Trial Of Oral Immunotherapy Research Articles

Regulatory T-cell Patterns and Cytokine Profiles Suggest the Development of Tolerance in Patients Undergoing Peanut Oral Immunotherapy (OIT)

RATIONALE: To better understand the possible mechanisms of desensitization and tolerance in patients undergoing OIT, cytokine profiles and regulatory T-cells were evaluated in patients enrolled in an open peanut OIT trial.

Is interstitial cystitis an allergic disorder?

In our recent clinical trial, the addition of omalizumab to oral immunotherapy (OIT) for milk allergy improved safety, but no significant clinical benefit was detected.We sought to investigate mechanisms by which omalizumab modulates immunity in the context of OIT and to identify baseline biomarkers that predict subgroups of patients most likely to benefit from omalizumab.Blood was obtained at baseline and multiple time points during a placebo-controlled trial of OIT for milk allergy in which subjects were randomized to receive omalizumab or placebo. Immunologic outcomes included measurement of basophil CD63 expression and histamine release and casein-specific CD4+ regulatory T-cell proliferation. Biomarkers were analyzed in relationship to measurements of safety and efficacy.Milk-induced basophil CD63 expression was transiently reduced in whole blood samples from both omalizumab- and placebo-treated subjects. However, IgE-dependent histamine release increased in washed cell preparations from omalizumab- but not placebo-treated subjects. No increase in regulatory T-cell frequency was evident in either group. Subjects with lower rates of adverse reactions, regardless of arm, experienced better clinical outcomes. Pre-OIT basophil reactivity positively associated with occurrence of symptoms during OIT, whereas the baseline milk IgE/total IgE ratio correlated with the likelihood of achieving sustained unresponsiveness. A combination of baseline basophil and serologic biomarkers defined a subset of patients in which adjunctive therapy with omalizumab was associated with attainment of sustained unresponsiveness and a reduction in adverse reactions.Combining omalizumab therapy with milk OIT led to distinct alterations in basophil reactivity but not T-cell responses. Baseline biomarkers can identify subjects most likely to benefit from adjunctive therapy with omalizumab.

A three‐year double‐blind placebo‐controlled study with specific oral immunotherapy to Dermatophagoides: evidence of safety and efficacy in paediatric patients

Very few double-blind trials of oral immunotherapy have been reported. The majority of these have been performed with pollen extracts and the results have often been equivocal. The major weaknesses of these studies have been the short periods of the trials, the low doses of allergen employed and inadequate evaluation of efficacy. The present study has involved a placebo-controlled double-blind trial of oral immunotherapy for three years with Dermatophagoides pteronyssinus at relatively high doses in 18 paediatric patients. Throughout the trial clinical parameters (symptom and medication scores) and immunological parameters (specific IgE, IgG1 and IgG4 levels) were monitored in order to assess the safety and efficacy of the treatment. The treatment was well tolerated by all patients and no side-effects were experienced. Clinical improvement was evident after the second year of therapy and this was confirmed by a significant reduction in conjunctival reactivity assessed by a specific conjunctival provocation test. In addition, there were significant changes in the immunological parameters with a reduction in specific IgE and increased levels of IgG4 and IgG1, results in keeping with previous studies of oral and subcutaneous immunotherapy. Although the results do not provide an explanation of the basis of successful oral immunotherapy, they clearly demonstrate the efficacy and safety of the treatment and suggest that it may be a useful and more acceptable alternative for patients than the traditional subcutaneous immunotherapy.

Specific IgE, IgG, and IgA antibody response to oral immunotherapy in birch pollinosis

Thirty-nine patients with birch pollinosis participated in a double-blind, placebo-controlled trial of oral immunotherapy (OIT) for 18 months. They were treated with increasing doses of freeze-dried birch-pollen antigens for 16 months, reaching a cumulative dose of 280 × 10 6 biologic units. This is about 200 times more than the dose used in conventional subcutaneous immunotherapy (IT). In the placebo-treated group, but not in the actively treated group, there was a rise in postseasonal birch-specific IgE antibody levels. A significant decline in postseasonal values after 1 year of treatment was recorded in the actively treated, but not in the placebo-treated, group. Compared to the placebo treatment, there was a significant rise in birch-specific IgG antibodies in patients administered active treatment; however, the rise was less than that usually observed during subcutaneous IT. No significant change in birch-specific serum IgA was found in either group. The changes in IgE and IgG antibody levels demonstrate that OIT affects the immune system. This supports our recent findings that OIT demonstrates a beneficial effect in the treatment of birch pollinosis in adults. But, as with subcutaneous IT, there was no clear relationship between antibody response and clinical findings in the patients. The underlying mechanisms responsible for the relief of symptoms thus remain unknown.