Possible Implication of Red Blood Cells in the Prothrombotic Risk in Early Rheumatoid Arthritis

Franco, Manuela Di; Gambardella, Lucrezia; Lollo, Anna C hiara Di; Malorni, Walter; Valesini, Guido; Straface, Elisabetta

doi:10.3899/jrheum.141396

Cited by 4 publications

(11 citation statements)

References 10 publications

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“…Hypercoagulation, erythrocyte (RBC), and platelet involvement in RA as a result of systemic inflammation Another hallmark of systemic inflammation (as well as cardiovascular pathology) is clot hypercoagulability, and a hypercoagulable state is also found in RA, [222][223][224][225][226][227][228][229][230][231] together with a decreased clot lysis ability, 25,225,226 possibly due to genuine amyloid formation. 232 Systemic inflammation, oxidative stress, and hypercoagualability all affect erythrocytes (RBCs) and platelets.…”

Section: Pathophysiologic Markers Of Inflammation In Ramentioning

confidence: 99%

Major involvement of bacterial components in rheumatoid arthritis and its accompanying oxidative stress, systemic inflammation and hypercoagulability

Pretorius

Akeredolu

Soma

et al. 2016

Exp Biol Med (Maywood)

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We review the evidence that infectious agents, including those that become dormant within the host, have a major role to play in much of the etiology of rheumatoid arthritis and the inflammation that is its hallmark. This occurs in particular because they can produce cross-reactive (auto-)antigens, as well as potent inflammagens such as lipopolysaccharide that can themselves catalyze further inflammagenesis, including via β-amyloid formation. A series of observables coexist in many chronic, inflammatory diseases as well as rheumatoid arthritis. They include iron dysregulation, hypercoagulability, anomalous morphologies of host erythrocytes, and microparticle formation. Iron dysregulation may be responsible for the periodic regrowth and resuscitation of the dormant bacteria, with concomitant inflammagen production. The present systems biology analysis benefits from the philosophical idea of “coherence,” that reflects the principle that if a series of ostensibly unrelated findings are brought together into a self-consistent narrative, that narrative is thereby strengthened. As such, we provide a coherent and testable narrative for the major involvement of (often dormant) bacteria in rheumatoid arthritis.Impact statementRheumatoid arthritis (RA) is accompanied by long-term inflammation that is mediated by cytokines and cross-reactive (auto-)antigens. Here we suggest one explanation is the presence of a (dormant) microbiome in RA that sheds the highly potent inflammagen, lipopolysaccharide lipopolysaccharides (LPS) to catalyze inflammagenesis, including via β-amyloid formation. We discuss various co-existing features in RA, including iron dysregulation, hypercoagulability, anomalous morphologies of host erythrocytes, and microparticle formation. We review literature and provide coherent evidence that an aberrant blood microbiome in RA has a major involvement in the development, progression, and therefore over-all etiology of the disease.

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Section: Pathophysiologic Markers Of Inflammation In Ramentioning

confidence: 99%

Major involvement of bacterial components in rheumatoid arthritis and its accompanying oxidative stress, systemic inflammation and hypercoagulability

Pretorius

Akeredolu

Soma

et al. 2016

Exp Biol Med (Maywood)

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“…In addition, we found that this systemic oxidative imbalance did not seem to significantly interfere with the redox state of RBCs. In fact, compared to HD, in RBCs from RA patients, a mild increase of ROS/RNS level as well as a mild reduction of total thiol content was detected [12]. Moreover, no differences in the percentage of RBCs undergoing eryptosis, the programmed death of injured RBCs, were detected.…”

Section: Introductionmentioning

confidence: 80%

“…Surprisingly, a positive correlation was found between DAS28 score and ER-α content (r = 0.22). These results suggested that the expression of ER-α on the RBCs membrane of RA patients might be linked to the exogenous inflammatory and oxidative stress conditions and that these cells, due to the link between the estrogen receptor expression, the activation of intracellular signaling and the redox modulation [12,16], may become in turn source of reactive oxidizing species.…”

Section: Correlation Between Disease Activity Oxidative Stress and Er...mentioning

confidence: 99%

“…Moreover, no differences in the percentage of RBCs undergoing eryptosis, the programmed death of injured RBCs, were detected. Conversely, these cells showed a significant upregulation of survival molecules, such as survivin, as well as increased levels of the phosphorylated mitogen-activated protein kinase ERK 1/2 [12]. In addition, we recently demonstrated that estrogen receptors (ER- and ER-): i) were expressed by RBCs; ii) were both functionally active, iii) played a role in the modulation of RBCs intracellular signaling, and iv) modulated RBCs eNOS activation and NO release [16].…”

Section: Introductionmentioning

confidence: 96%

“…In a previous pilot study performed by our group, in view of their activity as redox effectors or "scavengers" as well as determinants in thrombus formation, we evaluated the redox state and lifespan molecules of RBCs isolated from RA patients investigating whether they were conditioned by systemic oxidative stress [12]. In this study we found that, compared to healthy donors (HD), plasma from RA patients showed increased MDA levels and decreased total antioxidant capacity (TAC) suggesting the occurrence of systemic oxidative stress as also reported in previous reports by other groups [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Estrogen Receptors, ERK 1/2 Phosphorylation and Reactive Oxidizing Species in Red Blood Cells From Patients With Rheumatoid Arthritis

Franco¹,

Gambardella²,

Cittadini³

et al. 2021

Preprint

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Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with a significantly increased risk of cardiovascular mortality, mainly attributed to accelerated atherosclerosis. Methods: Thirty-two women (aged more than 18 years) with RA, and 25 age-matched healthy women were included in this study. Biomarkers of inflammation, red blood cells (RBCs) redox balance, estrogen receptor alpha (ER-α) expression as well as ERK 1/2 phosphorylation content were evaluated in RA patients at baseline and six months after treatment with disease modifying anti‐rheumatic drugs (DMARDs). Results: For the first times we demonstrated that in RA patients: i) disease activity score (DAS-28) positively correlated with RBC ER-α expression, and negatively with total antioxidant capacity of plasma; ii) RBC ER-α expression positively correlated with systemic inflammatory biomarkers and oxidative stress parameters as well as ERK 1/2 phosphorylation; and iii) DMARDs treatments improved the clinical condition measured by DAS-28 score decrease, although the RBCs appeared to be more prone to pro-oxidant status associated to the expression of survival molecules. Conclusion: Our data strongly suggest that RBCs could also participate in vascular homeostasis through fine modulation of an intracellular signal linked to the ER-α.

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Platelets: emerging facilitators of cellular crosstalk in rheumatoid arthritis

et al. 2019

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Possible Implication of Red Blood Cells in the Prothrombotic Risk in Early Rheumatoid Arthritis

Cited by 4 publications

References 10 publications

Major involvement of bacterial components in rheumatoid arthritis and its accompanying oxidative stress, systemic inflammation and hypercoagulability

Major involvement of bacterial components in rheumatoid arthritis and its accompanying oxidative stress, systemic inflammation and hypercoagulability

Estrogen Receptors, ERK 1/2 Phosphorylation and Reactive Oxidizing Species in Red Blood Cells From Patients With Rheumatoid Arthritis

Platelets: emerging facilitators of cellular crosstalk in rheumatoid arthritis

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