Immunoglobulin A and immunoglobulin G antibodies against ß-lactoglobulin and gliadin at age 1 associate with immunoglobulin E sensitization at age 6.

BACKGROUND: Serum immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies against wheat gliadin and cow's milk ß-lactoglobulin (BLG) are considered markers of gut permeability and inflammation which modulate the development of mucosal tolerance. Living on a farm has been shown to decrease allergies in children. Our aim was to study whether farm environment affected mucosal tolerance, immunoglobulin E (IgE) sensitization, or allergic diseases. METHODS: The PASTURE birth cohort study was conducted in Finland, France, Germany, Austria, and Switzerland. At age 1, we measured serum IgA and IgG against wheat gliadin (N = 636) and cow's milk BLG (N = 639) using ELISA. Serum-specific IgE was measured at ages 1 and 6 (N = 459). Data on environmental factors and allergic diseases were collected by questionnaires. Discrete time hazard and multivariate logistic regression models were used for analyses. RESULTS: Increased IgA or IgG antibodies against BLG at age 1 increased the risk of sensitization to at least one of the measured allergens or food allergens at age 6. Increased IgG against gliadin at age 1 increased the risk of sensitization to any, at least one inhalant, or at least one food allergen at age 6. Early exposure to cow's milk formula associated with increased IgA or IgG against BLG. No association with farming or clinical allergy was found. CONCLUSIONS: Increased IgA or IgG against BLG or gliadin at age 1 was associated with IgE sensitization at age 6. We suggest that an enhanced antibody response to food antigens reflects mucosal tolerance aberrancies, e.g., altered microbiota and/or increased gut permeability, which is later seen as sensitization to allergens.

Precision medicine allergy immunoassay methods for assessing immunoglobulin E sensitization to aeroallergen molecules.

Molecular-based allergy diagnosis for the in vitro assessment of a patient immunoglobulin E (IgE) sensitization profile at the molecular level uses allergen molecules (also referred to as allergen components), which may be well-defined, highly purified, natural allergen components or recombinant allergens. Modern immunoassay methods used for the detection of specific IgE against aeroallergen components are either singleplex (such as the fluorescence enzyme immunoassay with capsulated cellulose polymer solid-phase coupled allergens, the enzyme-enhanced chemiluminescence immunoassay and the reversed enzyme allergosorbent test, with liquid-phase allergens), multiparameter (such as the line blot immunoassay for defined partial allergen diagnostics with allergen components coating membrane strips) or multiplex (such as the microarray-based immunoassay on immuno solid-phase allergen chip, and the two new multiplex nanotechnology-based immunoassays: the patient-friendly allergen nano-bead array, and the macroarray nanotechnology-based immunoassay used as a molecular allergy explorer). The precision medicine diagnostic work-up may be organized as an integrated "U-shape" approach, with a "top-down" approach (from symptoms to molecules) and a "bottom-up" approach (from molecules to clinical implications), as needed in selected patients. The comprehensive and accurate IgE sensitization molecular profiling, with identification of the relevant allergens, is indicated within the framework of a detailed patient's clinical history to distinguish genuine IgE sensitization from sensitization due to cross-reactivity (especially in polysensitized patients), to assess unclear symptoms and unsatisfactory response to treatment, to reveal unexpected sensitizations, and to improve assessment of severity and risk aspects in some patients. Practical approaches, such as anamnesis molecular thinking, laboratory molecular thinking and postmolecular anamnesis, are sometimes applied. The component-resolved diagnosis of the specific IgE repertoire has a key impact on optimal decisions making for prophylactic and specific immunotherapeutic strategies tailored for the individual patient.