Novel insights into the role of inflammasomes in autoimmune and metabolic rheumatic diseases

Deuteraiou, Kleopatra; Kitas, George D.; Garyfallos, Alexandros; Dimitroulas, Theodoros

doi:10.1007/s00296-018-4074-5

Cited by 22 publications

(10 citation statements)

References 70 publications

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“…22 Since then, studies at the functional and genetic levels have In the last two decades, the knowledge about the inflammasomes has dramatically evolved. This has led to the differentiation of several previous orphan diseases being regrouped into new syndromes defined by their genetic associations (see recent reviews [24][25][26][27] ). These new syndromes share an overproduction of proinflammatory members of the IL-1 family, in particular IL-1 and IL-18, which could be present in the blood or the conditioned media from PBMCs of patients.…”

Section: Cytokines Implicated In Autoinflammationmentioning

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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Section: Cytokines Implicated In Autoinflammationmentioning

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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“…Both hydroxychloroquine and VX740 are the potential candidates for the treatment of RA in the near future through modulation of inflammasomes [158]. Hydroxychloroquine (complex formationof the inflammasome) represses overexpression of TLR leading to inhibit the secretion of TNF-α.…”

Section: Clinical Trials and The Spotlight For Ra In The Futurementioning

confidence: 99%

Immunopathogenic Mechanisms and Novel Immune-Modulated Therapies in Rheumatoid Arthritis

Chen

Lin

Chen

et al. 2019

IJMS

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Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease of unknown etiology. It is characterized by the presence of rheumatoid factor and anticitrullinated peptide antibodies. The orchestra of the inflammatory process among various immune cells, cytokines, chemokines, proteases, matrix metalloproteinases (MMPs), and reactive oxidative stress play critical immunopathologic roles in the inflammatory cascade of the joint environment, leading to clinical impairment and RA. With the growing understanding of the immunopathogenic mechanisms, increasingly novel marked and potential biologic agents have merged for the treatment of RA in recent years. In this review, we focus on the current understanding of pathogenic mechanisms, highlight novel biologic disease-modifying antirheumatic drugs (DMRADs), targeted synthetic DMRADs, and immune-modulating agents, and identify the applicable immune-mediated therapeutic strategies of the near future. In conclusion, new therapeutic approaches are emerging through a better understanding of the immunopathophysiology of RA, which is improving disease outcomes better than ever.

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“…The second signal, triggered by MSU crystals, leads to activation of multiprotein intracellular NLRP3 inflammasomes, which contain pro-caspase 1 [4]. Next, active caspase 1 cleaves precursors of interleukins 1 beta and 18 (pro-IL-1β and pro-IL-18) to generate the active forms (IL-1β and IL-18) [5,6]. Secretion of IL-1β leads to recruitment of neutrophils to the site of inflammation, production of additional pro-inflammatory cytokines, and bone/cartilage degradation [3,7].…”

Section: Introductionmentioning

confidence: 99%

Interaction of the p.Q141K Variant of the ABCG2 Gene with Clinical Data and Cytokine Levels in Primary Hyperuricemia and Gout

Horváthová

Bohatá

Pavlı́ková

et al. 2019

JCM

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Gout is an inflammatory arthritis influenced by environmental risk factors and genetic variants. The common dysfunctional p.Q141K allele of the ABCG2 gene affects gout development. We sought after the possible association between the p.Q141K variant and gout risk factors, biochemical, and clinical determinants in hyperuricemic, gouty, and acute gouty arthritis cohorts. Further, we studied the correlation of p.Q141K allele and levels of pro-/anti-inflammatory cytokines. Coding regions of the ABCG2 gene were analyzed in 70 primary hyperuricemic, 182 gout patients, and 132 normouricemic individuals. Their genotypes were compared with demographic and clinical parameters. Plasma levels of 27 cytokines were determined using a human multiplex cytokine assay. The p.Q141K variant was observed in younger hyperuricemic/gout individuals (p = 0.0003), which was associated with earlier disease onset (p = 0.004), trend toward lower BMI (p = 0.056), and C-reactive protein (CRP, p = 0.007) but a higher glomerular filtration rate (GFR, p = 0.035). Levels of 19 cytokines were higher, mainly in patients with acute gouty arthritis (p < 0.001), irrespective of the presence of the p.Q141K variant. The p.Q141K variant influences the age of onset of primary hyperuricemia or gout and other disease-linked risk factors and symptoms. There was no association with cytokine levels in the circulation.

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Novel insights into the role of inflammasomes in autoimmune and metabolic rheumatic diseases

Cited by 22 publications

References 70 publications

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

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

Immunopathogenic Mechanisms and Novel Immune-Modulated Therapies in Rheumatoid Arthritis

Interaction of the p.Q141K Variant of the ABCG2 Gene with Clinical Data and Cytokine Levels in Primary Hyperuricemia and Gout

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