Circulating extracellular vesicles and small non-coding RNAs cargo in idiopathic inflammatory myopathies reveal differences across myositis subsets

Chiara Franco; Alessandra Giannella; Michela Gasparotto; Elisabetta Zanatta; Anna Ghirardello; Federico Pettorossi; Zahrà Rahmè; Roberto Depascale; Davide Ragno; Gioele Bevilacqua; Elisa Bellis; Luca Iaccarino; Andrea Doria; Giulio Ceolotto; Mariele Gatto

doi:10.1016/j.jaut.2024.103255

Circulating extracellular vesicles and small non-coding RNAs cargo in idiopathic inflammatory myopathies reveal differences across myositis subsets

J Autoimmun. 2024 Jul:147:103255. doi: 10.1016/j.jaut.2024.103255. Epub 2024 May 25.

Authors

Affiliations

¹ Unit of Rheumatology, Department of Medicine, University of Padua, Padua, Italy. Electronic address: chiara.franco@aopd.veneto.it.
² Division of Thrombotic and Hemorrhagic Diseases, Department of Medicine, University of Padua, Padua, Italy. Electronic address: alessandra.giannella@unipd.it.
³ Unit of Rheumatology, Department of Medicine, University of Padua, Padua, Italy. Electronic address: gasparotto.michela@gmail.com.
⁴ Unit of Rheumatology, Department of Medicine, University of Padua, Padua, Italy. Electronic address: elisabetta.zanatta@unipd.it.
⁵ Unit of Rheumatology, Department of Medicine, University of Padua, Padua, Italy. Electronic address: anna.ghirardello@unipd.it.
⁶ Unit of Rheumatology, Department of Medicine, University of Padua, Padua, Italy. Electronic address: fedepetto@gmail.com.
⁷ Unit of Rheumatology, Department of Medicine, University of Padua, Padua, Italy. Electronic address: zahra.rahme@studenti.unipd.it.
⁸ Unit of Rheumatology, Department of Medicine, University of Padua, Padua, Italy. Electronic address: rob.depascale93@gmail.com.
⁹ Unit of Rheumatology, Department of Medicine, University of Padua, Padua, Italy. Electronic address: davide.ragno@studenti.unipd.it.
¹⁰ Unit of Emergency Medicine, Department of Medicine, University of Padua, Padua, Italy. Electronic address: gioele.bevilacqua@studenti.unipd.it.
¹¹ Academic Rheumatology Centre, Department of Clinical and Biological Sciences, University of Turin, AO Mauriziano, Turin, Italy. Electronic address: elisa.bellis@unito.it.
¹² Unit of Rheumatology, Department of Medicine, University of Padua, Padua, Italy. Electronic address: luca.iaccarino@unipd.it.
¹³ Unit of Rheumatology, Department of Medicine, University of Padua, Padua, Italy. Electronic address: adoria@unipd.it.
¹⁴ Unit of Emergency Medicine, Department of Medicine, University of Padua, Padua, Italy. Electronic address: giulio.ceolotto@unipd.it.
¹⁵ Unit of Rheumatology, Department of Medicine, University of Padua, Padua, Italy; Academic Rheumatology Centre, Department of Clinical and Biological Sciences, University of Turin, AO Mauriziano, Turin, Italy. Electronic address: mariele.gatto@unito.it.

PMID: 38788539
DOI: 10.1016/j.jaut.2024.103255

Abstract

Objective: To investigate the epigenetic footprint of idiopathic inflammatory myopathies (IIM) through characterization of circulating extracellular vesicles (EVs) and the expression of EV-derived small non-coding RNAs (sncRNAs).

Methods: In this cross-sectional study, EVs were isolated by size-exclusion chromatography from plasma of patients with IIM and age- and sex-matched healthy donors (HD). EV-derived sncRNAs were sequenced and quantified using Next-Generation Sequencing (NGS). Following quality control and normalization, filtered count reads were used for differential microRNA (miRNA) and piwi-interacting RNA (piRNA) expression analyses. Putative gene targets enriched for pathways implicated in IIM were analyzed. Patients' clinical and laboratory characteristics at the time of sampling were recorded.

Results: Forty-seven IIM patients and 45 HD were enrolled. MiR-486-5p (p < 0.01), miR-122-5p, miR-192-5p, and miR-32-5p were significantly upregulated (p < 0.05 for all), while miR-142-3p (p < 0.001), miR-141-3p (p < 0.01), let-7a-5p (p < 0.05) and miR-3613-5p (p < 0.05) downregulated in EVs from IIM patients versus HD. MiR-486-5p was associated with raised muscle enzymes levels. Several target genes of up/downregulated miRNAs in IIM participate in inflammation, necroptosis, interferon and immune signaling. Six piRNAs were significantly dysregulated in IIM EVs versus HD (p < 0.05). Within IIM, miR-335-5p was selectively upregulated and miR-27a-5p downregulated in dermatomyositis (n = 21, p < 0.01). Finally, plasma EV levels were significantly increased in cancer-associated myositis (CAM, n = 12) versus non-CAM IIM (n = 35, p = 0.02) and HD (p < 0.01). EVs cargo in CAM was significantly enriched of let-7f-5p and depleted of miR-143-3p.

Conclusion: Through an unbiased screening of EV-derived sncRNAs, we characterize miRNAs and piRNAs in the EVs cargo as potential biomarkers and modifiers of diverse IIM phenotypes.

Keywords: Biomarkers; Extracellular vesicles; Idiopathic inflammatory myopathies; microRNAs.

MeSH terms

Adult
Aged
Biomarkers*
Cross-Sectional Studies
Extracellular Vesicles* / genetics
Extracellular Vesicles* / metabolism
Female
Gene Expression Profiling
High-Throughput Nucleotide Sequencing
Humans
Male
MicroRNAs* / genetics
Middle Aged
Myositis* / blood
Myositis* / diagnosis
Myositis* / genetics
Myositis* / immunology
RNA, Small Untranslated* / blood
RNA, Small Untranslated* / genetics

Substances

MicroRNAs
RNA, Small Untranslated
Biomarkers