Cross-reactive epitopes and their role in food allergy

Allergenic cross-reactivity among food allergens complicates the diagnosis and management of food allergy. This can result in many patients being sensitized (having allergen-specific IgE) to foods without exhibiting clinical reactivity. Some food groups such as shellfish, fish, tree nuts, and peanuts have very high rates of cross-reactivity. In contrast, relatively low rates are noted for grains and milk, whereas many other food families have variable rates of cross-reactivity or are not well studied. Although classical cross-reactive carbohydrate determinants are clinically not relevant, α-Gal in red meat through tick bites can lead to severe reactions. Multiple sensitizations to tree nuts complicate the diagnosis and management of patients allergic to peanut and tree nut. This review discusses cross-reactive allergens and cross-reactive carbohydrate determinants in the major food groups, and where available, describes their B-cell and T-cell epitopes. The clinical relevance of these cross-reactive B-cell and T-cell epitopes is highlighted and their possible impact on allergen-specific immunotherapy for food allergy is discussed

Evaluation of oral immunotherapy efficacy and safety by maintenance dose dependency: A multicenter randomized study

Background Generally, oral immunotherapy (OIT) aims for daily administration. Recently, the efficacy of treatment with OIT at a low dose has been reported. However, the optimal dose and the evaluation of dose-dependent OIT outcome have not been described. Methods A multicenter, parallel, open-labeled, prospective, non-placebo controlled, randomized study enrolled 101 Japanese patients for treatment with OIT. We hypothesized that target dose OIT would induce short-term unresponsiveness (StU) earlier than reduced dose OIT. StU was defined as no response to 6200 mg whole egg, 3400 mg milk, and 2600 mg wheat protein, as evaluated by oral food challenge after 2-week ingestion cessation. To compare the two doses of OIT efficacy, the maximum ingestion doses during the maintenance phase of OIT were divided into 100%-dose or 25%-dose groups against their target StU dose, respectively. A total of 51 patients were assigned to the 100%-dose group [hen's egg (HE) = 26, cow's milk (CM) = 13, wheat = 12] and 50 to the 25%-dose group (HE = 25, CM = 13, wheat = 12). Primary outcome was established by comparing StU at 1 year. Secondary outcome was StU at 2 years and established by comparing allergic symptoms and immunological changes. Results The year 1 StU rates (%) for the 100%- and 25%-dose groups were 26.9 vs. 20.0 (HE), 7.7 vs. 15.4 (CM), and 50.0 vs. 16.7 (wheat), respectively. The year 2 StU rates were 30.8 vs. 36.0 (HE), 7.7 vs. 23.1 (CM), and 58.3 vs. 58.3 (wheat), respectively. There were no statistically significant differences in StU between years 1 and 2. The total allergic symptom rate in the 25%-dose group was lower than that in the 100%-dose group for egg, milk, and wheat. Antigen-specific IgE levels for egg-white, milk, and wheat decreased at 12 months. Conclusions Reduced maintenance dose of egg OIT showed similar therapeutic efficacy to the target dose. However, we were not able to clearly demonstrate the efficacy, particularly for milk and wheat. Reducing the maintenance dose for eggs, milk, and wheat may effectively lower the symptoms associated with their consumption compared to the target OIT dose. Furthermore, aggressive reduction of the maintenance dose might be important for milk and wheat, compared to the 25%-dose OIT

Risk and safety requirements for diagnostic and therapeutic procedures in allergology : World Allergy Organization Statement

Peer reviewe

Diagnosis of Food Allergy Based on Oral Food Challenge Test

Diagnosis of food allergy should be based on the observation of allergic symptoms after intake of the suspected food. The oral food challenge test (OFC) is the most reliable clinical procedure for diagnosing food allergy. The OFC is also applied for the diagnosis of tolerance of food allergy. The Japanese Society of Pediatric Allergy and Clinical Immunology issued the 'Japanese Pediatric Guideline for Oral Food Challenge Test in Food Allergy 2009' in April 2009, to provide information on a safe and standardized method for administering the OFC. This review focuses on the clinical applications and procedure for the OFC, based on the Japanese OFC guideline

Gamma-globulin Inhibits Superantigen-induced Lymphocyte Proliferation and Cytokine Production

Background: High-dose pooled human immunoglobulin (PHIG) treatment is sometimes effective in superantigen related inflammatory diseases, such as toxic shock syndrome and Kawasaki disease. Neutralizing antibody to superantigen might provide protection, but antigen independent immune regulation of PHIG is also a proposed mechanism. Methods: Staphylococcal enterotoxin B (SEB)-specific IgG antibody in PHIG products (Venoglobulin IH®) was detected by ELISA. The suppressive effect of PHIG or its fragments on proliferation and cytokine (IL-4 and IFN-γ) production from SEB-stimulated peripheral blood mononuclear cells was examined. Results: SEB-specific IgG was detected in PHIG products. PHIG (6.25-25 mg/ml) suppressed SEB-induced proliferation and cytokine production in a dose-dependent manner. Fab and F (ab’) 2 fractions of PHIG also suppressed the responses, but depletion of SEB-specific antibody from PHIG did not affect the inhibitory effects. The Fc fragment of PHIG also showed partial, but significant suppression. Conclusions: These data suggested the possibility that PHIG suppressed SEB-induced proliferation and cytokine production by some mechanisms independent of the presence of neutralizing antibody

Clinical Studies Using in Vivo Diagnostic Radiopharmaceuticals under the Clinical Research Law

The Japanese Ministry of Health, Labour and Welfare (JMHLW) introduced the Clinical Research Law1 in April 2018. Clinical studies to evaluate pharmacokinetics or the efficacy or safety of in vivo diagnostic radiopharmaceuticals have to be conducted under either the Clinical Research Law or the Japanese Good Clinical Practice (GCP) guidelines. The Clinical Research Law provides stricter regulation than does the current Ethical Guideline for clinical studies, and it allows the regulatory authority to issue orders to suspend or change clinical studies. Given that a clinical study may require the same amount of time, human resources and funding resources no matter which regulatory scheme is followed, clinical investigators need to bear in mind the objectives and funding support for the planned study when choosing which legislation to adhere to. This article reviews various factors that may help determine which of the recently introduced pieces of legislation is applicable in the planning of a particular clinical study. We also aim to establish approaches to identify the appropriate law and to enable non-clinical studies to move forward to the clinical study phase.1This review article was written before official release of the English translation of the Clinical Research Law in June 28 2018. Although the law is officially entitled the Clinical Trials Act in English, this review uses the terminology “the Clinical Research Law”