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

Frontiers in Immunology

Immunology

Anna Felis-Giemza¹  Leszek Roszkowski²  Magdalena Massalska³  Tomasz Burakowski³  Marzena Ciechomska³  Adria-Jaume Roura⁴ 

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

关键词: rheumatoid arthritis;    miRNA;    baricitinib;    monocytes;    sequencing;    synovial fluids;    biomarkers;    JAKi inhibitors;   

DOI  :  10.3389/fimmu.2023.980247

 received in 2022-06-28, accepted in 2023-03-14,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionA 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.MethodsSamples 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.ResultsUsing 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.DiscussionIn 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.

【 授权许可】

Unknown   
Copyright © 2023 Ciechomska, Roszkowski, Burakowski, Massalska, Felis-Giemza and Roura