Exploratory immunogenicity outcomes of peanut oral immunotherapy: Findings from the PALISADE trial.

BACKGROUND: Immunoglobulin E (IgE) and immunoglobulin G4 (IgG4) to peanut and its components may influence the clinical reactivity to peanut. Allergen-specific immunotherapy is known for modifying both IgE and IgG4. Peanut oral immunotherapy may influence these serological parameters. METHODS: Exploratory analyses of serological data from participants receiving peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) and placebo in the double-blind, randomized, phase 3 PALISADE trial were conducted to evaluate potential relationships between peanut-specific and peanut component-specific (Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 8, and Ara h 9) IgE and IgG4 levels and clinical outcomes. RESULTS: A total of 269 participants (PTAH, n = 202; placebo, n = 67) were analyzed. No relationship was observed between specific IgE and IgG4 levels at screening and maximum tolerated peanut protein dose during screening or response status during exit double-blind placebo-controlled food challenge (DBPCFC). In PTAH-treated participants, no relationship was observed between IgE and IgG4 levels at screening and maximum symptom severity during exit DBPCFC. Postscreening ratios (ie, postscreening/screening) in the PTAH group were significant at the end of updosing and exit visit for most components. Postscreening changes in specific IgE levels were more pronounced with PTAH versus placebo for most components. CONCLUSIONS: Specific IgE and IgG4 levels at screening are not correlated with screening or exit DBPCFC results, and are not predictive of clinical response to PTAH. Peanut (Arachis hypogaea) allergen powder-dnfp contains the relevant and immunodominant allergens, inducing immunological changes with the treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02635776.

History and Utility of Specific IgE Cutoff Levels: What is the Relevance for Allergy Diagnosis?

Allergy is defined clinically, by symptoms on allergen exposure. A patient is considered sensitized when allergen-specific IgE (sIgE) antibody can be detected in serum or plasma or a skin test result is positive, even if no clinical reaction has been experienced. Sensitization should be regarded as a requisite and risk factor for allergy but is not synonymous with an allergy diagnosis. To provide a correct allergy diagnosis, test results regarding allergen-sIgE must always be considered in view of the patient's case history and clinical observations. Correct assessment of a patient's sensitization to specific allergens relies on the use of accurate and quantitative methods for detection of sIgE antibodies. The evolution of sIgE immunoassays toward higher analytical performance and the use of different cutoff levels in the interpretation of test results sometimes cause confusion. Earlier versions of sIgE assays offered a limit of quantitation of 0.35 kilounits of sIgE per liter (kUA/L), which also became an established cutoff level for a positive test result in the clinical use of the assays. Current sIgE assays are capable of reliably measuring sIgE levels as low as 0.1 kUA/L and can thereby demonstrate sensitization in cases in which previous assays could not. When the outcome of sIgE test results is evaluated, it is critically important to distinguish between the analytical data as such and their clinical interpretation. Even though sIgE may be present in the absence of symptoms of allergy, available information suggests that sIgE concentrations between 0.1 kUA/L and 0.35 kUA/L may be clinically relevant in some individuals, not least among children, although this should be further evaluated for various allergies. Moreover, it is becoming widely adopted that nondichotomous interpretation of sIgE levels may offer a diagnostic benefit compared with using a predefined cutoff level.

The ImmunoCAP Rapid Wheeze/Rhinitis Child test is useful in the initial allergy diagnosis of children with respiratory symptoms.

Recurrent upper or lower respiratory symptoms, possibly allergy-related, are very frequent in childhood. It is therefore important that physicians involved in the primary care of these children have an accurate initial diagnostic tool available. In this study, we investigated the value of an in vitro diagnostic device testing 10 common allergens, the ImmunoCAP Rapid Wheeze/Rhinitis Child, for the primary evaluation of allergy. Children with non-infectious upper or lower respiratory symptoms possibly related to allergy were recruited in the primary health care setting of private practices of physician trained in immunology/allergology. The investigators carried out their usual diagnostic work-up including IgE tests, and the ImmunoCAP Rapid test was performed with capillary whole blood in a blinded way to the investigator. The investigators' conclusions on major triggering allergens were compared to the ImmunoCAP Rapid test results. In the whole patient population (n = 185), the sensitivity of the ImmunoCAP Rapid test for unveiling allergic disease was 92% (95% CI: 86-96%) and the specificity 97% (95% CI: 86-100%). Current guidelines for allergy diagnosis suggest screening children with recurrent, moderate/severe diseases for allergies. For children with asthma falling into these categories, sensitivity was 100% (95% CI: 88-100%) and specificity 100% (95% CI: 69-100%); for children with moderate and severe rhinitis sensitivity was 93% (95% CI: 86-97%) and the specificity 100% (95% CI: 79-100%). The ImmunoCAP Rapid test is an accurate test, in particular with regard to high specificity, for diagnosing allergy in children with recurrent respiratory diseases in primary care settings.

The use of serum-specific IgE measurements for the diagnosis of peanut, tree nut, and seed allergy.

BACKGROUND: The gold standard for diagnosing food allergy is the double-blind, placebo-controlled food challenge. Diagnostic food-specific IgE levels might assist in diagnosing food allergies and circumventing the need for food challenges. OBJECTIVES: The purpose of this study was to determine the utility of food-specific IgE measurements for identifying symptomatic peanut, tree nut, and seed allergies and to augment what is known about the relationships among these foods. METHODS: Patients referred for suspected peanut or tree nut allergies answered a questionnaire about their perceived food allergies. Allergen-specific diagnoses were based on questionnaire, medical history, and, when relevant, skin prick tests and serum specific IgE levels. Sera from the patients were analyzed for specific IgE antibodies to peanuts, tree nuts, and seeds by using ImmunoCAP Specific IgE (Phadia, Inc, Uppsala, Sweden). RESULTS: Three hundred twenty-four patients (61% male; median age, 6.1 years; range, 0.2-40.2 years) were evaluated. The patients were highly atopic (57% with atopic dermatitis and 58% with asthma). The majority of patients with peanut allergy were sensitized to tree nuts (86%), and 34% had documented clinical allergy. The relationship between diagnosis and allergen-specific IgE levels were estimated by using logistic regression. Diagnostic decision points are suggested for peanut and walnut. Probability curves were drawn for peanut, sesame, and several tree nuts. High correlations were found between cashew and pistachio and between pecan and walnut. CONCLUSIONS: Quantification of food-specific IgE is a valuable tool that will aid in the diagnosis of symptomatic food allergy and might decrease the need for double-blind, placebo-controlled food challenges.