D2.13 - Structural Homology of Alt a 1 and Phl p 2 Suggests an explanation for coincidence of Grass and Alternaria Allergies

Allergy to grass pollen is frequently linked to sensitization to fungal spores, particularly Alternaria, traditionally attributed to their coinciding summer peaks in pollination and sporulation. However, our study proposes an alternative explanation, suggesting structural similarity between the key Alternaria allergen Alt a 1 and the genuine grass allergen Phl p 2.

We analyzed a dataset of 6169 individuals with grass sensitization from 17 Ukrainian regions, aged 1–89 years. Agglomerative clustering was applied to identify allergen clusters driving simultaneous sensitization in grass-allergic patients. Bayesian modeling established a hierarchy of molecular allergens based on their sensitization potential. Additionally, a phylogenetic tree was constructed using amino acid sequences of tested allergens (MAFFT multiple alignment, qtree algorithm, WAG evolution model) to explore structural relationships.

Clustering revealed that Alt a 1 and Phl p 2 belong to the same cluster. Bayesian analysis indicated that Alt a 1 may dominate in triggering immune responses within this pair, overshadowing Phl p 2. The phylogenetic tree further confirmed the structural homology between these proteins, suggesting potential cross-reactivity, aligning with the hypothesis of convergent evolution due to Alternaria’s parasitic interaction with grasses.

Our findings challenge the solely temporal explanation of grass-Alternaria co-sensitization, highlighting a structural and phylogenetic basis for cross-reactivity between Alt a 1 and Phl p 2. This discovery underscores the need to reconsider diagnostic and therapeutic approaches for patients with combined grass and fungal allergies, emphasizing Alt a 1’s dominant role in immune activation.