Heterogeneity of the cytokinome in undifferentiated arthritis progressing to rheumatoid arthritis and its change in the course of therapy. Move toward personalized medicine

Brzustewicz, Edyta; Bzoma, Izabella; Daca, Agnieszka; Szarecka, Maria; Bykowska, Malgorzata Sochocka; Witkowski, Jacek M.; Bryl, Ewa

doi:10.1016/j.cyto.2017.05.012

Cited by 7 publications

(4 citation statements)

References 31 publications

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“…The results of our study are in accordance with those of previous reports. 16 These conclusions suggest that dysregulation of the cytokine profile contributes to autoimmune processes, and undoubtedly plays crucial roles in the pathogenesis of SUA and its progression to RA. Moreover, the serum concentrations of IL-6 and TNF-α were significantly higher in RA patients than in SUA patients, further indicating the critical roles of these two proinflammatory cytokines in the development of RA.…”

Section: Discussionmentioning

confidence: 94%

“…15 As one form of UA characterized by autoantibody production, SUA will progress to RA as the most severe and persistent form. 16 RF and anti-CCP antibodies are the two most remarkable autoantibodies in RA and can be detected in serum several years before disease onset. 17 However, the presence of autoantibodies alone is not sufficient to predict progression to RA, with only 43% of anti-CCP-positive individuals fulfilling the 2010 ACR/EULAR criteria over 4 years.…”

Section: Discussionmentioning

confidence: 99%

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Decreased numbers and sex-based differences of circulating regulatory T cells in patients with seropositive undifferentiated arthritis

Niu

Yuan

Yan

et al. 2021

Therapeutic Advances in Chronic Disease

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Aims: CD4+ T cells play crucial roles as both mediators and regulators of the pathogenesis of rheumatoid arthritis (RA). However, the characteristics of CD4+ T cell subpopulations in the earliest stage of RA development remain unclear. Hence, we determined the proportions and absolute counts of circulating CD4+ T cell subsets in patients with seropositive undifferentiated arthritis (SUA), the early and preclinical stage of RA. Methods: Peripheral blood samples and clinical information were collected from 177 patients with SUA, 104 patients with RA, and 120 healthy controls. All patients were newly diagnosed and untreated. Proportions and absolute counts of CD4+ T cell subpopulations were determined by flow cytometric analysis. Results: In patients with SUA, percentages and absolute counts of circulating regulatory T (Treg) cells were decreased significantly and Th17/Treg cell ratios were abnormally increased, whereas Th17 cell numbers were similar to those in healthy controls. In addition, sex-based differences in circulating Treg cells were observed, with female SUA patients having lower proportions and absolute counts of Treg cells than those in males. Moreover, female patients with SUA had higher erythrocyte sedimentation rates and 28-joint Disease Activity Scores than those in males. Conclusion: Immune tolerance deficiency resulting from an abnormal reduction in circulating Treg cells might be the most crucial immunological event in the earliest stage of RA. The sex-specific disparity in Treg cells should also be considered for immunoregulatory and preventive strategies targeting early RA.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Decreased numbers and sex-based differences of circulating regulatory T cells in patients with seropositive undifferentiated arthritis

Niu

Yuan

Yan

et al. 2021

Therapeutic Advances in Chronic Disease

View full text Add to dashboard Cite

show abstract

“…For example, the comprehensive analysis of cytokine concentrations in sera and anti-CD3-stimulated PBMCs of patients who have undifferentiated arthritis progressing to RA revealed different cytokine profiles between patients refractory to the DMARD therapy and patients responding to the therapy, suggesting that cytokine patterns may be potentially used for the optimization of therapy introduction and monitoring. 100 Another study revealed that the determination of IL-1 and the IL-1Ra/IL-1 ratio in the supernatants of PBMCs cultured under resting conditions could be useful to predict the outcome of RA patients undergoing treatment with methotrexate and may characterize a subset of patients that is more responsive to IL-1-directed therapy. 101 Similarly, IL-1 measurement in whole blood cultured with lipopolysaccharides was found to predict the response to anti-TNF therapies in RA.…”

