Clinical and Immunologic Changes due to Subcutaneous Immunotherapy With Cat and Dog Extracts Using an Ultrarush Up-Dosing Phase: A Real-Life Study

Objective: We aimed to evaluate the efficacy of and immunologic changes caused by subcutaneous immunotherapy (SCIT) in patients with allergy to cat and dog. Methods: The study population comprised patients with rhinitis and/or asthma and allergy to cat or dog from a previous safety study. All patients had specific IgE to cat and/or dog. The SCIT maintenance dose was administered using an infusion pump over a single 4-hour session, followed by monthly administration over 6 months. Data were gathered on clinical outcomes, pulmonary function, FeNO, rhinitis and asthma symptoms, quality of life (QOL), and scores for the Asthma Control Test and symptom visual analog scale were recorded at baseline and then at 1, 3, and 6 months. Specific IgE and IgG antibody responses to cat and dog allergens were determined. Results: The study population comprised 61 patients with a mean age of 35.6 (9.7) years, of whom 40 underwent SCIT for at allergy. A significant improvement was observed in rhinitis and asthma symptoms and in QOL, use of medication, visual analog scale score, and Asthma Control Test score at 1 month; these improvements persisted at month 6. The clinical improvement with cat extract was significantly more marked than with dog extract. Nearly half of the patients (49.09%) had an increase of &gt;0.9 in the ESPRINT-15 QOL in allergic rhinitis questionnaire, and 58.18% had an increase of &gt;0.5 in the Asthma Quality of Life Questionnaire score at month 6. Both differences represent the minimal clinical important difference. A significant increase was observed in specific IgG and IgE to different allergens at 3 and/or 6 months. Conclusions: Ultrarush SCIT with cat and dog extracts has substantial clinical value for many patients.</jats:p

Sublingual allergen immunotherapy with recombinant dog allergens prevents airway hyperresponsiveness in a model of asthma marked by vigorous T_H2 and T_H17 cell responses

Allergy to dogs affects around ten percent of the population in developed countries. Immune therapy of allergic patients with dog allergen extracts has shown limited therapeutic benefit. Herein, we established a mouse model of dog allergy and tested the efficacy of a recombinant protein containing Can f 1, f 2, f 4 and f 6 as a sublingual immune therapy (SLIT). Repeated inhalation of dog extracts induced infiltration of the airways by T H 2 cells, eosinophils and goblet cells, reminiscent of the house dust mite (HDM) model of asthma. However, dog allergen extracts also induced robust T H 17 cell responses, which was associated with a high neutrophilic infiltration of the airways and promoted airway hyperresponsiveness more potently than HDM allergens. scRNA-Seq analysis of T helper cells responding to dog allergens identified several unique clusters with T H 17 cells being hallmarked by the expression of several receptors including IL-17RE. Analysis of T cell receptors also depicted a high frequency of clones that were shared between T H 17, T H 2 and suppressive Treg cells, indicative of the plasticity of T helper cells in this model. Importantly, prophylactic SLIT reduced airway hyperresponsiveness and type 2-mediated inflammation in this model supporting the use of recombinant allergens in immune therapy

Sublingual allergen immunotherapy with recombinant dog allergens prevents airway hyperresponsiveness in a model of asthma marked by vigorous T_H2 and T_H17 cell responses

AbstractAllergy to dogs affects around ten percent of the population in developed countries. Immune therapy of allergic patients with dog allergen extracts has shown limited therapeutic benefit. Herein, we established a mouse model of dog allergy and tested the efficacy of a recombinant protein containing Can f 1, f 2, f 4 and f 6 as a sublingual immune therapy (SLIT). Repeated inhalation of dog extracts induced infiltration of the airways by TH2 cells, eosinophils and goblet cells, reminiscent of the house dust mite (HDM) model of asthma. However, dog allergen extracts also induced robust TH17 cell responses, which was associated with a high neutrophilic infiltration of the airways and promoted airway hyperresponsiveness more potently than HDM allergens. scRNA-Seq analysis of T helper cells responding to dog allergens identified several unique clusters with TH17 cells being hallmarked by the expression of several receptors including IL-17RE. Analysis of T cell receptors also depicted a high frequency of clones that were shared between TH17, TH2 and suppressive Treg cells, indicative of the plasticity of T helper cells in this model. Importantly, prophylactic SLIT reduced airway hyperresponsiveness and type 2-mediated inflammation in this model supporting the use of recombinant allergens in immune therapy.</jats:p