In silico analysis of molecular mimicry between human aquaporin 3, Aspergillus fumigatus aquaporin and aquaporins from allergic sources.

Background: Atopic dermatitis (AD) profoundly impacts quality of life as a chronic inflammatory skin disease. Allergen exposure triggers specific IgE antibodies, initiating allergy symptoms. Cross-reactivity, linked to auto-IgE responses, potentially influences AD severity. Exploring new allergens and self-autoantigens, like Aspergillus fumigatus, enhances knowledge of AD triggers. Our focus was on analyzing molecular mimicry between human AQP3 and A. fumigatus aquaporin, alongside various allergenic sources. Objective: Conduct an in silico assessment of potential molecular mimicry between human aquaporins, A. fumigatus, and diverse allergenic sources. Methods: Amino acid sequences of human AQP3 and A. fumigatus aquaporin were compared through multiple alignments with 25 aquaporins from diverse allergenic sources. Phylogenetic analysis and homology-based modeling were executed, and ElliPro server predicted conserved antigenic regions on 3D structures. Results: Global identity among studied aquaporins was 32.6%, with a specific conserved local region at 71.4%. Five monophyletic clades (A-E) were formed, and Group B displayed the highest identity (95%), including 6 mammalian aquaporins, notably AQP3. A. fumigatus aquaporin exhibited the highest identity with Malassezia sympodialis (35%). Three linear and three discontinuous epitopes were identified in both human and A. fumigatus aquaporins. The Root Mean Square Deviation (RMSD) from overlapping aquaporin structures was 1.006. Conclusion: Identification of potential linear and conformational epitopes on human AQP3 suggests likely molecular mimicry with A. fumigatus aquaporins. High identity in a specific antigenic region indicates potential autoreactivity and a probable antigenic site involved in cross-reactivity. Validation through in vitro and in vivo studies is essential for further understanding and confirmation.