Περίληψη:
Background
The mechanisms explaining the co-existence of asthma, eczema and
rhinitis (allergic multimorbidity) are largely unknown. We investigated
the mechanisms underlying multimorbidity between three main allergic
diseases at a molecular level by identifying the proteins and cellular
processes that are common to them.
Methods
An in silico study based on computational analysis of the topology of
the protein interaction network was performed in order to characterize
the molecular mechanisms of multimorbidity of asthma, eczema and
rhinitis. As a first step, proteins associated to either disease were
identified using data mining approaches, and their overlap was
calculated. Secondly, a functional interaction network was built,
allowing to identify cellular pathways involved in allergic
multimorbidity. Finally, a network-based algorithm generated a ranked
list of newly predicted multimorbidity-associated proteins.
Results
Asthma, eczema and rhinitis shared a larger number of associated
proteins than expected by chance, and their associated proteins
exhibited a significant degree of interconnectedness in the interaction
network. There were 15 pathways involved in the multimorbidity of
asthma, eczema and rhinitis, including IL4 signaling and GATA3-related
pathways. A number of proteins potentially associated to these
multimorbidity processes were also obtained.
Conclusions
These results strongly support the existence of an allergic
multimorbidity cluster between asthma, eczema and rhinitis, and suggest
that type 2 signaling pathways represent a relevant multimorbidity
mechanism of allergic diseases. Furthermore, we identified new
candidates contributing to multimorbidity that may assist in identifying
new targets for multimorbid allergic diseases.
Συγγραφείς:
Aguilar, Daniel
Pinart, Mariona
Koppelman, Gerard H.
Saeys,
Yvan
Nawijn, Martijn C.
Postma, Dirkje S.
Akdis, Muebeccel
and Auffray, Charles
Ballereau, Stephane
Benet, Marta and
Garcia-Aymerich, Judith
Ramon Gonzalez, Juan
Guerra, Stefano and
Keil, Thomas
Kogevinas, Manolis
Lambrecht, Bart
Lemonnier,
Nathanael
Melen, Erik
Sunyer, Jordi
Valenta, Rudolf and
Valverde, Sergi
Wickman, Magnus
Bousquet, Jean
Oliva, Baldo
and Anto, Josep M.
