Evolution of allergen sensitization patterns in children with preschool wheeze and asthma of the ALLIANCE cohort

<bold>Background:</bold> Sensitization patterns evolve and change over time in patients with allergy and asthma. <bold>Methods:</bold> SIgE against 36 aero- and food allergens were measured by Euroline(T) in children from the ALLIANCE cohort (135 with preschool wheeze (W), 254 with asthma (A) and 84 healthy controls (HC). Clustering by k-modes was performed at baseline and after 4-5 years of follow-up (W: 56 , A: 150). <bold>Results:</bold> We identified 6 distinct clusters of allergen patterns: house dust mite (Hdm, n= 121), alternaria (Alt, n= 17), Hdm and grass (Hdm+g, n=68), polysensitization with aeroallergens (poly1, n= 68), polysensitization with aero- and food allergens (poly2, n= 30) and a “mixed group” (mixed, n=169). All clusters were seen in asthmaticPatients of the “mixed” cluster were overall younger compared to the Hdm cluster and the Hdm+grass cluster (8,1 years SD 4,6 vs. 9,6 yrs SD 4,2 vs. 11,1 years SD 4,1 respectively; p<0.0001) and had lower blood eosinophil levels compared to all other clusters except “alternaria” (357/µl SD 295 vs. 560/µl SD 419, p< 0,001). Patients with polysensitization usually remained in the poly 1+2 cluster. Patients in the Hdm cluster (63,8%) and the mixed cluster (57,4%) acquired further sensitizations over time. At a molecular level, these patients had significantly increased levels of Der f2 (mean sIgE 13,3 ISU/l versus 24 ISU/l, p=0,035) and Phl p1 (mean sIgE 0,19 ISU/l versus 0,9 ISU/l, p=0,007). <bold>Conclusion:</bold> Unsupervised analysis of specific IgE levels reveals clusters with distinct longitudinal behavior. On a molecular level, sensitization against certain allergens are associated with increasing sensitization over time and could help identify patients at risk.