Katsuhito Iikura

Clinical studies in oral allergen-specific immunotherapy: differences among allergens.

Oral immunotherapy (OIT) is a significant focus of treatment of food allergy. OIT appears to be effective in inducing desensitization, however, patients receiving OIT frequently developmild/moderate symptoms during the therapy. It has not been clearly established whether the clinical tolerance induced by OIT resembles natural tolerance. According to our data, the efficacy of OIT is different among food antigens, and it is comparatively difficult to achieve the clinical tolerance in milk OIT. Moreover, the definitive evidence of efficacy and safety with long-term therapy is limited. Further studies need to be offered to patients in clinical practice. Recently, novel treatments for food allergy, sublingual and epicutaneous immunotherapy, and combination treatment with an anti-IgE monoclonal antibody (omalizumab), have been examined in some studies. OIT combined with omalizumab increased the threshold doses of food without adverse reactions and may be of benefit in food allergy treatment. More studies are needed to demonstrate long-term safety and treatment benefits in a larger patient cohort.

Peripheral Blood Mononuclear Cells from Patients with Bronchial Asthma Show Impaired Innate Immune Responses to Rhinovirus in vitro

Background: Asthmatic patients have a higher susceptibility to rhinovirus (RV) infection, and impaired IFN-β and IFN-λ production has been demonstrated in bronchial epithelial cells from asthmatic adults upon exposure to RV. However, the mechanisms underlying the increased susceptibility of asthmatic patients to RV infection remain poorly understood. The present study aimed to elucidate the characteristics of the immune responses of asthmatic patients’ peripheral blood mononuclear cells (PBMCs) to RV exposure. Methods: PBMCs obtained from 3 different age groups (2–6 years: young-children group; 7–19 years: youth group; ≧20 years: adult group) of asthmatic patients and nonasthmatic control subjects were stimulated with RV-14 for 72 h. Healthy adults with a history of childhood asthma were also enrolled. The concentrations of IFN-α, IL-6, TNF-α, IL-10, and soluble Fas ligand (sFasL) in the culture supernatants were measured by ELISA. Results: When compared with age-matched control subjects, IFN-α production was significantly lower in the asthmatic youth group. IL-6, TNF-α, IL-10, and sFasL productions were significantly lower in both the asthmatic youth group and the adult group. Such impaired responses were not found in healthy adults with a history of childhood asthma. No significantly different responses were found between the asthmatics and controls in the young-children group, whereas young asthmatic children with persistent wheeze during a 2-year follow-up showed significantly lower IL-10 production than those without wheeze. Conclusions: These results imply the involvement of impaired production of both IFN-α and inflammatory cytokines seen in asthmatic patients’ PBMCs upon exposure to RV in the higher susceptibility of those patients to RV infection.

Oral immunotherapy initiation for multi-nut allergy: a case report.

Oral immunotherapy (OIT) has been reported to be effective for food allergy in recent years,1 but most studies on OIT have focused on a single antigen. Begin et al. first reported the use of OIT using peanuts and another allergen simultaneously, which was feasible and relatively safe.2 The purpose of this study was to evaluate the safety and efficacy of multi-nut OIT initiation for a patient with multi-nut allergy. We enrolled a 22-year-old man who had peanut, cashew nut, andwalnut allergies. He experienced face swelling after eating peanuts at the age of one. He and his mother tried to eliminate peanuts and other nuts completely; however, he occasionally ingested nuts accidentally. He had conjunctival erythema, lip swelling, and a cough after peanut ingestion at the age of 17 and generalized flushing, vomiting, and breathing difficulty after cashew nut ingestion at the age of 21. He was initially checked for food-specific IgE (sIgE) and component-resolved diagnostics (CRD) using the ImmunoCAP assay system (Thermo Fisher Scientific, Uppsala, Sweden). Food sIgE (kU/l) was 11.6 for peanut, 3.87 for cashew nut, 6.08 for walnut, 5.92 for pistachio, 2.22 for macadamia nut, and <0.10 for almond and hazel nuts. CRD was 0.24 for Ara h 1, 13.6 for Ara h 2, 7.34 for Ana o 3, <0.10 for Ara h 3, 8, and 9, Jug r 1 and 3, Bet v 1 and 2, Pru p 3, and Gly m 4, 5, and 6. Open oral food challenge of 0.5 g of peanut or 3.0 g of each nut was conducted before OIT. Peanut was administered at 60-min intervals as follows: 1/4 and 3/4. Each nut was administered at 30-min intervals as follows: 1/8, 3/ 8, and 4/8. He reacted to 0.5 g of peanut, 1.1 g of cashew nut, and 3.0 g of walnut. He tolerated pistachio, macadamia nut, almond, and hazel nut. He received OIT using peanut, cashew nut, and walnut simultaneously. From the day of admission, he took loratadine (10 mg) before nut intake. On the day of admission, a double-blind, placebo-controlled food challenge (DBPCFC) was performed. The challenge food was made by mixing equal amounts of the three nuts. From the second to fourth day in the hospital, he ingested mixed nut powder, which contained equal amounts of the three nuts, twice a day. During his stay, we adjusted the amount so that he would not experience severe symptoms at home. After discharge, he took the same amount once a day after taking loratadine. We investigated the severity of symptoms for safety and changes in symptom occurrence and food sIgE for efficacy. This study was approved by the Sagamihara National Hospital Ethics Committee