Inverse association between the molecular spreading of IgE to grass pollen and the IgE response to Dermatophagoides pteronyssinus among children with seasonal allergic rhinitis

Abstract

Background: Seasonal allergic rhinoconjunctivitis (SAR) is a worldwide health problem, especially in Westernized countries. Previous studies of the "Panallergens in Pediatrics" (PAN-PED) cohort found that molecular spreading (ie, the progressive increase in serum specific IgE antibody levels) of the IgE response to the grass pollen, Phleum pratense, molecules is directly associated with polysensitization to pollen in general.The research question is aimed at verifying whether this association can also be detected for non-pollen allergens, specifically Dermatophagoides pteronyssinnus (D.pt), to better understand the relationship between a perennial allergen (D.pt) and a seasonal allergen (Phleum pratense).To this end, our first objective was to analyze the biobank of the PAN-PED cohort serum by measuring the IgE levels to D.pt and its major recombinant molecules (Der p1, Der p2, Der p23); subsequently we investigated their correlation towards Phleum pratense IgE response, studying also the relationship between the molecular spreading of these 2 different allergens.

Methods: Among 1120 patients positive to Phleum pratense, 638 were also sensitized to D.pt. Patients underwent skin prick tests (SPT) for inhalant extracts, and their serum was tested for total IgE (tIgE), and sIgE to pollen and perennial allergens. Considering the molecular allergen detection through the component resolved diagnosis (CRD), out of 638 patients, 146 were further investigated by performing IgE tests of the 3 major D.pt. molecules: Der p1, Der p2, and Der p23.

Results: We found that a broader molecular response to Phleum pratense molecules, assessed by CRD, was associated with higher tIgE levels, polysensitization to pollens, and higher IgE levels to pollens, but also to lower IgE levels to D.pt and lower degree of sensitization to rDer p1, r Der p2, and rDer p23. In a multivariate linear model, the number of Phleum pratense molecules recognized by IgE was still inversely associated with the IgE level to D.pt extract.

Conclusions: The main finding of this study was the detection of an inverse association, never described in the literature, between the molecular spreading of the IgE response to Phleum pratense and the IgE response to D.pt. This led us to speculate on the etiopathogenetic hypothesis according to which, among the majority of pollen allergic patients, a strong and molecularly diversified IgE response may be limited to pollen allergens and may be preventing or contrasting the development of an equally strong and diversified IgE sensitization to D.pt molecules. The biological mechanisms underlying this phenomenon deserve to be investigated.

Keywords: Allergic rhinitis; Children; Dermatophagoides pteronyssinnus; Molecular spreading; Phleum pratense.

Fig. 1

The “Panallergens in Pediatrics” study population: flow chart with inclusion and exclusion criteria in the analysis of grass pollen allergic paients with or without IgE sensitization to house dust mites. D.pt: Dermatophagoides pteronyssinus Phl p1: Phleum pretense, IgE: Immunoglobulin IgE, Der p1, p2, p23: Dermatophagoides pteronyssinus.

Fig. 2

– IgE sensitization to Dermatophagoides pteronyssinnus and its major allergenic molecules, by number of Phleum pratense molecules recognized by IgE. For each subgroup and D.pt molecule, we calculated the percentage of positive outcome [Fig. 2a], geometric mean level [Fig. 2b], and the average specific activity of the serum IgE antibodies to Der p 1, Der p 2 and Der p 23 [Fig. 2c], the number of Dermatophagoides pteronyssinnus molecules recognized by sIgE, according to Phleum pratense ones [Fig. 2d]. The cumulative level of the IgE to these 3 antibodies [Fig. 2b] and the distribution of a molecular spreading index based on these 3 molecules only [Fig. 2a] are also shown. D.pt: Dermatophagoides pteronyssinus, Phl p1: Phleum pretense, IgE: Immunoglobulin IgE, Der p1, p2, p23: Dermatophagoides pteronyssinus.