Liquid biopsies to guide therapeutic decisions in rheumatoid arthritis

Coras, Roxana; Narasimhan, Rekha; Gumá, Mónica

doi:10.1016/j.trsl.2018.07.004

Cited by 12 publications

(12 citation statements)

References 114 publications

(128 reference statements)

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“…Importantly, differences were noted between the 2-step analyses (healthy controls versus individuals with CSA and individuals with CSA versus patients with RA) and the global analyses (healthy controls versus individuals with CSA versus patients with RA). Although the latter global approach mostly supported the role of AA and LOX as a whole, a compartmentalization was noted in the 2-step process, which aligns with the different oxylipin trajectories and allows for the identification of potential targets for tailored strategies, the main goal of personalized medicine (43), thus supporting the rationale of our analyses.…”

Section: Discussionsupporting

confidence: 69%

Profiling of Serum Oxylipins During the Earliest Stages of Rheumatoid Arthritis

Rodríguez‐Carrio

Coras

Alperi-López

et al. 2021

Arthritis & Rheumatology

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Objective. Eicosanoids modulate inflammation via complex networks involving different pathways and downstream mediators, including oxylipins. Although altered eicosanoids are linked to rheumatoid arthritis (RA), suggesting that metabolization is enhanced, the role of oxylipins in disease stratification remains unexplored. This study was undertaken to characterize oxylipin networks during the earliest stages of RA and evaluate their associations with clinical features and treatment outcomes. Methods. In total, 60 patients with early RA (according to the American College of Rheumatology/European League Against Rheumatism 2010 criteria), 11 individuals with clinically suspect arthralgia (CSA), and 28 healthy control subjects were recruited. Serum samples were collected at the time of onset. In the early RA group, 50 patients who had not been exposed to disease-modifying antirheumatic drug (DMARD) or glucocorticoid treatment at the time of recruitment were prospectively followed up at 6 and 12 months after having received conventional synthetic DMARDs. A total of 75 oxylipins, mostly derived from arachidonic, eicosapentanoic, and linoleic acids, were identified in the serum by liquid chromatography tandem mass spectrometry. Results. Univariate analyses demonstrated differences in expression patterns of 14 oxylipins across the RA, CSA, and healthy control groups, with each exhibiting a different trajectory. Network analyses revealed a strong grouping pattern of oxylipins in RA patients, whereas in individuals with CSA, a fuzzy network of oxylipins with higher degree and closeness was found. Partial least-squares discriminant analyses yielded variable important projection scores of >1 for 22 oxylipins, which allowed the identification of 2 clusters. Cluster usage differed among the groups (P = 0.003), and showed associations with disease severity and low rates of remission at 6 and 12 months in RA patients who were initially treatment-naive. Pathway enrichment analyses revealed different precursors and pathways between the groups, highlighting the relevance of the arachidonic acid pathway in individuals with CSA and the lipooxygenase pathway in patients with early RA. In applying distinct oxylipin signatures, subsets of seropositive and seronegative RA could be identified. Conclusion. Oxylipin networks differ across stages during the earliest phases of RA. These distinct oxylipin networks could potentially elucidate pathways with clinical relevance for disease progression, clinical heterogeneity, and treatment response.

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Section: Discussionsupporting

confidence: 69%

Profiling of Serum Oxylipins During the Earliest Stages of Rheumatoid Arthritis

Rodríguez‐Carrio

Coras

Alperi-López

et al. 2021

Arthritis & Rheumatology

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“…Although several biomarkers routinely used in RA management, such as anti-citrullinated protein autoantibodies (ACPA) and rheumatoid factor (RF) tests, have greatly contributed to improving the early diagnosis of RA [ 57 ], there is a high demand for novel biomarkers to further improve not only the diagnosis but also the stratification of patients and even the prediction of response to a specific therapy. CfDNA appears to be a good candidate as a biomarker of early diagnosis of RA but also for disease monitoring and prediction of response to treatment [ 58 ].…”

