RESUMEN
Background: 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. Methods: 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. Results: 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. Conclusions: 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.
Asunto(s)
Acuaporina 3 , Acuaporinas , Aspergillus fumigatus , Simulación por Computador , Imitación Molecular , Filogenia , Humanos , Aspergillus fumigatus/inmunología , Aspergillus fumigatus/metabolismo , Acuaporina 3/metabolismo , Acuaporinas/metabolismo , Acuaporinas/química , Acuaporinas/genética , Secuencia de Aminoácidos , Alérgenos/inmunología , Alérgenos/metabolismo , Hipersensibilidad/inmunología , Hipersensibilidad/microbiología , Modelos Moleculares , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/inmunologíaRESUMEN
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 the 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.
OBJETIVO: Realizar una evaluación in silico del posible mimetismo molecular entre las acuaporinas humanas, A. fumigatus y diversas fuentes alergénicas. MÉTODOS: Se compararon secuencias de aminoácidos de AQP3 humana y acuaporina de A. fumigatus mediante alineamientos múltiples con 25 acuaporinas de diversas fuentes alergénicas. Se ejecutaron análisis filogenéticos y modelos basados en homología, y el servidor ElliPro predijo regiones antigénicas preservadas en estructuras 3D. RESULTADOS: La identidad global entre las acuaporinas estudiadas fue del 32.6%, con una región local específica preservada en el 71.4%. Se formaron cinco clados monofiléticos (A-E), y el grupo B mostró la identidad más alta (95%), incluidas 6 acuaporinas de mamíferos, en particular AQP3. A. fumigatus aquaporin exhibió la mayor identidad con Malassezia sympodialis (35%). Se identificaron tres epítopos lineales y tres discontinuos en acuaporinas tanto humanas como de A. fumigatus. La desviación cuadrática media (RMSD) de las estructuras de acuaporinas superpuestas fue de 1,006. CONCLUSIÓN: La identificación de posibles epítopos lineales y conformacionales en AQP3 humano sugiere un probable mimetismo molecular con acuaporinas de A. fumigatus. La identidad alta en una región antigénica específica indica autorreactividad potencial y un sitio antigénico probable implicado en la reactividad cruzada. La validación mediante estudios in vitro e in vivo es desicivo para una mayor comprensión y confirmación.
