Clinical & Experimental Allergy Reviews最新文献

The oral mucosa is well known to be rich in dendritic cells (DCs), and the cervical lymph nodes (CLNs) are the draining lymph nodes for the oral mucosa. DCs play a crucial role in the induction of primary T cell-dependent immune responses. Upon uptake of antigens on the oral mucosal surface, immature DCs in the oral mucosa are thought to migrate to the regional CLNs. The oral mucosa is a potential route for vaccine administration. We examined the efficacy and some candidate biomarkers of the clinical responses to sublingual immunotherapy (SLIT) with a cedar pollen extract against cedar pollinosis. We found that Lactobacillus KW3110 administered sublingually migrated to the CLNs, and was effective for decreasing the IgE production and nasal symptoms induced by antigen provocation. Through simultaneous stimulation with antigen, improved efficacy of SLIT may be achieved by an adjuvant with oral mucosal administration of Lactobacillus KW3110.

The characteristics and natural course of gastrointestinal (GI) allergies, which mainly affect infants and young children, are not fully determined. We investigated the nature of neonatal and infantile GI allergies and the efficacy of slow oral immunotherapy in patients with persistent symptoms. We observed 12 patients (five boys, seven girls) aged at first presentation from 0 days to 8 months after birth. Detailed interviews, peripheral blood eosinophil counts, antigen-specific IgE antibody levels, antigen-specific lymphocyte stimulation tests (LSTs), stool occult blood eosinophil counts and skin tests were performed in combination with milk elimination tests. Five patients underwent an intestinal mucosal biopsy. Provocation testing was used to assess tolerance acquisition. The only clinical symptom in six patients was bloody stool, while vomiting, fever, poor weight gain or hepatic dysfunction developed in six patients. Milk-specific LSTs were positive in 10 of 11 cases tested. Lower GI endoscopy showed large numbers of infiltrating eosinophils in four of five patients with an intestinal mucosal biopsy. Provocation tests to confirm tolerance acquisition were performed in three patients. Interestingly, one patient suffered IgE-mediated GI anaphylaxis during the provocation test. One patient had a sustained high LST index, and elimination of dairy milk products was continued. At 4 years of age, she underwent an oral challenge test. On ingestion of 5 mL of milk, she exhibited fever, loose stool, poor appearance and increased white blood cell counts, which was considered a positive provocation test. Therefore, slow oral immunotherapy was started using 1/20 of the threshold dose, with fat intake at least four times per week. This was steadily increased by 20% over 2 weeks without inducing symptoms. The characteristics of neonatal and infantile GI allergies are diverse, and they generally remit spontaneously. However, patients who do not develop tolerance may be suitable choices for oral immunotherapy.

Allergic rhinitis has the greatest prevalence of any respiratory disease and affects about 20% of the population in North America and Europe. There is an increasing need for allergen challenge systems to test anti-allergic drugs under well-controlled conditions. The allergen challenge chamber (ACC) is a room that enables reproducible challenges with controlled levels of inhalant allergens, temperature and humidity for several hours. ACCs have been used in Europe, North America and Japan to evaluate symptomatic and anti-inflammatory medications for the treatment of allergic rhinitis. This review summarizes the experience with a typical ACC in Germany, the Fraunhofer Challenge Chamber, and describes the stability and reproducibility of the allergen exposure in the chamber. It further provides data for the specificity and reproducibility of clinical read-out parameters, such as nasal symptom scores, nasal flow rates and nasal secretions, as well as of nasal biomarkers obtained in different validation studies. Typical study designs for testing the acute and prophylactic treatment effects of anti-allergic substances are discussed. Regulatory authorities, such as the FDA and EMA, recommend the use of ACCs in drug development to evaluate the optimal dose and onset of action during early clinical development. In combination with natural-exposure Phase III studies, they provide supportive evidence of superiority over placebo as an additional pharmacodynamic assessment tool. In particular, ACC studies may be of additional value in the clinical development of immunotherapy, because the variability of natural allergen exposure hampers the demonstration of efficacy in clinical trials.

Mucosal vaccines are considered to be a promising strategy for preventing upper airway infections. As immunization routes to induce mucosal immune responses, oral, intranasal and sublingual immunizations have been proposed for clinical application. Recently, it was reported that transcutaneous immunization (TC) is also capable of inducing mucosal as well as systemic immune responses. However, it remains unclear which route is most effective for inducing mucosal immune responses in upper respiratory airways. In this study, the mucosal immune responses against phosphorylcholine (PC), a structural component of a wide variety of Gram-positive and -negative bacteria, were investigated after intranasal, sublingual, or TC. Female BALB/c mice were immunized intranasally, sublingually, or transcutaneously with PC and cholera toxin. For the TC, the dorsal region was shaved and a cotton patch soaked with the antigen was attached. Nasal wash, saliva and serum samples were collected at 7 days after the final immunization, and examined for their PC-specific antibody activities using ELISA. Phosphorylcholine-specific antibodies in serum and PC-specific IgA in nasal washes and saliva were detected in mice after intranasal and sublingual immunization with PC. Although salivary IgA was higher following intranasal immunization, nasal wash IgA was significantly higher after sublingual immunization. Furthermore, significantly increased IgA in vaginal washes and remarkably decreased serum IgE production were observed after sublingual immunization. TC increased PC-specific IgA in faecal samples, but not in saliva. The PC antigen can induce mucosal as well as systemic immune responses when administered via intranasal, sublingual and transcutaneous routes. Sublingual immunization is superior to intranasal immunization in terms of safety for inducing mucosal immune responses. Although TC might be an alternative way to induce mucosal immune responses, further investigation is needed for its application as a vaccine route to prevent upper airway infection.