Exploring the Extracellular Vesicle MicroRNA Expression Repertoire in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis Treated with TNF Inhibitors

Wielińska, Joanna; Crossland, Rachel E; Łacina, Piotr; Świerkot, Jerzy; Bugaj, Bartosz; Dickinson, Anne; Bogunia‐Kubik, Katarzyna

doi:10.1155/2021/2924935

Cited by 7 publications

(5 citation statements)

References 128 publications

(122 reference statements)

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“…The miRNA content of exosomes has been found to differ from their parent cells, indicating that their cargo packaging is a selective process 19 20. Profiling plasma exosomal miRNAs hse already contributed to increased knowledge of the role of exosomes in the pathogenesis of AS 21–28…”

Section: Introductionmentioning

confidence: 99%

Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis

et al. 2023

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IntroductionRecent advances in understanding the biology of ankylosing spondylitis (AS) using innovative genomic and proteomic approaches offer the opportunity to address current challenges in AS diagnosis and management. Altered expression of genes, microRNAs (miRNAs) or proteins may contribute to immune dysregulation and may play a significant role in the onset and persistence of inflammation in AS. The ability of exosomes to transport miRNAs across cells and alter the phenotype of recipient cells has implicated exosomes in perpetuating inflammation in AS. This study reports the first proteomic and miRNA profiling of plasma-derived exosomes in AS using comprehensive computational biology analysis.MethodsPlasma samples from patients with AS and healthy controls (HC) were isolated via ultracentrifugation and subjected to extracellular vesicle flow cytometry analysis to characterise exosome surface markers by a multiplex immunocapture assay. Cytokine profiling of plasma-derived exosomes and cell culture supernatants was performed. Next-generation sequencing was used to identify miRNA populations in exosomes enriched from plasma fractions. CD4+ T cells were sorted, and the frequency and proliferation of CD4+ T-cell subsets were analysed after treatment with AS-exosomes using flow cytometry.ResultsThe expression of exosome marker proteins CD63 and CD81 was elevated in the patients with AS compared with HC (q<0.05). Cytokine profiling in plasma-derived AS-exosomes demonstrated downregulation of interleukin (IL)-8 and IL-10 (q<0.05). AS-exosomes cocultured with HC CD4+ T cells induced significant upregulation of IFNα2 and IL-33 (q<0.05). Exosomes from patients with AS inhibited the proliferation of regulatory T cells (Treg), suggesting a mechanism for chronically activated T cells in this disease. Culture of CD4+ T cells from healthy individuals in the presence of AS-exosomes reduced the proliferation of FOXP3+ Treg cells and decreased the frequency of FOXP3+IRF4+ Treg cells. miRNA sequencing identified 24 differentially expressed miRNAs found in circulating exosomes of patients with AS compared with HC; 22 of which were upregulated and 2 were downregulated.ConclusionsIndividuals with AS have different immunological and genetic profiles, as determined by evaluating the exosomes of these patients. The inhibitory effect of exosomes on Treg in AS suggests a mechanism contributing to chronically activated T cells in this disease.

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Section: Introductionmentioning

confidence: 99%

Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis

et al. 2023

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“…They also identified miRNAs which have not been described earlier in terms of RA and specific ones to distinguish between RA and ankylosing spondylitis (AS). 37 …”

Section: Extracellular Vesicles and Exosomes In The Pathophysiology O...mentioning

confidence: 99%

Updates on the Pathophysiology and Therapeutic Potential of Extracellular Vesicles with Focus on Exosomes in Rheumatoid Arthritis

Gavriilidi,

Wielińska,

Bogunia-Kubik

2024

JIR

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Rheumatoid arthritis (RA) is an incurable autoimmune disease with high morbidity and socioeconomic burden. Advances in therapeutics have improved patients’ quality of life, however due to the complex disease pathophysiology and heterogeneity, 30% of patients do not respond to treatment. Understanding how different genetic and environmental factors contribute to disease initiation and development as well as uncovering the interactions of immune components is key to the implementation of effective and safe therapies. Recently, the role of extracellular vesicles (EVs) in RA development and possible treatment has been an area of interest. EVs are small lipid-bound entities, often containing genetic material, proteins, lipids and amino acids, facilitating paracrine intercellular communication. They are secreted by all cells, and it is believed that they possess regulatory functions due to high complexity and functional diversity. Although it has been shown that EVs participate in RA pathophysiology, through immune modulation, their exact role remains elusive. Furthermore, EVs could be a promising therapeutic agent in various diseases including RA, due to their biocompatibility, low toxicity and possible manipulation, but further research is required in this area. This review provides a comprehensive discussion of disease pathophysiology and summarizes the latest knowledge regarding the role and therapeutic potential of EVs in RA.

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“…Studies on ROC curve analysis and logistic regression models have suggested that the combination of circ_0002715 and circ_0035197 might be a biomarker for diagnosis and disease activity in new-onset RA (AUC = 0.758, sensitivity = 72.9%, and specificity = 71.4%). They can differentiate RA patients from patients with SLE or AS and HCs (188). circ_AFF2 levels were found in one study to be upregulated in the peripheral blood of RA patients, increasing TAB2 expression to promote RA progression by sponging miR-375, which can be used as a biomarker for RA diagnosis and treatment (189).…”

Section: Candidate Rnas As Biomarkers For Ramentioning

confidence: 99%

Section: Candidate Rnas As Biomarkers For Ramentioning

confidence: 99%

Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of rheumatoid arthritis

Jiang

Zhong

et al. 2023

Front. Immunol.

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In recent years, diagnostic and therapeutic approaches for rheumatoid arthritis (RA) have continued to improve. However, in the advanced stages of the disease, patients are unable to achieve long-term clinical remission and often suffer from systemic multi-organ damage and severe complications. Patients with RA usually have no overt clinical manifestations in the early stages, and by the time a definitive diagnosis is made, the disease is already at an advanced stage. RA is diagnosed clinically and with laboratory tests, including the blood markers C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and the autoantibodies rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA). However, the presence of RF and ACPA autoantibodies is associated with aggravated disease, joint damage, and increased mortality, and these autoantibodies have low specificity and sensitivity. The etiology of RA is unknown, with the pathogenesis involving multiple factors and clinical heterogeneity. The early diagnosis, subtype classification, and prognosis of RA remain challenging, and studies to develop minimally invasive or non-invasive biomarkers in the form of biofluid biopsies are becoming more common. Non-coding RNA (ncRNA) molecules are composed of long non-coding RNAs, small nucleolar RNAs, microRNAs, and circular RNAs, which play an essential role in disease onset and progression and can be used in the early diagnosis and prognosis of RA. In this review of the diagnostic and prognostic approaches to RA disease, we provide an overview of the current knowledge on the subject, focusing on recent advances in mRNA–ncRNA as diagnostic and prognostic biomarkers from the biofluid to the tissue level.

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Exploring the Extracellular Vesicle MicroRNA Expression Repertoire in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis Treated with TNF Inhibitors

Cited by 7 publications

References 128 publications

Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis

Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis

Updates on the Pathophysiology and Therapeutic Potential of Extracellular Vesicles with Focus on Exosomes in Rheumatoid Arthritis

Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of rheumatoid arthritis

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