INVESTIGATION ON POSSIBLE IMMUNOLOGICAL AND MOLECULAR MARKERS OF DIFFERENT PHENOTYPES OF ASTHMA: A CASE-CONTROL STUDY
Severe asthma. Biomarkers. Pro-inflammatory cytokines. Omics. Hippo pathway. microRNAs.
Asthma is a chronic inflammatory, complex and multifactorial disease with several phenotypes. Among the severe asthma phenotypes, there is the subtype 'asthma resistant to treatment, where asthma control is not achieved, even using the maximum maintenance treatment. The aim of this study was to investigate immunological and molecular biomarkers of severe asthma phenotypes in a case-control study, in individuals from the ProAr cohort, in Salvador, Bahia, Brazil. 67 subjects were assessed, divided into three asthma subgroups [17 with severe treatment-resistant asthma (SAR), 22 with treatment-controlled severe asthma (SAC) 19 with mild to moderate asthma (MMA)] and a no asthma (NA) control group including 9 subjects. For immunological analysis, cytokines were measured using a multiplex kit using Luminex technology (Merck, Germany) and the differential sputum cell count was performed by cytospin preparations. The total RNA transcriptome (SAR = 2; MMA = 2) was performed on the Ion Torrent S5 platform, using an Ion 540 chip (Thermo Fisher Scientific, CA, USA). The proteome (three samples for the SAR and MMA groups) was carried out by trypsinization and the peptides were analyzed by mass spectrometry coupled to liquid chromatography (LC-MS / MS). The results suggest the presence of a treatment-resistant asthma phenotype characterized by the production of proinflammatory cytokines (IL-6 and TNF), mixed cell profile, independent of the Th2 response. Omic studies have shown positive regulation of inflammatory pathways (TLRs and the JAK-STAT pathways) and under representation of the Hippo pathway and microRNA profile that modulate important inflammatory mechanisms associated with negative regulation of the Hippo pathway.