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Background: In vitro immunoglobulin E (IgE) tests can be better standardized if based on molecules rather than extracts. However, singleplex screening tests for respiratory or food allergies are still based on extracts only. Target: To validate a novel singleplex IgE screening test for respiratory allergies, based on a mix of major allergenic molecules Der p 1, Der p 2, Fel d 1, Can f 1, Can f 2, Can f 3, Can f 5, Bet v 1, Phl p 1, and Art v 1 (Molecular SX01, NOVEOS, HYCOR, USA), and requiring only four microliters (μl) of serum. Methods: We examined six subsets of sera from participants of the German Multicenter Allergy Study (MAS) birth cohort enrolling 1314 newborns during 1990: (1) monosensitized (n = 58); (2) polysensitized (n = 24); (3) nonsensitized, with total IgE levels above (n = 24) or (4) below (n = 24) 300 kU/L; (5) sensitized to milk and/or egg but not to airborne allergens (n = 24); and (6) sera of children aged ≤5 years at their earliest IgE monosensitization to airborne allergens (n = 41). Sera were analyzed with the novel molecular SX01 test (NOVEOS) and with three categories of comparators: ImmunoCAP Phadiatop SX01, extracts, and molecules of D. pteronyssinus, cat, dog, grass, and birch. Sensitivity, specificity, positive and negative predictive values were calculated. Quantitative interrelationships were determined using Spearman's rank‐order correlation coefficient and Bland–Altmann plots. Results: The molecular SX01 test predicted the outcome of IgE tests based on molecules, extracts, or Phadiatop in 188 (96.4%), 171 (87.7%), and 171 (87.7%) of the 195 sera, respectively. Accordingly, sensitivity was 93.5%, 89.0%, and 82.4%, whereas specificity was 100%, 97.6%, and 96.1% when compared with molecular, extract, and Phadiatop tests, respectively. Inconsistent outcomes were largely confined to sera with IgE‐Ab levels around the cutoff value of 0.35 kU/L, except for 5/195 (2.5%) sera, containing high levels of IgE to Phl p 5 and/or Alt a 1 only. IgE levels measured by the molecular SX01 test and with IgE tests to molecules, extracts, and Phadiatop were highly correlated (rho 0.90; p <.001), (rho 0.87, p <.001), (rho 0.84, p <.001), respectively. The novel molecular SX01 test detected IgE‐Ab in 27/28 (sensitivity 96.4%) of the sera of preschool children at their earliest IgE sensitization to the same molecules. Discussion Our study validates the prototype of a novel category of IgE test, based on molecular mixes. The test's rather good precision and accuracy in early screening IgE sensitization to airborne allergens in German children may be further improved by adding a few other molecules, such as Phl p 5 and Alt a 1. [ABSTRACT FROM AUTHOR]

Background: There is growing interest both in testing IgE in nasal secretions (NS) and in molecular diagnosis of seasonal allergic rhinitis (SAR). Yet, the reliability of nasal IgE detection with the newest molecular assays has never been assessed in a large cohort of pollen allergic patients. Objective: To investigate with microarray technology and compare the repertoires of specific IgE (sIgE) antibodies in NS and sera of a large population of children and adults with SAR. Methods: Nasal secretions were collected with an absorbent device (Merocel 2000®, Medtronic) and a minimal dilution procedure from 90 children and 71 adults with SAR. Total IgE (tIgE) (ImmunoCAP, Thermo Fisher Scientific (TFS)) and sIgE antibodies against 112 allergen molecules (ISAC‐112, TFS) were measured in NS and serum. Results: Nasal sIgE was detectable in 68.3% of the patients. The detected nasal sIgE antibodies recognized airborne (88%), vegetable (10%), and animal food or other (<1%) allergen molecules. The prevalence and average levels of sIgE in NS and serum were highly interrelated at population level. A positive nasal sIgE antibody to a given molecule predicted the detection of the same antibody in the patient's serum with a specificity of 99.7% and a sensitivity of 40%. Conclusions: The concentration of sIgE is much lower in nasal secretions than in the serum. sIgE assays with very high analytical sensitivity and sampling methods with minimal dilution will be therefore needed to validate nasal secretions as alternative to serum in testing the sIgE repertoire. [ABSTRACT FROM AUTHOR]

The article discusses use of allergen‐specific immunotherapy (AIT) to cure allergic diseases by attacking their antigen‐specific immunologic mechanisms. Topics include better standardization of allergen products for diagnosis and therapy with molecular allergology, selection of molecules in order to identify genuine sensitization to the allergen, and producing recombinant molecules with hybrid technology.

Background Previous studies of serum total IgE (t-IgE) were not able to discriminate well-enough atopic from non-atopic subjects, that is, with or without serum-specific IgE antibodies to allergens. Objectives To model growth curves of the total IgE levels in children without atopic sensitization (hereafter defined as 'normal' t-IgE levels) and to test their usefulness in predicting atopic sensitization. Methods The German Multicentre Allergy Study ( MAS), a birth cohort with 1314 recruited newborns, began in 1990 and examined the participants until age 20 years. Total and specific IgE (t-IgE, s-IgE) were analyzed with a fluorescent enzyme immunoassay Immuno CAP ( TFS, Sweden) at ages 1, 2, 3, 5, 6, 7, 10, 13, and 20 years. Participants were classified as 'never atopic' if all their available serum samples had negative response (cutoff: <0.35 kUA/L) for s-IgE to the nine common foodborne and airborne allergenic extracts (milk, egg, soy, wheat, house dust mite, cat, dog, birch, and grass) tested in the MAS birth cohort. By contrast, participants were defined as atopic if they had, for at least at one available serum sample, s-IgE≥0.35 kUA/L to at least one allergenic extract tested. The evolution of t-IgE levels in the 'never atopic' children was described by growth curves, estimated by exploiting a quantile regression model. A 'reference' percentile, based on the t-IgE value measured at age 5 years, was assigned to each child with no IgE sensitization at that age. Upward deviations from the own 'reference' quantile of t-IgE in atopic and 'never atopic' children were calculated and a ROC analysis was used to identify the best cutoff point for predicting atopic sensitization. Results Overall, 1113 of 1314 children were included in this analysis. Of these, 469 were 'never atopic' and 644 atopic. Quantile trajectories of t-IgE levels in 'never atopic' subjects were stable from 5 years of age, increased to a plateau at age 10-13 years, and decreased slightly afterward. The onset of atopic s-IgE responses was characterized by an upward deviation of serum t-IgE levels from their 'reference' trajectory. T-IgE quantiles predicted the onset of atopy with high efficiency ( AUC>80%). ROC analysis showed that deviations from the t-IgE level 'reference' quantile above 0.32, 0.41, 0.42, 0.30, and 0.58 kU/L (log-units) at 6, 7, 10, 13, and 20 years of age, respectively, predicted an atopic sensitization. Conclusion The growth curves of 'normal' serum t-IgE concentrations were estimated in 'never atopic' children; for each individual who was non-atopic at 5 years of age a 'reference' quantile was identified that represented the individual's 'normal' level of t-IgE production. Upward deviations of observed t-IgE levels from the own 'reference' quantile, from 6 to 20 years of age, predicted at each year the occurrence of atopic sensitization. Clinical Implications The trajectory of t-IgE levels can be elaborated since age 5 years in non-atopic children. A child whose t-IgE levels are consistently higher than those predicted by his/her growth curve may have developed atopic sensitization. [ABSTRACT FROM AUTHOR]