Canonical pathways altered by the EVs signature
The coordinated function displayed by the proteins contained in the
anaphylactic panel would support information about the molecular bases
of the reaction, especially of those exclusively found in the acute
condition. Therefore, it was performed two comprehensive analyses: a
“manual” based in the Uniprot database and an in silicoapproach through IPA. The first revealed a major group of immune
proteins and those participating of the cellular structure, supporting a
role of EVs in anaphylaxis. A summary of the major cell location as well
as the main biological processes of identified EV markers is illustrated
in Figures 4A-B . In agreement, the in silico IPA
revealed different canonical pathways, candidates to underlie signaling
in anaphylaxis. A list including those with higher significance is
showed in Figure 4C . This analysis showed that these proteins
altered involve mainly immunological processes such as degranulation of
cells (mainly neutrophils) and adhesion-binding of leukocytes
(Sup Table 2 ). A major interest was aroused by the
appearance/repetition of same molecules participating in the different
top canonical pathways; like CDC42. Therefore, to better visualize
associations between the key proteins and their multiple participation
in the functional networks described previously, a graphical
representation based on STRING analysis was performed. As expected, this
demonstrated that some AnEVs proteins are grouped in a unique cluster,
such is the case of the keratinocytes include in the glucocorticoid
receptor signaling pathway. In addition, Clathrin-mediated endocytosis,
a process related with the own biology of
EVs, was also observed.