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

## TL;DR

This study explores how human and fungal aquaporins might trigger allergic reactions through molecular mimicry, potentially worsening atopic dermatitis.

## Contribution

The paper identifies conserved antigenic regions and potential epitopes in aquaporins that suggest molecular mimicry between human and fungal sources.

## Key findings

- Aquaporins from human and allergenic sources share conserved antigenic regions with up to 71.4% local identity.
- Human AQP3 and A. fumigatus aquaporins share similar linear and conformational epitopes, suggesting molecular mimicry.
- Aquaporins were grouped into five clades, with mammalian aquaporins showing the highest identity (95%).

## Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin condition that has a significant impact on quality of life. The immune response and allergy symptoms in AD are triggered by the recognition of specific allergens by IgE antibodies. Cross-reactivity can lead to auto-IgE responses, potentially worsening AD symptoms. Our research aimed to enhance our understanding of allergenic sources, including A. fumigatus, and their role in AD. We focused on molecular mimicry between human AQP3 and A. fumigatus aquaporin.

In our in-silico analysis, we compared the amino acid sequences of human aquaporin 3 (AQP3) and A. fumigatus aquaporin with 25 aquaporins from various allergenic sources, sourced from the UniProt and NCBI databases. Phylogenetic relationship analysis and homology-based modeling were conducted. We identified conserved antigenic regions located within the 3D structures.

The global identity levels among the studied aquaporins averaged 32.6%. One antigenic site exhibited a remarkable local region, with a conserved identity of 71.4%. We categorized the aquaporins into five monophyletic clades (A–E), with group B showing the highest identity (95%), including six mammalian aquaporins, including AQP3. When comparing
A. fumigatus aquaporins, the highest identity was observed with
Malassezia sympodialis at 35%. Both human and A. fumigatus aquaporins have three linear and three discontinuous epitopes.

We identified potential linear and conformational epitopes of AQP3, indicating a possible molecular mimicry between humans and
A. fumigatus aquaporins. This suggests autoreactivity and potential cross-reactivity, although further validation using in vitro and in vivo experiments is required.