IgE recognition patterns of profilin, PR-10, and tropomyosin panallergens tested in 3,113 allergic patients by allergen microarray-based technology

Abstract

Background: IgE recognition of panallergens having highly conserved sequence regions, structure, and function and shared by inhalant and food allergen sources is often observed.

Methods: We evaluated the IgE recognition profile of profilins (Bet v 2, Cyn d 12, Hel a 2, Hev b 8, Mer a 1, Ole e 2, Par j 3, Phl p 12, Pho d 2), PR-10 proteins (Aln g 1, Api g 1, Bet v 1.0101, Bet v 1.0401, Cor a 1, Dau c 1 and Mal d 1.0108) and tropomyosins (Ani s 3, Der p 10, Hel as 1, Pen i 1, Pen m 1, Per a 7) using the Immuno-Solid phase Allergen Chip (ISAC) microarray system. The three panallergen groups were well represented among the allergenic molecules immobilized on the ISAC. Moreover, they are distributed in several taxonomical allergenic sources, either close or distant, and have a route of exposure being either inhalation or ingestion.

Results: 3,113 individuals (49.9% female) were selected on the basis of their reactivity to profilins, PR-10 or tropomyosins. 1,521 (48.8%) patients were reactive to profilins (77.6% Mer a 1 IgE(+)), 1,420 (45.6%) to PR-10 (92.5% Bet v 1 IgE(+)) and 632 (20.3%) to tropomyosins (68% Der p 10 IgE(+)). A significant direct relationship between different representative molecules within each group of panallergens was found. 2,688 patients (86.4%) recognized only one out of the three distinct groups of molecules as confirmed also by hierarchical clustering analysis.

Conclusions: Unless exposed to most of the allergens in the same or related allergenic sources, a preferential IgE response to distinct panallergens has been recorded. Allergen microarray IgE testing increases our knowledge of the IgE immune response and related epidemiological features within and between homologous molecules better describing the patients' immunological phenotypes.

Figure 1. Age group distribution of the ISAC IgE panallergens-reactive population; n = 3,113.

Black bars: Total 23,077 original allergic population; White Bars: Total 3,113 panallergens allergic population; Dark grey bars: PR-10; Hatched bars: Profilin; Light grey bars: Tropomyosin.

Figure 2. Venn diagram comparative representations of the IgE reactivity distributions.

Panel A: Venn diagram of IgE reactivity distributions of the three panallergen groups, profilins, PR-10, and tropomyosin (n = 3,113); Panel B: Venn diagram of IgE reactivity distributions of genuine inhalant allergens Phl p 1, Der p 1, and including Bet v 1 when considered as a marker of genuine pollen sensitization; Panel C: Venn diagram of IgE reactivity distributions of exclusive genuine inhalant allergens Phl p 1, Der p 1, and Par j 2; Panel D: Statistical comparative evaluations of concurrent IgE reactivity to 1, 2, 3, or 2 and 3 groups in Venn diagrams shown in panel A (dark grey hatched bars), panel B (light grey horizontal line bars), panel C (white vertical line bars).

Figure 3. Bivariate analysis of reciprocal relationships of IgE to profilin, PR-10, and tropomyosin panallergens.

The number of IgE reactive subjects and the Pearson coefficient are shown for paired allergens within the three panallergen groups. Pearson r values are reported below. Data were statistically significant in all cases (p<0.001). Panel A: Profilins; Panel B: PR-10; Panel C: Tropomyosins.

Figure 4. Supervised two-way hierarchical clustering analysis of panallergen IgE values.

Subjects had at least one IgE-positive result to the panallergens under study. Allergens are reported on the y-axis, subjects on the x-axis. Black to dark red scale corresponds to IgE values from negative to strongly positive. Further explanations are in the ‘Methods’ section. Panel A: Profilins; Panel B: PR-10; Panel C: Tropomyosins.