5' tiRNA Gly-GCC as a potential new biomarker for asthma phenotyping

GROSSO, J; CLAUS, C; MARAVAL, M. B; ARDUSSO, M; ARDUSSO, L; SPINELLI, S.V.

virtual

Congreso; Reunión SAI 2021; 2021

The heterogeneous nature of asthma has been understood for decades, but this feature of the disease is becoming increasingly important in the era of specific biologic therapy. Unfortunately, accurate biomarkers for asthma phenotyping remain an unmet medical need. tRNA-derived fragments have been proposed as markers of different diseases and among them, tiRNA are of particular interest since they are produced under stress conditions. To test whether tiARNs can be used to evaluate asthma severity, 5' tiRNA Glu-CTC and 5' tiRNA Gly-GCC, two abundant tiRNAs in saliva, were quantified in sputum samples of patients (n=42, 13 healthy controls and 29 asthmatics, 13 of which are severe cases). Their levels were assessed both in cells obtained from the sample (mainly leukocytes) and in sputum supernatants. We found that 5' tiRNA Gly-GCC levels were significantly elevated only in supernatants from patients with severe asthma. This lack of correlation with what is observed in sputum cells suggests that tiRNAs could be secreted by the bronchial epithelium. Similar results were obtained when we discriminated patients according to sputum inflammatory phenotype, where extracellular 5' tiRNAGly-GCC showed increased levels in eosinophilic infiltrates, a hallmark of severe patients. Interestingly, levels of this tiRNA were significantly correlated with the expression of angiogenin (ANG) in circulating leukocytes. ANG is the enzyme responsible for tiRNA production through specific cleavage of tRNAs in their anticodon loop. High expression of ANG in blood samples from severe and eosinophilic patients indicates that this pathway is activated in asthma. In line with these findings, levels of 5' tiRNA Gly-GCC and ANG are positively correlated with production of pro-inflammatory cytokines such as IL-1, IL-6 and IL-8 in sputum. In sum, our results contribute to shed light on the role of tiARNs in the pathogenesis of asthma and suggest the potential use of 5'tiRNA-Gly-GCC for its phenotyping.