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. 2023 Jan;78(1):141-155.
doi: 10.1111/all.15480. Epub 2022 Aug 29.

Serum exosome inflamma-miRs are surrogate biomarkers for asthma phenotype and severity

Sara Vázquez-Mera  1   2 , Laura Martelo-Vidal  1   2 , Pablo Miguéns-Suárez  1   2 , Paula Saavedra-Nieves  3 , Pilar Arias  1   2 , Coral González-Fernández  4 , Mar Mosteiro-Añón  5 , María Dolores Corbacho-Abelaira  6 , Marina Blanco-Aparicio  7 , Paula Méndez-Brea  8 , Francisco Javier Salgado  1   2 , Juan José Nieto-Fontarigo  2 , Francisco Javier González-Barcala  2   9   10   11
Affiliations

Serum exosome inflamma-miRs are surrogate biomarkers for asthma phenotype and severity

Sara Vázquez-Mera et al. Allergy. 2023 Jan.

Abstract

Background: Asthma is a heterogeneous disease with several phenotypes, endotypes and severity degrees, in which different T-cell subpopulations are involved. These cells express specific miRNAs (i.e. inflamma-miRs) that can be released to serum in exosomes after activation and be used as biomarkers of underlying inflammation. Thus, we aim to evaluate specific T-cell miRNA signatures in serum exosomes from different subgroups of asthmatic patients.

Methods: Samples from healthy donors (N = 30) and patients (N = 119) with different asthma endotypes (T2high -Atopic/T2high -Non-atopic/T2low ) and severity degrees (mild/MA and moderate-severe/MSA) were used. Demographic, clinical, haematological and biochemical characteristics were collected. Twelve miRNAs previously associated with different Th subsets were preselected and their levels in serum exosome samples were measured using RTqPCR.

Results: We detected five miRNAs with high confidence in serum exosomes: miR-16-5p, miR-21-5p, miR-126-3p, miR146a-5p and miR-215-5p. All of them, except miR-16-5p were upregulated in MSA patients compared to MA. A logistic regression model including each of these miRNAs was created to discriminate both conditions, rendering a ROC curve AUC of 0.896 (0.830-0.961). miR-21-5p and miR-126-3p, both involved in Th1/Th2 differentiation, were specifically augmented in T2high -Atopic patients. Of note, all these changes were found in samples collected in autumn. On the contrary, IL-6high patients with MSA, which were more obese, older, with higher neutrophil and basophil counts and TNF levels, displayed a decrease of miR-21-5p, miR-126-3p and miR-146a-5p.

Conclusion: Immune-related miRNAs, including miR-21-5p, miR-126-3p, miR-146a-5p and miR-215-5p, can be used as clinically relevant non-invasive biomarkers of the phenotype/endotype and severity of asthma.

Keywords: asthma; biomarker; endotypes; miRNAs; phenotypes.

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References

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