Circulating miRNA-19b as a biomarker of disease progression and treatment response to baricitinib in rheumatoid arthritis patients through miRNA profiling of monocytes

Marzena Ciechomska; Leszek Roszkowski; Tomasz Burakowski; Magdalena Massalska; Anna Felis-Giemza; Adria-Jaume Roura

doi:10.3389/fimmu.2023.980247

Circulating miRNA-19b as a biomarker of disease progression and treatment response to baricitinib in rheumatoid arthritis patients through miRNA profiling of monocytes

Front Immunol. 2023 Mar 28:14:980247. doi: 10.3389/fimmu.2023.980247. eCollection 2023.

Authors

Marzena Ciechomska¹, Leszek Roszkowski², Tomasz Burakowski¹, Magdalena Massalska¹, Anna Felis-Giemza³, Adria-Jaume Roura^{4

5}

Affiliations

¹ Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
² Department of Outpatient Clinics, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
³ Biologic Therapy Center, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
⁴ Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, Warsaw, Poland.
⁵ Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.

Abstract

Introduction: A number of studies have demonstrated a key role of miRNA isolated from cells, tissue or body fluids as disease-specific biomarkers of autoimmune rheumatic diseases including rheumatoid arthritis (RA) and systemic sclerosis (SSc). Also, the expression level of miRNA is changing during disease development, therefore miRNA can be used as biomarkers monitoring RA progression and treatment response. In this study we have investigated the monocytes-specific miRNA that could serve as potential biomarkers of disease progression observed in sera and synovial fluids (SF) in early (eRA) and advanced (aRA) RA and in RA patients before and 3 months after selective JAK inhibitor (JAKi) -baricitinib treatment.

Methods: Samples from healthy control (HC) (n=37), RA (n=44) and SSc (n=10) patients were used. MiRNA-seq of HC, RA, and SSc monocytes was performed to find versatile miRNA present in different rheumatic diseases. Selected miRNAs were validated in body fluids in eRA (<2 years disease onset) and aRA (>2 years disease onset) and RA patients receiving baricitinib.

Results: Using miRNA-seq, we selected top 6 miRNA out of 95 that were significantly changed in both RA and SSc monocytes compared to HC. To identify circulating miRNA predicting RA progression, these 6 miRNA were measured in eRA and aRA sera and SF. Interestingly, miRNA (-19b-3p, -374a-5p, -3614-5p) were significantly increased in eRA sera vs HC and even further upregulated in SF vs aRA sera. In contrast, miRNA-29c-5p was significantly reduced in eRA sera vs HC and even further decreased in SF vs aRA sera. Kegg pathway analysis predicted that miRNA were involved in inflammatory-mediated pathways. ROC analysis demonstrated that miRNA-19b-3p (AUC=0.85, p=0.04) can be used as biomarker predicting JAKi response.

Discussion: In conclusion, we identified and validated miRNA candidates which were present simultaneously in monocytes, sera, SF and that can be used as biomarkers predicting joint inflammation and monitoring therapy response to JAKi in RA patients.

Keywords: JAKi inhibitors; baricitinib; biomarkers; miRNA; monocytes; rheumatoid arthritis; sequencing; synovial fluids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Rheumatoid* / diagnosis
Arthritis, Rheumatoid* / drug therapy
Arthritis, Rheumatoid* / genetics
Biomarkers
Circulating MicroRNA*
Disease Progression
Humans
MicroRNAs* / metabolism
Monocytes / metabolism
Scleroderma, Systemic*

Substances

baricitinib
MicroRNAs
Biomarkers
Circulating MicroRNA

Grants and funding

This work was supported by grants 2015/16/S/NZ6/00041, 2018/30/E/NZ5/00104, both from the National Science Centre (Poland) (MC) and 2020/04/X/N25/01820 from National Science Centre (Poland) (MM).