Section: Circulating Free Dna In Autoimmune Rheumatic Diseasesmentioning

confidence: 99%

Circulating Free DNA and Its Emerging Role in Autoimmune Diseases

Mondelo‐Macía

Castro‐Santos

Castillo‐García³

et al. 2021

JPM

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Liquid biopsies can be used to analyse tissue-derived information, including cell-free DNA (cfDNA), circulating rare cells, and circulating extracellular vesicles in the blood or other bodily fluids, representing a new way to guide therapeutic decisions in cancer. Among the new challenges of liquid biopsy, we found clinical application in nontumour pathologies, including autoimmune diseases. Since the discovery of the presence of high levels of cfDNA in patients with systemic lupus erythaematosus (SLE) in the 1960s, cfDNA research in autoimmune diseases has mainly focused on the overall quantification of cfDNA and its association with disease activity. However, with technological advancements and the increasing understanding of the role of DNA sensing receptors in inflammation and autoimmunity, interest in cfDNA and autoimmune diseases has not expanded until recently. In this review, we provide an overview of the basic biology of cfDNA in the context of autoimmune diseases as a biomarker of disease activity, progression, and prediction of the treatment response. We discuss and integrate available information about these important aspects.

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“…Different options have been proposed, essentially related to a pathobiology‐driven strategy, based upon either a synovial biopsy, 111 or a liquid biopsy strategy, relying on the identification of circulating biomarkers. Specifically, in terms of EVs, there is evidence that some miRNAs might be useful for this purpose 112 . Evidence suggests that EV‐derived miRNAs could be used as potential prediction of response to therapy in RA patients.…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

“…Specifically, in terms of EVs, there is evidence that some miRNAs might be useful for this purpose. 112 Evidence suggests that EV-derived miRNAs could be used as potential prediction of response to therapy in RA patients. Methotrexate treatment (DMARDs) can increase the whole blood expression of some miRNA 113 : hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p have all been proposed as potential predictors of response, 114 including in patients treated with anti-TNF/cDMARD.…”

Section: Evs and Ra Biomarkersmentioning

confidence: 99%

Chicken-or-egg question: Which came first, extracellular vesicles or autoimmune diseases?

Maione

Cappellano

Bellan

et al. 2020

Journal of Leukocyte Biology

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Extracellular vesicles (EVs) have attracted great interest as contributors to autoimmune disease (AD) pathogenesis, owing to their immunomodulatory potential; they may also play a role in triggering tolerance disruption, by delivering auto-antigens. EVs are released by almost all cell types, and afford paracrine or distal cell communication, functioning as biological carriers of active molecules including lipids, proteins, and nucleic acids. Depending on stimuli from the external microenvironment or on their cargo, EVs can promote or suppress immune responses. ADs are triggered by inappropriate immune-system activation against the self, but their precise etiology is still poorly understood. Accumulating evidence indicates that lifestyle and diet have a strong impact on their clinical onset and development. However, to date the mechanisms underlying AD pathogenesis are not fully clarified, and reliable markers, which would provide early prediction and disease progression monitoring, are lacking. In this connection, EVs have recently been indicated as a promising source of AD biomarkers. Although EV isolation is currently based on differential centrifugation or density-gradient ultracentrifugation, the resulting co-isolation of contaminants (i.e., protein aggregates), and the pooling of all EVs in one sample, limit this approach to abundantly-expressed EVs. Flow cytometry is one of the most promising methods for detecting EVs as biomarkers, and may have diagnostic applications. Furthermore, very recent findings describe a new method for identifying and sorting EVs by flow cytometry from freshly collected body fluids, based on specific EV surface markers.

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Liquid biopsies to guide therapeutic decisions in rheumatoid arthritis

Cited by 12 publications

References 114 publications

Profiling of Serum Oxylipins During the Earliest Stages of Rheumatoid Arthritis

Profiling of Serum Oxylipins During the Earliest Stages of Rheumatoid Arthritis

Circulating Free DNA and Its Emerging Role in Autoimmune Diseases

Chicken-or-egg question: Which came first, extracellular vesicles or autoimmune diseases?

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