Circulating MiRNA-19b As a Biomarker of Disease Progression and Treatment Response to Baricitinib in Rheumatoid Arthritis Patients Through MiRNA Profiling of Monocytes

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Apr 14

PMID 37056771

Authors

Marzena Ciechomska

Leszek Roszkowski

Tomasz Burakowski

Magdalena Massalska

Anna Felis-Giemza

Adria-Jaume Roura

Affiliations

Soon will be listed here.

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.

Citing Articles

Cell-Based Therapy and Genome Editing as Emerging Therapeutic Approaches to Treat Rheumatoid Arthritis.

Chasov V, Ganeeva I, Zmievskaya E, Davletshin D, Gilyazova E, Valiullina A Cells. 2024; 13(15.

PMID: 39120313 PMC: 11312096. DOI: 10.3390/cells13151282.

Role of microRNAs in Immune Regulation with Translational and Clinical Applications.

Gaal Z Int J Mol Sci. 2024; 25(3).

PMID: 38339220 PMC: 10856342. DOI: 10.3390/ijms25031942.

DNA Methylation Signatures of Response to Conventional Synthetic and Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) in Rheumatoid Arthritis.

Wang S, Lewis M, Pitzalis C Biomedicines. 2023; 11(7).

PMID: 37509625 PMC: 10377185. DOI: 10.3390/biomedicines11071987.

References

Zhou Y, Deng L, Zhao D, Chen L, Yao Z, Guo X . MicroRNA-503 promotes angiotensin II-induced cardiac fibrosis by targeting Apelin-13. J Cell Mol Med. 2016; 20(3):495-505. PMC: 4759464. DOI: 10.1111/jcmm.12754. View

Ludwig N, Leidinger P, Becker K, Backes C, Fehlmann T, Pallasch C . Distribution of miRNA expression across human tissues. Nucleic Acids Res. 2016; 44(8):3865-77. PMC: 4856985. DOI: 10.1093/nar/gkw116. View

Stypinska B, Wajda A, Walczuk E, Olesinska M, Lewandowska A, Walczyk M . The Serum Cell-Free microRNA Expression Profile in MCTD, SLE, SSc, and RA Patients. J Clin Med. 2020; 9(1). PMC: 7020053. DOI: 10.3390/jcm9010161. View

Almenar-Perez E, Sarria L, Nathanson L, Oltra E . Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Sci Rep. 2020; 10(1):2064. PMC: 7005890. DOI: 10.1038/s41598-020-58506-5. View

Miao C, Wang X, Zhou W, Huang J . The emerging roles of exosomes in autoimmune diseases, with special emphasis on microRNAs in exosomes. Pharmacol Res. 2021; 169:105680. DOI: 10.1016/j.phrs.2021.105680. View

van den Hoogen F, Khanna D, Fransen J, Johnson S, Baron M, Tyndall A . 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2013; 72(11):1747-55. DOI: 10.1136/annrheumdis-2013-204424. View

Roszkowski L, Ciechomska M . Tuning Monocytes and Macrophages for Personalized Therapy and Diagnostic Challenge in Rheumatoid Arthritis. Cells. 2021; 10(8). PMC: 8392289. DOI: 10.3390/cells10081860. View

Cron M, Payet C, Fayet O, Maillard S, Truffault F, Fadel E . Decreased expression of miR-29 family associated with autoimmune myasthenia gravis. J Neuroinflammation. 2020; 17(1):294. PMC: 7545844. DOI: 10.1186/s12974-020-01958-3. View

Chen C, Chen H . Clinical Diagnosis Value of miR-29b-3p in Peripheral Blood Mononuclear Cells and Synovial Fluid Among Osteoarthritis Patients. Clin Lab. 2019; 65(8). DOI: 10.7754/Clin.Lab.2019.190139. View

10.

Moutsopoulos H . Autoimmune rheumatic diseases: One or many diseases?. J Transl Autoimmun. 2022; 4:100129. PMC: 8716565. DOI: 10.1016/j.jtauto.2021.100129. View

11.

Cutolo M, Soldano S, Smith V . Pathophysiology of systemic sclerosis: current understanding and new insights. Expert Rev Clin Immunol. 2019; 15(7):753-764. DOI: 10.1080/1744666X.2019.1614915. View

12.

van den Hoogen F, Boerbooms A, Swaak A, Rasker J, van Lier H, van de Putte L . Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial. Br J Rheumatol. 1996; 35(4):364-72. DOI: 10.1093/rheumatology/35.4.364. View

13.

Kong R, Gao J, Si Y, Zhao D . Combination of circulating miR-19b-3p, miR-122-5p and miR-486-5p expressions correlates with risk and disease severity of knee osteoarthritis. Am J Transl Res. 2017; 9(6):2852-2864. PMC: 5489886. View

14.

Ciechomska M, Wojtas B, Swacha M, Olesinska M, Benes V, Maslinski W . Global miRNA and mRNA expression profiles identify miRNA-26a-2-3p-dependent repression of IFN signature in systemic sclerosis human monocytes. Eur J Immunol. 2020; 50(7):1057-1066. DOI: 10.1002/eji.201948428. View

15.

Xie Y, Chen W, Zhao M, Xu Y, Yu H, Qin J . Exploration of Exosomal miRNAs from Serum and Synovial Fluid in Arthritis Patients. Diagnostics (Basel). 2022; 12(2). PMC: 8871287. DOI: 10.3390/diagnostics12020239. View

16.

Zedan A, Hansen T, Assenholt J, Pleckaitis M, Madsen J, Osther P . microRNA expression in tumour tissue and plasma in patients with newly diagnosed metastatic prostate cancer. Tumour Biol. 2018; 40(5):1010428318775864. DOI: 10.1177/1010428318775864. View

17.

Zhou B, Zuo X, Li Y, Gao S, Dai X, Zhu H . Integration of microRNA and mRNA expression profiles in the skin of systemic sclerosis patients. Sci Rep. 2017; 7:42899. PMC: 5314349. DOI: 10.1038/srep42899. View

18.

Cojocaru M, Cojocaru I, Silosi I, Vrabie C . Pulmonary manifestations of systemic autoimmune diseases. Maedica (Bucur). 2012; 6(3):224-9. PMC: 3282547. View

19.

Philippe L, Alsaleh G, Suffert G, Meyer A, Georgel P, Sibilia J . TLR2 expression is regulated by microRNA miR-19 in rheumatoid fibroblast-like synoviocytes. J Immunol. 2011; 188(1):454-61. DOI: 10.4049/jimmunol.1102348. View

20.

Walker K, Pope J . Treatment of systemic sclerosis complications: what to use when first-line treatment fails--a consensus of systemic sclerosis experts. Semin Arthritis Rheum. 2012; 42(1):42-55. DOI: 10.1016/j.semarthrit.2012.01.003. View