge and to study biomarkers within nasal secretions. 20 Grass pollen allergic individuals underwent nasal challenges with purified Timothy grass allergen. An initial dose-titration challenge was used to determine dose-response characteristics. Subsequently, volunteers underwent 3 further challenges using individualised threshold doses. Symptom scores, visual analogue scores, and peak nasal inspiratory flow (PNIF) were recorded at baseline and up to 6h after challenge. Nasal secretions were collected at each time point using synthetic filter papers or absorptive polyurethane sponges and analysed for IL-4, -5, -10, -13, IFN-γ, Tryptase and Eosinophil Cationic Protein (ECP). Challenges gave reproducible symptom scores and decreased PNIF. Tryptase levels in nasal fluid peaked at 5 min after challenge and returned to baseline levels at 1h. ECP, IL-5, IL-13 and IL-4 levels were increased from 2-3 h and showed progressive increases to 5-6 h. Sponges proved the superior nasal fluid sampling technique. We have developed a reproducible nasal allergen challenge technique. This may be used as a surrogate clinical endpoint in trials assessing the efficacy of treatments for allergic rhinitis. Tryptase in local nasal secretions is a potential biomarker of the early phase response; ECP and the Th2 cytokines IL-5, -13 and -4 markers of late phase allergic responses. Our model allows correlation between clinical responses and local biomarkers following nasal allergen challenge.

Research paper thumbnail of Mechanisms of Sublingual Immunotherapy

Journal of Asthma, 2009

Allergen-specific sublingual immunotherapy is now recognized to be an efficacious and well-tolera... more Allergen-specific sublingual immunotherapy is now recognized to be an efficacious and well-tolerated treatment for allergic rhinitis. Emerging treatment strategies are also aimed at the primary treatment of allergic asthma, particularly allergy to house dust mites. Knowledge of the exact mechanisms of action of sublingual immunotherapy is at a basic level, although there appear to be similarities to the immunological changes seen in subcutaneous immunotherapy. An improved understanding should allow the development of more effective treatment programs and widen the potential use of this form of immunotherapy. This review discusses the possible mechanism of action of sublingual immunotherapy, including data from animal and clinical studies, while comparing this with the current understanding of subcutaneous immunotherapy.

Research paper thumbnail of IL-35+ Regulatory T Cells Suppress Grass Pollen-Driven Th2 Responses and Are Induced Following Grass Pollen-Specific Sublingual Immunotherapy

Journal of Allergy and Clinical Immunology, 2013

Research paper thumbnail of Interleukin-35 Suppresses Allergen-specific Th2 Response in Patients with Grass pollen induced Seasonal Allergic Rhinitis

Journal of Allergy and Clinical Immunology, 2012

Research paper thumbnail of Peri-operative cardiac arrest with ST elevation secondary to gelofusin anaphylaxis — Kounis syndrome in the anaesthetic room

International Journal of Cardiology, 2013

Research paper thumbnail of Dropouts in sublingual allergen immunotherapy trials - a systematic review

Allergy, 2014

Participant dropouts can reduce the power of allergen immunotherapy clinical trials. Evaluation o... more Participant dropouts can reduce the power of allergen immunotherapy clinical trials. Evaluation of the dropout rate and reasons for dropout are important not only in the planning of clinical studies but are also relevant for adherence to immunotherapy in daily clinical practice. A systematic review was carried out in order to establish the overall dropout rate among published double-blind, placebo-controlled randomized clinical trials of sublingual immunotherapy for respiratory allergic diseases. Dropouts were analysed in regards to allergen, formulation, treatment schedule, participant age, study size, number of centres and type of allergic disease. Relative dropout rates in placebo and active groups as well as reasons for dropout were also assessed. A total of 81 studies, comprising 9998 patients, were included. Dropout rates in sublingual immunotherapy controlled studies do not appear to be a major problem with a composite dropout percentage of 14% (95% CI:11.9-16). Furthermore, they are not different for active compared to placebo-treated participants. This lends support to the positive clinical outcomes seen in meta-analyses of these trials.

Research paper thumbnail of CC Chemokine Receptor 4 (CCR4) in human allergen-induced late nasal responses

Allergy, 2010

Background-CC Chemokine receptor 4 (CCR4) is preferentially expressed on Th2 lymphocytes. CCR4-me... more Background-CC Chemokine receptor 4 (CCR4) is preferentially expressed on Th2 lymphocytes. CCR4-mediated inflammation may be important in the pathology of allergic rhinitis. Disruption of CCR4 -ligand interaction may abrogate allergen-induced inflammation.

Research paper thumbnail of Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3-expressing cells and elevated allergen-specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E-facilitated allergen binding to B cells

Clinical & Experimental Allergy, 2010

Background The mechanisms of sublingual immunotherapy (SLIT) are less well understood than those ... more Background The mechanisms of sublingual immunotherapy (SLIT) are less well understood than those of subcutaneous immunotherapy (SCIT). Objectives To determine the effects of grass-pollen SLIT on oral mucosal immune cells, local regulatory cytokines, serum allergen-specific antibody subclasses and B cell IgE-facilitated allergen binding (IgE-FAB). Methods Biopsies from the sublingual mucosa of up to 14 SLIT-treated atopics, nine placebotreated atopics and eight normal controls were examined for myeloid dendritic cells (mDCs) (CD1c), plasmacytoid dendritic cells (CD303), mast cells (AA1), T cells (CD3) and Foxp3 using immunofluorescence microscopy. IL-10 and TGF-b mRNA expression were identified by in situ hybridization. Allergen-specific IgG and IgA subclasses and serum inhibitory activity for binding of allergen-IgE complexes to B cells (IgE-FAB) were measured before, during and on the completion of SLIT. Results Foxp3 1 cells were increased in the oral epithelium of SLIT-vs. placebo-treated atopics (P = 0.04). Greater numbers of subepithelial mDCs were present in placebo-treated, but not in SLIT-treated, atopics compared with normal controls (P = 0.05). There were fewer subepithelial mast cells and greater epithelial T cells in SLIT-compared with placebo-treated atopics (P = 0.1 for both). IgG 1 and IgG 4 were increased following SLIT (Po0.001). Peak seasonal IgA 1 and IgA 2 were increased during SLIT (Po0.05). There was a time-dependent increase in serum inhibitory activity for IgE-FAB in SLIT-treated atopics. Conclusions SLIT with grass pollen extract is associated with increased Foxp3 1 cells in the sublingual epithelium and systemic humoral changes as observed previously for SCIT.