Section: Why When and How To Evaluate Cytokines?mentioning

confidence: 99%

The evaluation of cytokines to help establish diagnosis and guide treatment of autoinflammatory and autoimmune diseases

Nézondet

Poubelle

Pelletier

2020

Journal of Leukocyte Biology

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Our knowledge of the role of cytokines in pathologic conditions has increased considerably with the emergence of molecular and genetic studies, particularly in the case of autoinflammatory monogenic diseases. Many rare disorders, considered orphan until recently, are directly related to abnormal gene regulation, and the treatment with biologic agents (biologics) targeting cytokine receptors, intracellular signaling or specific cytokines improve the symptoms of an increasing number of chronic inflammatory diseases. As it is currently impossible to systematically conduct genetic studies for all patients with autoinflammatory and autoimmune diseases, the evaluation of cytokines can be seen as a simple, less time consuming, and less expensive alternative. This approach could be especially useful when the diagnosis of syndromes of diseases of unknown etiology remains problematic. The evaluation of cytokines could also help avoid the current trial-and-error approach, which has the disadvantages of exposing patients to ineffective drugs with possible unnecessary side effects and permanent organ damages. In this review, we discuss the various possibilities, as well as the limitations of evaluating the cytokine profiles of patients suffering from autoinflammatory and autoimmune diseases, with methods such as direct detection of cytokines in the plasma/serum or following ex vivo stimulation of PBMCs leading to the production of their cytokine secretome. The patients' secretome, combined with biomarkers ranging from genetic and epigenetic analyses to immunologic biomarkers, may help not only the diagnosis but also guide the choice of biologics for more efficient and rapid treatments.

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“…Fifteen years later, high-throughput technologies have evidenced the heterogeneity of patients suffering from complex diseases such as SLE or RA, which are now defined as pathotypes [ 65 ]. Because some cytokines are direct drivers of immunopathology and because the quantification of most cytokines is easily feasible with multiplex technology, we suggest that providing an extensive profiling of cytokines (in the blood or the affected tissue if accessible), a “cytokinome” as suggested by others [ 66 ], would be a useful tool to better define patients sub-groups by comparison with a reference of healthy subjects [ 67 ]. This approach, illustrated by the “multidimensional compass” illustrated in Figure 3 , would also be instrumental in defining the best therapeutic option for a patient, following its impact on the normalization of its cytokine profile and eventually adjusting it.…”

Section: Discussionmentioning

confidence: 99%

Crosstalk between Interleukin-1β and Type I Interferons Signaling in Autoinflammatory Diseases

Georgel

2021

Cells

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Interleukin-1β (IL-1β) and type I interferons (IFNs) are major cytokines involved in autoinflammatory/autoimmune diseases. Separately, the overproduction of each of these cytokines is well described and constitutes the hallmark of inflammasomopathies and interferonopathies, respectively. While their interaction and the crosstalk between their downstream signaling pathways has been mostly investigated in the frame of infectious diseases, little information on their interconnection is still available in the context of autoinflammation promoted by sterile triggers. In this review, we will examine the respective roles of IL-1β and type I IFNs in autoinflammatory/rheumatic diseases and analyze their potential connections in the pathophysiology of some of these diseases, which could reveal novel therapeutic opportunities.

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Heterogeneity of the cytokinome in undifferentiated arthritis progressing to rheumatoid arthritis and its change in the course of therapy. Move toward personalized medicine

Cited by 7 publications

References 31 publications

Decreased numbers and sex-based differences of circulating regulatory T cells in patients with seropositive undifferentiated arthritis

Decreased numbers and sex-based differences of circulating regulatory T cells in patients with seropositive undifferentiated arthritis

The evaluation of cytokines to help establish diagnosis and guide treatment of autoinflammatory and autoimmune diseases

Crosstalk between Interleukin-1β and Type I Interferons Signaling in Autoinflammatory Diseases

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